Drug Repurposing News



Keytruda as standalone therapy for other cancers

June 15th 2017, Posted by: Drug Repurposing Portal

Ketruda, Developed by Merck, is a potent anti-PD-1 antibody that helps activate the immune system?s response to cancer cells. U.S. Food and Drug Administration had approved for the treatment of melanoma, lung. The Phase 2 KEYNOTE-059 trial is currently testing the efficacy of this anti-PD1 therapy as standalone treatment in patients with gastric or gastroesophageal junction adenocarcinoma who have not responded to two or more chemotherapy regimens. PD-L1 positive patients had an overall response rate to treatment of 15.5%. In contrast, only 6.4% of patients whose cancers did not expressed PD-L1 (109 patients) responded to Keytruda.


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Researchers aim to repurpose former experimental cancer therapy to treat muscular dystrophy

June 14th 2017, Posted by: Drug Repurposing Portal

Dr. Marugan at NCATS Chemical Genomics Center along with the team and collaborators, screened 350,000 compounds and identified SU9516 as a lead molecule that was used previously for the treatment of leukemia which could have potential utility in treatment for Duchenne muscular dystrophy (DMD). The research demonstrated that this compound improved muscle function in both laboratory and animal DMD models and the results were published recently in Journal of Molecular Therapy.


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ADA 2017: Investigational Drug for Knee Osteoarthritis Avoids Significant Rise in Blood Glucose in Type2 Diabetes Patients

June 13th 2017, Posted by: Drug Repurposing Portal

Flexion Therapeutics, Inc. presented data from a Phase II study which found its lead investigational drug candidate, FX006 (Zilretta) was associated with reduced blood glucose elevation compared with immediate release triamcinolone acetonide in crystalline suspension (TAcs) in patients with Type 2 diabetes and knee osteoarthritis (OA). FX006 was created to address the issue of the inadequate duration of the adequate pain relief associated with immediate relief steroids. Zilretta was formulated in such a way to achieve therapeutic concentrations or effective concentrations in the joint for three months and we demonstrated that we not only achieved longer relief which was the original goal, but pleasant surprise, Zilretta achieved better relief than seen with the immediate relief steroids?without the spike in blood glucose levels.


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Rituximab, re-purposed to ALS

June 8th 2017, Posted by: Drug Repurposing Portal

Rituximab is indicated to treat chronic lymphocytic leukemia, non-Hodgkin's lymphoma and rheumatoid arthritis. Scientists from Ben-Gurion University had successfully redesigned a portion of rituximab into a new molecule to treat ALS. In lab studies using mice, the therapy restored the immune cells of the central nervous system, which could potentially help extend survival in ALS patients.


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Doxycycline as repursed drug against parkinson's disease

May 23rd 2017, Posted by: Drug Repurposing Portal

In Parkinson's disease, Molecular triggers of inflammation are known to be targeted by Antibiotics. A study published in Scientific Reports found that a low dose of doxycycline was able to reduce the toxicity of &aplha;-synuclein, which aggregates to form amyloid fibrils the molecular trigger of inflammation in PD. The study concludes that, Doxycycline shows promise as repurposed drug against Parkinson's disease.


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Cancer drug Imatinib for severe asthma

May 19th 2017, Posted by: Drug Repurposing Portal

Imatinib is currently used to effectively treat cancers with specific mutation. Mechanism of action include, targeting mast cell development and stem cell factor the KIT receptor tyrosine kinase. In severe asthma, airways are infiltrated with mast cells and acts as an indicator of asthma. Researchers from Brigham and Women's Hospital had published in the New England Journal of Medicine that, targeting the mast cells with imatinib, improved airway hyperresponsiveness, a measure of the sensitivity of the airway, and decreased the number of mast cells present in the airway. Treatment also produced a small improvement in airway function. Researchers note that larger-scale studies are needed to confirm their finding and evaluate longer durations of therapy in order to definitively determine clinical efficacy.


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Multiple Sclerosis Drug Effectively Stops Mesothelioma Cells

May 13th 2017, Posted by: Drug Repurposing Portal

Research from the University of Hawaii Cancer Center shows an immune suppression drug, fingolimod (FTY720), which is already used to treat multiple sclerosis, could become an effective tool against malignant mesothelioma. The drug showed an ability to shrink mesothelioma tumors cells in the laboratory and in animal models without causing substantial side effects.


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Bavencio, An IO drug, by Pfizer and EMD Serono, gains approaval for Bladder Cancer Indication

May 12th 2017, Posted by: Drug Repurposing Portal

Bevanico gained approval in March for a rare form of skin cancer called Merkel Cell carcinoma. In less than two months, FDA had granted accelerated approval to Bavencio (avelumab) to treat patients with locally advanced or metastatic urothelial carcinoma, which is an aggressive form of bladder cancer that has a high rate of recurrence. The FDA made their decision after reviewing tumor response and response duration results from a phase 1 open-label study exploring Bavencio's safety and efficacy profiles with 242 patients diagnosed with this disease.


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One protein inhibitor could treat Chagas, leishmaniasis and sleeping sickness

May 10th 2017, Posted by: Drug Repurposing Portal

Wellcome Trust-backed scientists have found a compound that treats three neglected parasitic diseases in mice: leishmaniasis, Chagas disease and sleeping sickness. The Wellcome-funded team from the Novartis Research Foundation's Genomics Institute (GNF) focused on the genetic and biological similarities between the kinetoplastids, single-celled parasites.


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Translating GWAS Findings Into Therapies For Depression And Anxiety Disorders: Drug Repositioning Us

May 9th 2017, Posted by: Drug Repurposing Portal

Depression and anxiety disorders are the first and sixth leading cause of disability worldwide according to latest reports from the World Health Organization. Despite their high prevalence and the significant disability resulted, there are limited advances in new drug development. On the other hand, the advent of genome-wide association studies (GWAS) has greatly improved our understanding of the genetic basis underlying psychiatric disorders. In this work we employed gene-set analyses of GWAS summary statistics for drug repositioning. We explored five related GWAS datasets, including two on major depressive disorder (MDD-PGC and MDD-CONVERGE, with the latter focusing on severe depression cases), one on anxiety disorders, and two on depressive symptoms and neuroticism in the population. For example, the top repositioning hit using meta-analyzed p-values was fendiline, which was shown to produce antidepressant-like effects in mouse models by inhibition of acid sphingomyelinase and reducing ceramide levels. Taken together, our findings suggest that human genomic data such as GWAS might be useful in guiding drug discoveries for depression and anxiety disorders.


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Tofacitinib, An arthritis drug to treat moderate to severe ulcerative colitis

May 4th 2017, Posted by: Drug Repurposing Portal

Ulcerative colitis is a chronic inflammatory bowel disease. The illness causes inflammation, irritation, swelling and sores on the lining of the large intestine. New research lead by Dr. William Sandbornat finds that, Xeljanz targets certain proteins involved in the body's inflammatory and immune responses that other so-called biologic drugs don't. Thus Xeljanz, may relieve people with moderate to severe ulcerative colitis who haven't done well on other treatments.


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A structure- and chemical genomics-based approach for repositioning of drugs against VCP/p97 ATPase

April 25th 2017, Posted by: Drug Repurposing Portal

Valosin-containing protein (VCP/p97) ATPase (a.k.a. Cdc48) is a key member of the ER-associated protein degradation (ERAD) pathway. ERAD and VCP/p97 have been implicated in a multitude of human diseases, such as neurodegenerative diseases and cancer. Inhibition of VCP/p97 induces proteotoxic ER stress and cell death in cancer cells, making it an attractive target for cancer treatment. However, no drugs exist against this protein in the market. Repositioning of drugs towards new indications is an attractive alternative to the de novo drug development due to the potential for significantly shorter time to clinical translation. Here, we employed an integrative strategy for the repositioning of drugs as novel inhibitors of the VCP/p97 ATPase. We integrated structure-based virtual screening with the chemical genomics analysis of drug molecular signatures, and identified several candidate inhibitors of VCP/p97 ATPase. Importantly, experimental validation with cell-based and in vitro ATPase assays confirmed three (ebastine, astemizole and clotrimazole) out of seven tested candidates (~40% true hit rate) as direct inhibitors of VCP/p97 and ERAD. This study introduces an effective integrative strategy for drug repositioning, and identified new drugs against the VCP/p97/ERAD pathway in human diseases.


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Malaria experts set sights on single-shot cure by 2030s

April 25th 2017, Posted by: Drug Repurposing Portal

One of the objects of desire in the anti-malarial battle has been that some medicines already in use to treat other diseases could be repurposed to tackle malaria. Despite more than a decade looking for quick fixes from existing drugs, however, successes have been few and far between. The idea behind repurposing drugs had its modern-day genesis just before the turn of the millennium when the world?s armoury against malaria was bare. The most celebrated instance of a repurposed or crossover drug is the case of ivermectin, designed to kill the parasites that cause river blindness and filariasis, also known as elephantiasis. Researchers at Colorado State University in 2015 found that administering the drug en masse helped reduce malaria episodes in some areas of west Africa. A separate study by the US Army found the drug helped block development of Plasmodium vivax parasites in mosquitoes most commonly found in Asia.


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Global Drug Repurposing Market to Witness a Pronounce Growth During 2017 to 2025

April 25th 2017, Posted by: Drug Repurposing Portal

Drug repurposing or re-profiling has been the hallmark to bring strong business growth and the trend is being followed by majority of the pharmaceutical and biopharmaceutical companies. Among all biologics approved in the U.S. during 2007-2009, 30-40% of them were the drugs repurposed or repositioned. National Institute of Health (NIH), U.S. Department of Health defines drug repurposing as discovering new uses for approved drugs to provide the quickest possible transition from bench to bedside. Drug repurposing opens up various opportunities to answer current unmet medical needs to come up with cost-effective solutions to expensive drug development process.


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Repurposed drugs targeting eIF2α-P-mediated translational repression prevent neurodegeneration in m

April 24th 2017, Posted by: Drug Repurposing Portal

NINDS small molecule library of 1040 drugs was used to perform phenotypic screnning and looking at anti-eIF2α-P activity suitable for clinical use. The researchers found trazodone hydrochloride and dibenzoylmethane with maximum potenital, which reversed eIF2α-P-mediated translational attenuation in vitro and in vivo. Both drugs were markedly neuroprotective in two mouse models of neurodegeneration, using clinically relevant doses over a prolonged period of time, without systemic toxicity.


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Filling the gap in CNS drug development: evaluation of the role of drug repurposing

April 24th 2017, Posted by: Drug Repurposing Portal

Drug repurposing has been considered a cost-effective and reduced-risk strategy for developing new drugs. Little is known and documented regarding the efficiency of repurposing strategies in drug development. The objective of this article is to assess the extent and meaning of this process in the CNS area.


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Scientists discover two repurposed drugs that arrest neurodegeneration in mice

April 22nd 2017, Posted by: Drug Repurposing Portal

A team of researchers tested 1,040 compounds and identified two drugs that restored protein production rates in mice, trazodone hydrochloride, a licensed antidepressant, and dibenzoylmethane, a compound being trialled as an anti-cancer drug. Both drugs prevented the emergence of signs of brain cell damage in most of the prion-diseased mice and restored memory in the FTD mice. In both mouse models, the drugs reduced brain shrinkage which is a feature of neurodegenerative disease.


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Accelerating Precision Drug Development and Drug Repurposing by Leveraging Human Genetics

April 21st 2017, Posted by: Drug Repurposing Portal

The potential impact of using human genetic data linked to longitudinal electronic medical records on drug development is extraordinary; however, the practical application of these data necessitates some organizational innovations. Vanderbilt has created resources such as an easily queried database of >2.6 million de-identified electronic health records linked to BioVU, which is a DNA biobank with more than 230,000 unique samples. To ensure these data are used to maximally benefit and accelerate both de novo drug discovery and drug repurposing efforts, we created the Accelerating Drug Development and Repurposing Incubator, a multidisciplinary think tank of experts in various therapeutic areas within both basic and clinical science as well as experts in legal, business, and other operational domains. The Incubator supports a diverse pipeline of drug indication finding projects, leveraging the natural experiment of human genetics.


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Heter-LP: A heterogeneous label propagation algorithm and its application in drug repositioning

April 20th 2017, Posted by: Drug Repurposing Portal

Drug repositioning offers an effective solution to drug discovery, saving both time and resources by finding new indications for existing drugs. Typically, a drug takes effect via its protein targets in the cell. As a result, it is necessary for drug development studies to conduct an investigation into the interrelationships of drugs, protein targets, and diseases. Although previous studies have made a strong case for the effectiveness of integrative network-based methods for predicting these interrelationships, little progress has been achieved in this regard within drug repositioning research. Moreover, the interactions of new drugs and targets (lacking any known targets and drugs, respectively) cannot be accurately predicted by most established methods. In this paper, we propose a novel semi-supervised heterogeneous label propagation algorithm named Heter-LP, which applies both local and global network features for data integration. To predict drug-target, disease-target, and drug-disease associations, we use information about drugs, diseases, and targets as collected from multiple sources at different levels. Our algorithm integrates these various types of data into a heterogeneous network and implements a label propagation algorithm to find new interactions. Statistical analyses of 10-fold cross-validation results and experimental analyses support the effectiveness of the proposed algorithm.


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Mesothelioma shows promising response to existing immunotherapy drug

April 19th 2017, Posted by: Drug Repurposing Portal

Mesothelioma is a rare cancer that arises in the thin lining of tissue that covers the inside of the chest, the heart, the abdomen, and most internal organs. The main risk factor for mesothelioma is inhalation of asbestos. Dr. Evan Alley and his colleagues, University of Pennsylvania Health System in Philadelphia, has found a new class of drugs, checkpoint inhibitors. Checkpoint inhibitors are drugs designed to help the body fight cancer by defeating certain mechanisms that cancer cells use to avoid being attacked by the immune system. Pembrolizumab is one such drug. Pembrolizumab is already used to treat non-small cell lung cancer, melanoma, and some head and neck cancers. New results show that Pembrolizumab lead to tumour shrinkage in mesothelioma patients after treatment.


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Could antidepressants stop prostate cancer from spreading?

April 19th 2017, Posted by: Drug Repurposing Portal

Jason Wu, of Washington State University-Spokane, and colleagues found that a drug called clorgyline - a drug once used as an antidepressant can control the growth of prostate cancer cell's. Clorgyline is known to block the activity of MAOA, an enzyme that prompts a signaling cascade that simplifies the process by which prostate cancer cells spread to the bone. Researchers found that the drug prevented MAOA from activating the three proteins that enhance osteoclast function, thereby reducing the prostate cancer cell's ability to invade and grow in bone.


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Identifying new antiepileptic drugs through genomics-based drug repurposing

April 19th 2017, Posted by: Drug Repurposing Portal

Currently available antiepileptic drugs (AEDs) fail to control seizures in 30% of patients. Genomics-based drug repurposing (GBR) offers the potential of savings in the time and cost of developing new AEDs. In the current study, we used published data and software to identify the transcriptomic signature of chornic temporal lobe epilepsy and the drugs that reverse it. After filtering out compounds based on exclusion criteria, such as toxicity, 36 drugs were retained. 11 of the 36 drugs identified (>30%) have published evidence of the antiepileptic efficacy (for example, curcumin) or antiepileptogenic affect (for example, atorvastatin) in recognised rodent models or patients. By objectively annotating all 20,000 compounds in the LINCS database as either having published evidence of antiepileptic efficacy or lacking such evidence, we demonstrated that our set of repurposable drugs is 6-fold more enriched with drugs having published evidence of antiepileptic efficacy in animal models than expected by chance (P-value<0.006). Further, we showed that another of our GBR-identified drugs, the commonly-used well-tolerated antihyperglycemic sitagliptin, produces a dose-dependent reduction in seizures in a mouse model of pharmacoresistant epilepsy. In conclusion, GBR successfully identifies compounds with antiepileptic efficacy in animal models and, hence, it is an appealing methodology for the discovery of potential AEDs.


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Some Remarks on Prediction of Drug-Target Interaction with Network Models.

April 18th 2017, Posted by: Drug Repurposing Portal

System-level understanding of the relationships between drugs and targets is very important for enhancing drug research, especially for drug function repositioning. The experimental methods used to determine drug-target interactions are usually time-consuming, tedious and expensive, and sometimes lack reproducibility. Thus, it is highly desired to develop computational methods for efficiently and effectively analyzing and detecting new drug-target interaction pairs. With the explosive growth of different types of omics data, such as genome, pharmacology, phenotypic, and other kinds of molecular networks, numerous computational approaches have been developed to predict drug-target interactions (DTI). In this review, we make a survey on the recent advances in predicting drug-target interaction with network-based models from the following aspects: i) Available public data sources and benchmark datasets, ii) Drug/target similarity metrics, iii) Network construction, iv) Common network algorithms, v) Performance comparison of existing network-based DTI predictors.


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Use of antiparasitic drug as new treatment for brain tumors explored by researchers

April 18th 2017, Posted by: Drug Repurposing Portal

A team of researchers led by Dr. Symons from the Feinstein Institute for Medical Research's Karches Center for Oncology Research has recently found that mebendazole, a medication that is used to treat parasitic pinworms, is effective in the treatment of glioma tumors. The study results have recently been published in journal Molecular Medicine.


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Orphan Drugs Market Growing at a CAGR of 10.20% During 2017 to 2021, Says a New Report at ReportsnR

April 17th 2017, Posted by: Drug Repurposing Portal

One trend in orphan drugs market is repurposing of non-orphan drugs to orphan drugs. The orphan drugs market has witnessed many successful repositioning of drugs from non-orphan label to orphan label. Since the implementation of the orphan drug legislation in the United States, more than 69 drugs which were first approved by US FDA for the treatment of rare diseases were not entirely new and had been repurposed from the non-orphan label to the orphan label. Today, most of the pharmaceutical and biotechnological companies have adopted the strategy of drug repurposing in order to save time and money. Repurposing of an already approved drug for a different indication helps to mitigate the risk of drug failure as the drug has undergone the pharmacovigilance regulatory requirement and post-marketing survey. This reduces the risk of heavy financial loss to the manufacturer. In addition, the drug repurposing strategy also helps manufacturers to extend their product life cycle by getting orphan drug status, and also prevents their product from generic competition.


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NuMedii, Inc. Announces New Partnership To Discover And Advance New Treatments For Idiopathic Pulmon

April 13th 2017, Posted by: Drug Repurposing Portal

NuMedii & Three Lakes Partners, LLC enter into a collaboration in the pursuit of identifying therapies for idiopathic pulmonary fibrosis (IPF) based on NuMedii's Big Data intelligence technology. NuMedii's CEO, Gini Deshpande says "This unique partnership between an AI drug discovery company and a patient-centric organization further builds on our work in inflammation and showcases our progress, particularly our development capabilities in rare disease."


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The Drug Repurposing Hub: a next-generation drug library and information resource

April 11th 2017, Posted by: Drug Repurposing Portal

An online repurposing library, drug Repurposing Hub b (http:// www.broadinstitute.org/repurposing) contains hand-curated a collection of 4,707 compounds with experimentally confirmed their identities and annotated with literature-reported targets. The collection includes 3,422 drugs that are marketed around the world or that have been tested in human clinical trials.


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A Biologically-Based Computational Approach to Drug Repurposing for Anthrax Infection

April 11th 2017, Posted by: Drug Repurposing Portal

Developing drugs to treat the toxic effects of lethal toxin (LT) and edema toxin (ET) produced by B. anthracis is of global interest. We utilized a computational approach to score 474 drugs/compounds for their ability to reverse the toxic effects of anthrax toxins. For each toxin or drug/compound, we constructed an activity network by using its differentially expressed genes, molecular targets, and protein interactions. Gene expression profiles of drugs were obtained from the Connectivity Map and those of anthrax toxins in human alveolar macrophages were obtained from the Gene Expression Omnibus. Drug rankings were based on the ability of a drug/compound's mode of action in the form of a signaling network to reverse the effects of anthrax toxins; literature reports were used to verify the top 10 and bottom 10 drugs/compounds identified. Simvastatin and bepridil with reported in vitro potency for protecting cells from LT and ET toxicities were computationally ranked fourth and eighth. The other top 10 drugs were fenofibrate, dihydroergotamine, cotinine, amantadine, mephenytoin, sotalol, ifosfamide, and mefloquine; literature mining revealed their potential protective effects from LT and ET toxicities. These drugs are worthy of investigation for their therapeutic benefits and might be used in combination with antibiotics for treating B. anthracis infection.


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Network-based analysis of transcriptional profiles from chemical perturbations experiments

April 11th 2017, Posted by: Drug Repurposing Portal

A pipeline for analyzing transcriptional network inference and comparison for grouping chemicals with similar functions and carcinogenicity / genotoxicity profiles. In the context of drug discovery or drug repositioning, discussed method could help assign new functions to novel or existing drugs, based on the similarity of their associated network with those built for other known compounds. Additionally, the method has broad applicability beyond the uses here described and could be used as an alternative or as a complement to standard approaches of differential gene expression analysis.


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A one-two punch hits pancreatic cancer where it hurts

April 10th 2017, Posted by: Drug Repurposing Portal

Australian scientists have uncovered a promising new approach to treating pancreatic cancer, by targeting the tissue around the tumour to make it 'softer' and more responsive to chemotherapy with a three-day course of Fasudil, which is an inhibitor of the protein ROCK and approved for the treatment of cerebral vasospasm. The findings are recently published in Science Translational Medicine.


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Systematic drug repositioning through mining adverse event data in ClinicalTrials.gov

April 6th 2017, Posted by: Drug Repurposing Portal

Drug repositioning (i.e., drug repurposing) is the process of discovering new uses for marketed drugs. Historically, such discoveries were serendipitous. However, the rapid growth in electronic clinical data and text mining tools makes it feasible to systematically identify drugs with the potential to be repurposed. Described here is a novel method of drug repositioning by mining ClinicalTrials.gov. The text mining tools I2E (Linguamatics) and PolyAnalyst (Megaputer) were utilized. An I2E query extracts "Serious Adverse Events" (SAE) data from randomized trials in ClinicalTrials.gov


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Sh100 malaria drug could be used to manage colon cancer

April 6th 2017, Posted by: Drug Repurposing Portal

A team of researchers from two institutions in the United Kingdom, St George's University of London and St George's Hospital, have demonstrated that artesunate, a common and cheap oral malaria drug that costs less than Sh100, reduces the multiplication of tumour cells and the chance of colorectal cancer spreading or recurring after surgery.


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Senicapoc: Repurposing a Drug to Target Microglia KCa3.1 in Stroke

April 6th 2017, Posted by: Drug Repurposing Portal

Stroke is the leading cause of serious long-term disability and the fifth leading cause of death in the United States. Treatment options for stroke are few in number and limited in efficacy. Neuroinflammation mediated by microglia and infiltrating peripheral immune cells is a major component of stroke pathophysiology. Interfering with the inflammation cascade after stroke holds the promise to modulate stroke outcome. The calcium activated potassium channel KCa3.1 is expressed selectively in the injured CNS by microglia. KCa3.1 function has been implicated in pro-inflammatory activation of microglia and there is recent literature suggesting that this channel is important in the pathophysiology of ischemia/reperfusion (stroke) related brain injury. Here we describe the potential of repurposing Senicapoc, a KCa3.1 inhibitor, to intervene in the inflammation cascade that follows ischemia/reperfusion.


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Laying in silico pipelines for drug repositioning: a paradigm in ensemble analysis for neurodegenera

April 6th 2017, Posted by: Drug Repurposing Portal

When faced with time- and money-consuming problems, new practices in pharmaceutical R&D arose when trying to alleviate them. Drug repositioning has great promise and when combined with today's computational power and intelligence it becomes more precise and potent. This work showcases current approaches of creating a computational pipeline for drug repositioning, along with an extensive example of how researchers can influence therapeutic approaches and further understanding, through either single or multiple disease studies. This paradigm is based on three neurodegenerative diseases with pathophysiological similarities. It is our goal to provide the readers with all the information needed to enrich their research and note expectations along the way.


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Repurposed Diabetes Drug Shows Promise as Breast Cancer Treatment

April 6th 2017, Posted by: Drug Repurposing Portal

According to a study published by the journal of experimental medicine, an approved diabetes drug, epalrestat, which is an AKR1B1 inhibitor, may be able to prevent metastasis in patients with aggressive, basal-like triple-negative breast cancer. In this study, authors discovered that basal-like triple-negative breast cancers had high levels of AKR1B1 expression, which was linked to high rates of metastasis and poor patient outcomes.


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Repurposing 2 autoimmune drugs for chikungunya virus

April 5th 2017, Posted by: Drug Repurposing Portal

It has been demonstrated by Teck-Hui Teo and team that chikungunya virus infected mice given multiple sclerosis therapy Fingolimid, which prevents T cells from leaving the lymph nodes, experienced less joint inflammation. Corroborating these results further, Jonathan Miner and colleagues found that the rheumatoid arthritis drug Abatacept, which hinders T cell activation in the lymph nodes, decreased inflammation in the joints of infected mice, and abolished arthritis completely when given in combination with an antibody targeting the virus.


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IntelGenx Presents at the 13th International Conference on Alzheimer's and Parkinson's Diseases

April 5th 2017, Posted by: Drug Repurposing Portal

IntelGenx Technologies Corp, a leading oral drug delivery company presented its current research findings on repurposing Montelukast; an FDA approved Asthma drug for the treatment of Alzheimer's disease. IntelGenx?s proprietary Versafilm Technology platform improves the bioavailability of Montelukast rendering an enhanced blood brain barrier penetrance in a Phase I study conducted. The drug with its leukotriene receptor antagonistic action, might be effective in restoring brain cell function via reducing neuro-inflammation and the efficacy needs to be further demonstrated in a Phase II trial.


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Drug repurposing for castration resistant prostate cancer based on disease-disease rel

April 5th 2017, Posted by: Drug Repurposing Portal

Prostate cancer (PCa) ranks second in terms of cancer-related deaths among men in the United States. The primary cause is the emergence of castration resistant prostate cancer (CRPC) and subsequent metastasis and chemoresistance. There is no known cure for CRPC with a median survival rate of about 18 months. CRPC tumors are either intrinsically resistant or rapidly develop resistance to chemotherapy. Traditional approaches to drug discovery are highly specific to single targets (molecules and indications) and are time-consuming trial-and-error approaches, which are often ineffective and unsafe for humans. This approach has resulted in a dearth of novel drugs (currently less than thirty are approved each year) and the time and costs to develop and bring one to market are prohibitive ($2.6 billion in 2013). A solution is to repurpose existing drugs with known safety profiles that interact with therapeutic targets and can be rapidly deployed for use in mono and multi-drug therapies. However, there is a problem in consistently identifying high-confidence drugs for CRPC. Many computational tools have been developed for analyses of high-throughput genomics data, and these methods have led to improved understanding of cancer biology. However, despite the generation of enormous amounts of data, improved treatments and diagnostics take a long time, and a substantial amount of research is needed to translate a genomic discovery to the bedside. We have developed an integrated drug discovery/repurposing platform that analyzes compound-protein structural interaction signatures across multiple proteomes to determine drug behavior, in contrast to traditional single (or few) target approaches. The platform implements a modeling pipeline that generates an interaction between "all" (currently 3,733) human approved drugs and "all" (currently 48,278) proteins using our interactome docking with dynamics program to compute ~ 1 billion proteome-compound interactions. We have prospectively validated our predictions with in vitro and in vivo preclinical studies for more than 10 different diseases including immunological, metabolic, infectious and genetic indications. Recently, we applied our integrated drug discovery pipeline and found strong relationship between CRPC with breast cancer, hypertension and inflammation to repurpose human approved drugs for CRPC. We have newly identified an FDA approved drug with IC50 less than 10nM activity on LnCaP and C4-2 cell proliferation. The repurposed lead is tissue specific and its toxicity is very less compared to other chemotherapeutic agents used for cancer. Using our computational design approach of taking into account target and anti-target binding profile we are modifying and synthesizing new analogues of this potent anti-cancer human approved drug for immunomodulation without effecting anti-cancer potency. We conclude that compared to traditional single target drug discovery that is slow and error prone, interactome based d


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Mendelian randomization: a novel approach for the prediction of adverse drug events and drug repurposing

April 5th 2017, Posted by: Drug Repurposing Portal

Identification of unintended drug effects, specifically drug repurposing opportunities and adverse drug events, maximizes the benefit of a drug and protects the health of patients. However, current observational research methods are subject to several biases. These include confounding by indication, reverse causality, and missing data. We propose that Mendelian randomization (MR) offers a novel approach for the prediction of unintended drug effects. In particular, we advocate the synthesis of evidence from this method and other approaches, in the spirit of triangulation, to improve causal inferences concerning drug effects. MR overcomes some of the limitations associated with the existing methods in this field. Furthermore, it can be applied either pre- or post-approval of the drug and could therefore prevent the potentially harmful exposure of patients in clinical trials and beyond. The potential of MR as a pharmacovigilance and drug repurposing tool is yet to be realized and could both help prevent adverse drug events and identify novel indications for existing drugs in the future.


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Interferon Drug Shows Promise in Treating Ebola

April 4th 2017, Posted by: Drug Repurposing Portal

Interferon β-1a, used to treat hepatitis and some forms of multiple sclerosis has been shown for the first time to ease symptoms of Ebola patients in a pilot study conducted in 9 individuals with Ebola virus. The results were compared retrospectively with a matched cohort of 21 infected individuals receiving standardized supportive care only during the same time period at the same treatment centre in Guinea. 67 per cent of the interferon-treated patients were still alive at 21 days in contrast to 19 per cent of the former patients. Additionally, the viral blood clearance was faster in those patients treated with Interferon β-1a. Many clinical symptoms such as abdominal pain, vomiting, nausea and diarrhea were also relieved earlier in the interferon-treated patients.


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Computational Discovery of Niclosamide Ethanolamine, A Repurposed Drug Candidate That Reduces Growth

April 3rd 2017, Posted by: Drug Repurposing Portal

Drug repositioning offers a shorter approval process than new drug development. The article describes large public datasets search for drug-induced gene expression signatures to identify agents that might be effective against hepatocellular carcinoma (HCC).


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Biomedical Catalyst: Developmental Pathway Funding Scheme (DPFS): Mar 2017

March 16th 2017, Posted by: Drug Repurposing Portal

The DPFS scheme is a key part of our Translational Research Strategy and supports the translation of fundamental discoveries toward benefits to human health. It funds the pre-clinical development and early clinical testing of novel therapeutics, devices and diagnostics, including ?repurposing? of existing therapies. The scheme supports academically led projects whose goals are to improve prevention, diagnosis, prognosis, or treatment of significant health needs, or that focus on developing research tools that increase the efficiency of developing interventions.


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Drug repurposing screen identifies lestaurtinib amplifies the ability of the poly (ADP-ribose) polymerase 1 inhibitor AG14361 to kill breast cancer associated gene-1 mutant and wild type breast cancer cells

March 16th 2017, Posted by: Drug Repurposing Portal

Lestaurtinib, which is an orally bioavailable multikinase inhibitor that has been used in clinical trials for myeloproliferative disorders and acute myelogenous leukemia, enhanced the activity of the potent PARPi AG14361 on breast cancer cell growth both in vitro and in vivo conditions. Lestaurtinib amplifies the ability of the PARP1 inhibitor AG14361 to kill BRCA1 mutant and wild-type breast cancer cells, at least in part, by inhibiting NF-?B signaling. Each of these drugs has been approved for several different cancers, and their combination treatment should be applicable for a breast cancer trial in the future.


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Bowel cancer medication could help combat early-onset Parkinson's disease

March 14th 2017, Posted by: Drug Repurposing Portal

A study, which has been published in Science Matters, suggests that folinic acid, which is used in medications to treat bowel cancer, can also protect neurons associated with Parkinson's disease in fruit flies.


News Methods Funding Collaborations

A standard database for drug repositioning

March 14th 2017, Posted by: Drug Repurposing Portal

A gold standard database, repoDB, that consists of both true positives (approved drugs), and true negatives (failed drugs) developed by Adam Brown and colleagues at Biomedical Department of Harvard Medical School. The team has made the full database and all code used to prepare it publicly available, and have developed a web application that allows users to browse subsets of the data. This could be accessed at- http://apps.chiragjpgroup.org/repoDB.


News Methods Funding Collaborations

Deep-Learning-Based Drug-Target Interaction Prediction

March 13th 2017, Posted by: Drug Repurposing Portal

Wen and team from Central South University & Chinese Academy of Tropical Agricultural Sciences-China, have found a method to accurately predict new drug-target interactions (DTIs) between approved drugs and targets without separating the targets into different classes. The group has developed a deep-learning-based algorithmic framework named DeepDTIs which can be further used to predict whether a new drug targets to some existing targets or whether a new target interacts with some existing drugs.


News Methods Funding Collaborations

Non-kinase targets of protein kinase inhibitors

March 10th 2017, Posted by: Drug Repurposing Portal

Kinome-wide profiling platforms have comprehensively identified the relevant kinases that are targeted by numerous protein kinase inhibitors. However, recent projects have begun to discover non-kinase targets of kinase inhibitors. These non-kinase targets can contribute to the desired or undesired activities of inhibitors, or act as silent bystanders. As a full awareness of a drug's mechanism of action is crucial for the interpretation of results and for successful preclinical and clinical drug development, these discoveries highlight the importance of understanding the pharmacology of kinase inhibitors beyond the kinome. In this Review, I discuss kinase inhibitors for which non-kinase targets have been identified and the application of emerging techniques to validate drug?target engagement in intact cells.


News Methods Funding Collaborations

In vitro screening of an FDA-Approved Library against ESKAPE pathogens

March 9th 2017, Posted by: Drug Repurposing Portal

In an effort to repurpose drugs and explore new leads in the field of antimicrobial drug discovery, Younis et al at Purdue University College of Veterinary Medicine performed a whole-cell screening assay of 1,600 Food and Drug Administration (FDA) approved drugs against Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae (ESKAPE) pathogens. The in vitro screening identified 49 non-antimicrobial drugs that were active against at least one species of ESKAPE pathogen. Although some of these drugs were known to have antibacterial activity, many have never been reported before and Sulfonamide based structures were proposed for further investigation.


News Methods Funding Collaborations

Arthritis Drug Could Give Chemotherapy More Punch Against Triple-Negative Breast Cancer

March 8th 2017, Posted by: Drug Repurposing Portal

A combination of FDA approved drug for rheumatoid arthritis; leflunomide and Adriamycin effectively reduced the tumor volume in TNBC mice models compared to the treatment with both the drugs alone in a study conducted by Toker from Cancer Center at Beth Israel Deaconess Medical Center in Boston. A clinical trial is planned to test the efficacy and safety of these two drugs, suggesting a new drug repurposing treatment strategy for TNBC patients.


News Methods Funding Collaborations

Teaching old drugs new tricks - drug repurposing for rare disease

February 28th 2017, Posted by: Drug Repurposing Portal

Rick Thompson at FindACure provides a 360 degree overview on the drug repurposing space for Rare Disease. Topics covered include, how challenging it is to find a treatment for a given rare disease, what exists out there in the space in terms of medical options for patients, how drug repurposing helps here to identify opportunities to treat such devastating disease conditions and some success stories that the organization (FindACure) has identified.


News Methods Funding Collaborations

Identifying New Antiepileptic Drugs Through Genomics-Based Drug Repurposing

February 28th 2017, Posted by: Drug Repurposing Portal

Dr. Nasir Mirza, et al at the University of Liverpool has been able to identify new leads as potential treatment options for Epilepsy. The team is conducting a webinar on the results from their study where they have been able to implement GBR (genomics based drug repurposing) and identify 36 lead compounds to control seizures in patients.


News Methods Funding Collaborations

Construction of an miRNA-regulated drug-pathway network reveals drug repurposing candidates for myasthenia gravis

February 28th 2017, Posted by: Drug Repurposing Portal

Myasthenia gravis (MG) is a rare debilitating autoimmune neuromuscular disorder. Many studies have focused on the mechanism and treatment strategies of MG. However, the exact pathogenesis of MG and effective treatment strategies remain unclear. Recent studies have indicated that microRNAs (miRNAs or miRs) can regulate the pathological pathways of MG, suggesting their potential role in novel treatments. In the present study, the authors created a comprehensive catalog of experimentally confirmed MG risk genes and miRNAs by manually mining published literature and public databases. Based on these genes and miRNAs, they identified 41?MG risk pathways and 105?approved drugs that can affect these pathways. Some important MG-related pathways, such as hsa04060 (cytokine-cytokine receptor interaction) and hsa05200 (pathway in cancer), were found to be regulated by MG risk miRNAs and drugs. Furthermore, they constructed an miRNA-regulated drug-pathway network and identified miRNAs and drugs that synergistically regulate key MG pathways and biological processes. They developed a drug repurposing strategy to identify 25?drug repurposing candidates for MG; several of these drugs, such as rituximab, adalimumab, sunitinib, and muromonab, have the potential to be novel MG treatment drugs. This study provides novel insight into the pathogenesis of MG and potential drug candidates for MG were identified.


News Methods Funding Collaborations

Drug voyager: a computational platform for exploring unintended drug action

February 28th 2017, Posted by: Drug Repurposing Portal

This study addresses how we can computationally represent drug-signaling pathways to understand unintended drug actions and to facilitate drug discovery and screening. This is ?a novel platform to construct a drug-specific pathway in which a molecular-level mechanism of action is formulated based on pharmacologic, pharmacogenomic, transcriptomic, and phenotypic data related to drug response ( http://databio.gachon.ac.kr/tools/ )


News Methods Funding Collaborations

Computational Multitarget Drug Design

February 23rd 2017, Posted by: Drug Repurposing Portal

An overview of recent progress on finding drugs that can hit multiple targets for a complex disease. Such approach takes in to account features of both ligand and its different receptors. On successful application, these drugs have the potential to replace or reduce the requirements of multi-drug therapy.


News Methods Funding Collaborations

A Systematic Framework for Drug Repositioning from Integrated Omics and Drug Phenotype Profiles Using Pathway-Drug Network

February 23rd 2017, Posted by: Drug Repurposing Portal

Drug repositioning offers new clinical indications for old drugs. Recently, many computational approaches have been developed to repurpose marketed drugs in human diseases by mining various of biological data including disease expression profiles, pathways, drug phenotype expression profiles, and chemical structure data. However, despite encouraging results, a comprehensive and efficient computational drug repositioning approach is needed that includes the high-level integration of available resources. In this study, we propose a systematic framework employing experimental genomic knowledge and pharmaceutical knowledge to reposition drugs for a specific disease. Specifically, we first obtain experimental genomic knowledge from disease gene expression profiles and pharmaceutical knowledge from drug phenotype expression profiles and construct a pathway-drug network representing a priori known associations between drugs and pathways. To discover promising candidates for drug repositioning, we initialize node labels for the pathway-drug network using identified disease pathways and known drugs associated with the phenotype of interest and perform network propagation in a semi-supervised manner. To evaluate our method, we conducted some experiments to reposition 1309 drugs based on four different breast cancer datasets and verified the results of promising candidate drugs for breast cancer by a two-step validation procedure. Consequently, our experimental results showed that the proposed framework is quite useful approach to discover promising candidates for breast cancer treatment.


News Methods Funding Collaborations

Human enterovirus 71 protein interaction network prompts antiviral drug repositioning

February 21st 2017, Posted by: Drug Repurposing Portal

Lu et al of Beijing Institute of Radiation Medicine used a combination of experimental and computational approaches to identify interactions between EV71 proteins and host cellular proteins and confirmed the functional relationships of EV71-interacting proteins (EIPs) with virus proliferation and infection by integrating a human protein interaction network and by functional annotation. The team predicted tanespimycin as a candidate and demonstrated its antiviral efficiency in vitro. These findings provide the first systematic identification of EV71-host protein interactions, an analysis of EIP protein characteristics and a demonstration of their value in developing host-oriented antiviral therapies.


News Methods Funding Collaborations

Systematic analyses of drugs and disease indications in RepurposeDB reveal pharmacological, biological and epidemiological factors influencing drug repositioning

February 15th 2017, Posted by: Drug Repurposing Portal

Drug repositioning, the discovery of new or improved therapies by reevaluation of approved or investigational compounds, solves a significant gap in the public health setting and improves the productivity of drug development. Increase in global population and growing disease burden due to the emergence of infectious diseases (Zika virus), multidrug-resistant pathogens, drug-resistant cancers (cisplatin-resistant ovarian cancer) and chronic diseases (arterial hypertension) necessitate effective therapies to improve health outcomes. Collectively, RepurposeDB is developed as the reference database for drug repositioning investigations. The pharmacological, biological and epidemiological principles of drug repositioning identified from the meta-analyses could augment therapeutic development


News Methods Funding Collaborations

NCATS Seeks Applications to Repurpose Existing Drugs

February 15th 2017, Posted by: Drug Repurposing Portal

In collaboration with AstraZeneca and Janssen Research & Development, LLC, NCATS is seeking applications through its NIH-Industry Partnerships initiative to explore new treatments for patients, using existing experimental drugs or biologics. NCATS plans to commit an estimated $6 million to fund six to 10 awards to support partnerships between the pharmaceutical companies and the biomedical research community by making a selection of industry assets available to test ideas for new therapeutic uses.


News Methods Funding Collaborations

German Biotech gets Seed Funding to Repurpose Cancer Drugs for the Flu

February 8th 2017, Posted by: Drug Repurposing Portal

Atriva Therapeutics was founded in T?bingen, Germany in 2015 with a quite particular aim: repurposing cancer drugs to treat influenza. Two private investors, the Dutch Stichting Participatie Atriva and the German High-Tech Gr?nderfonds (HTGF) have contributed with an undisclosed amount of seed funding that will help the young biotech push its first drug candidate to the clinic. Atriva?s lead candidate, ATR-002, is expected to enter clinical trials in 2018. The drug is intended for treating influenza in high-risk patients with severe respiratory complications due to bacterial co-infections


News Methods Funding Collaborations

Brain Tumor Cells Sensitive to FDA-approved Ovarian Cancer Drug, Study Finds

February 3rd 2017, Posted by: Drug Repurposing Portal

Oaparib, a PARP inhibitor already approved for ovarian cancer treatment showed a 50 fold increased death of brain tumor cells with IDH1 and IDH2 gene mutations in a study conducted by scientists from Yale University. A clinical trial study for repurposing drugs like oaparib for the treatment of brain tumors is also planned by the team in future.


News Methods Funding Collaborations

A Pinworm Medication Is Being Tested As A Potential Anti-Cancer Drug

January 30th 2017, Posted by: Drug Repurposing Portal

Cancer researchers are testing whether a generic drug that has been used for more than 40 years to treat parasitic infections may also help fight cancer. The tests of mebendazole are part of a growing effort to take a fresh look at old medicines to see if they can be repurposed for new uses. Gregory Riggins, a researcher at Johns Hopkins University, discovered that laboratory mice didn't develop cancer after being given a drug for pinworms.


News Methods Funding Collaborations

DeSigN: connecting gene expression with therapeutics for?drug repurposing?and development

January 25th 2017, Posted by: Drug Repurposing Portal

The?drug?discovery and development pipeline is a long and arduous process that inevitably hampers rapid?drug?development. Therefore, strategies to improve the efficiency of?drug?development are urgently needed to enable effective drugs to enter the clinic. Precision medicine has demonstrated that genetic features of cancer cells can be used for predicting?drug?response, and emerging evidence suggest that gene-drug?connections could be predicted more accurately by exploring the cumulative effects of many genes simultaneously.


News Methods Funding Collaborations

Pharmacophore-based screening and drug repurposing exemplified on glycogen synthase kinase-3 inhibitors

January 21st 2017, Posted by: Drug Repurposing Portal

Study by Crisan et al elaborate a novel pharmacophore model to accurately map selective glycogen synthase kinase-3 (GSK-3) inhibitors, and perform virtual screening and drug repurposing. Pharmacophore modeling was developed using PHASE on a data set of 203 maleimides. Two benchmarking validation data sets with focus on selectivity were assembled using ChEMBL and PubChem GSK-3 confirmatory assays. A drug repurposing experiment linking pharmacophore matching with drug information originating from multiple data sources was performed. A five-point pharmacophore model was built consisting of a hydrogen bond acceptor (A), hydrogen bond donor (D), hydrophobic (H), and two rings (RR). An atom-based 3D quantitative structure-activity relationship (QSAR) model showed good correlative and satisfactory predictive. The pharmacophore and 3D QSAR models can provide assistance to design novel, potential GSK-3 inhibitors with high potency and selectivity pattern, with potential application for the treatment of GSK-3-driven diseases. A class of purine nucleoside antileukemic drugs was identified as potential inhibitor of GSK-3, suggesting the reassessment of the target range of these drugs.


News Methods Funding Collaborations

Machine Vision Helps Spot New Drug Treatments

January 21st 2017, Posted by: Drug Repurposing Portal

A startup uses algorithms that understand the anatomy of cells to discover new uses for existing drugs.


News Methods Funding Collaborations

Link prediction in drug-target interactions network using similarity indices

January 21st 2017, Posted by: Drug Repurposing Portal

In silico drug-target interaction (DTI) prediction plays an integral role in drug repositioning. One popular method of drug repositioning is network-based DTI prediction, which uses complex network theory to predict DTIs from a drug-target network. DTI prediction of this algorithm makes use of only network topology information yield higher precision for high-ranking predictions than Restricted Boltzmann Machines (RBM) when no information regarding DTI types is available.


News Methods Funding Collaborations

The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication

January 18th 2017, Posted by: Drug Repurposing Portal

Zika virus (ZIKV) is a member of the Flaviviridae family, along with other agents of clinical significance such as dengue (DENV) and hepatitis C (HCV) viruses. Since ZIKV causes neurological disorders during fetal development and in adulthood, antiviral drugs are necessary. Sofosbuvir is clinically approved for use against HCV and targets the protein that is most conserved among the members of the Flaviviridae family, the viral RNA polymerase. Indeed, we found that sofosbuvir inhibits ZIKV RNA polymerase, targeting conserved amino acid residues. Sofosbuvir inhibited ZIKV replication in different cellular systems, such as hepatoma (Huh-7) cells, neuroblastoma (SH-Sy5y) cells, neural stem cells (NSC) and brain organoids. In addition to the direct inhibition of the viral RNA polymerase, we observed that sofosbuvir also induced an increase in A-to-G mutations in the viral genome. Together, our data highlight a potential secondary use of sofosbuvir, an anti-HCV drug, against ZIKV.


News Methods Funding Collaborations

Increasing Niacin Intake May Benefit Parkinson's Patients

January 14th 2017, Posted by: Drug Repurposing Portal

Recent research in fruit flies from Dr. Miguel Martins, of the University of Leicester suggests eating a niacin-rich diet could benefit people with early-onset Parkinson's disease by boosting levels of the compound NAD, which is vital for keeping mitochondria healthy. Niacin, also known as vitamin B3, is made into NAD in the body and can be found in foods such as nuts and meat. Parkinson's disease occurs when dopaminergic neurons in a part of the brain called the substantia nigra are lost, said study leader Dr. Miguel Martins, of the University of Leicester, said in a statement. This can happen for a variety of reasons, but in some hereditary cases, the main problem is unhealthy mitochondria the organelles that power the cell.


News Methods Funding Collaborations

Construction of an miRNA-regulated drug-pathway network reveals drug repurposing candidates for myasthenia gravis

January 11th 2017, Posted by: Drug Repurposing Portal

Myasthenia gravis (MG) is a rare debilitating autoimmune neuromuscular disorder. Many studies have focused on the mechanism and treatment strategies of MG. However, the exact pathogenesis of MG and effective treatment strategies remain unclear. Recent studies have indicated that microRNAs (miRNAs or miRs) can regulate the pathological pathways of MG, suggesting their potential role in novel treatments. In the present study, we created a comprehensive catalog of experimentally confirmed MG risk genes and miRNAs by manually mining published literature and public databases. Based on these genes and miRNAs, we identified 41 MG risk pathways and 105 approved drugs that can affect these pathways. Some important MG-related pathways, such as hsa04060 (cytokine-cytokine receptor interaction) and hsa05200 (pathway in cancer), were found to be regulated by MG risk miRNAs and drugs. Furthermore, we constructed an miRNA-regulated drug-pathway network and identified miRNAs and drugs that synergistically regulate key MG pathways and biological processes. We developed a drug repurposing strategy to identify 25 drug repurposing candidates for MG; several of these drugs, such as rituximab, adalimumab, sunitinib, and muromonab, have the potential to be novel MG treatment drugs. This study provides novel insight into the pathogenesis of MG and potential drug candidates for MG were identified.


News Methods Funding Collaborations

Repurposing an antidandruff agent to treating cancer: zinc pyrithione inhibits tumor growth via targeting proteasome-associated deubiquitinases

January 10th 2017, Posted by: Drug Repurposing Portal

Zhao et al report that zinc pyrithione (ZnPT) targets the proteasome-associated DUBs (USP14 and UCHL5) and inhibits their activities, resulting in a rapid accumulation of protein-ubiquitin conjugates, but without inhibiting the proteolytic activities of 20S proteasomes. Furthermore, ZnPT exhibits cytotoxic effects against various cancer cell lines in vitro, selectively kills bone marrow cells from leukemia patients ex vivo, and efficiently inhibits the growth of lung adenocarcinoma cancer cell xenografts in nude mice. The ubiquitin-proteasome system (UPS) plays a central role in various cellular processes through selectively degrading proteins involved in critical cellular functions. Targeting UPS has been validated as a novel strategy for treating human cancer, as inhibitors of the 20S proteasome catalytic activity are currently in clinical use for treatment of multiple myeloma and other cancers, and the deubiquitinase activity associated with the proteasome is also a valid target for anticancer agents. This study has identified zinc pyrithione, an FDA-approved pharmacological agent with potential antitumor properties as a proteasomal DUB inhibitor.


News Methods Funding Collaborations

New Study Shows Promise for Repurposing Anti-Malarial Drug for Cancer Treatment

January 10th 2017, Posted by: Drug Repurposing Portal

A new study by University of Kentucky Markey Cancer Center researchers shows that chloroquine, a drug currently used to treat malaria, may be useful in treating patients with metastatic cancers.


News Methods Funding Collaborations

Repurposing of Potent Drug Candidates for Multiparasite Targeting

January 9th 2017, Posted by: Drug Repurposing Portal

Parasite-directed drug discovery efforts require sustained and substantial scientific resources. Many eukaryotic parasites share similarities in metabolic pathways and housekeeping genes, as evident from their underlying protein sequences. Their subsequent structural congruence within enzyme active sites can thus be leveraged for multiparasite targeting using similar or identical drug probes. This bodes well for delivering new anti-infectives.


News Methods Funding Collaborations

Repurposing Antiestrogens for Tumor Immunotherapy

January 7th 2017, Posted by: Drug Repurposing Portal

Svoronos and colleagues observed estrogen receptor alpha-positive cells in the tumor stroma of patients with ovarian cancer that appeared to be independent of both the tumor's estrogen receptor status and tumor type. These cells were identified as immunosuppressive myeloid-derived suppressor cells (MDSC) and could be targeted by antiestrogen therapy, thereby leading to the hypothesis that endocrine therapy when combined with immunotherapy may provide a potential therapeutic benefit by helping to reduce immunosuppressive MDSCs.


News Methods Funding Collaborations

Paradigm pushes into drug repurposing

January 6th 2017, Posted by: Drug Repurposing Portal

The drug pentosan polysulfate sodium (PPS) is essentially an anti-inflammatory and an antihistamine with biological characteristics that make it ideally suited for treating hayfever and edema and viral arthritis. However, Paradigm Biopharmaceuticals is testing PPS for new indications and it has patent applications relating to the use of PPS in the treatment of Ross River virus and Chikungunya. Chief executive of Paradigm Biopharmaceuticals, Paul Rennie, said regulatory shifts would make it difficult for the large pharmaceutical companies to replicate massive profits and give smaller players an opportunity to find profits.


News Methods Funding Collaborations

DockingApp: a user friendly interface for facilitated docking simulations with AutoDock Vina

January 6th 2017, Posted by: Drug Repurposing Portal

Molecular docking is a powerful technique that helps uncover the structural and energetic bases of the interaction between macromolecules and substrates, endogenous and exogenous ligands, and inhibitors. Moreover, this technique plays a pivotal role in accelerating the screening of large libraries of compounds for drug development purposes. The need to promote community-driven drug development efforts, especially as far as neglected diseases are concerned, calls for user-friendly tools to allow non-expert users to exploit the full potential of molecular docking. Along this path, here is described the implementation of DockingApp, a freely available, extremely user-friendly, platform-independent application for performing docking simulations and virtual screening tasks using AutoDock Vina. DockingApp sports an intuitive graphical user interface which greatly facilitates both the input phase and the analysis of the results, which can be visualized in graphical form using the embedded JMol applet. The application comes with the DrugBank set of more than 1400 ready-to-dock, FDA-approved drugs, to facilitate virtual screening and drug repurposing initiatives. Furthermore, other databases of compounds such as ZINC, available also in AutoDock format, can be readily and easily plugged in.


News Methods Funding Collaborations

Repurposing Antiestrogens for Tumor Immunotherapy

January 6th 2017, Posted by: Drug Repurposing Portal

Svoronos and colleagues observed estrogen receptor alpha positive cells in the tumor stroma of patients with ovarian cancer that appeared to be independent of both the tumor's estrogen receptor status and tumor type. These cells were identified as immunosuppressive myeloid-derived suppressor cells (MDSC) and could be targeted by antiestrogen therapy, thereby leading to the hypothesis that endocrine therapy when combined with immunotherapy may provide a potential therapeutic benefit by helping to reduce immunosuppressive MDSCs.


News Methods Funding Collaborations

Metformin Exerts Antiproliferative and Anti-metastatic Effects Against Cholangiocarcinoma Cells by Targeting STAT3 and NF-κB

January 6th 2017, Posted by: Drug Repurposing Portal

This study demonstrated the antiproliferative and anti-metastatic activity of metformin, an anti-diabetic drug, in Cholangiocarcinoma (CCA) cells. Metformin significantly suppressed proliferation of CCA cells in a dose- and timedependent manner, regardless of glucose present in the medium. A low dose of metformin significantly increased anoikis and inhibited migration/ invasion of CCA cells that was in concert with the decrease of vimentin, matrix metalloproteinase (MMP)- 2 and -7. Activation of 5' adenosine monophosphate-activated protein kinase (AMPK) by phosphorylation together with suppression of nuclear translocation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor-kappa B (NF-κB) were the underlying mechanisms for these effects. Thus, Metformin is a potent antiproliferative and antimetastatic agent against human CCA cells. These findings encourage the repurposing of metformin in clinical trials to improve CCA treatment.


News Methods Funding Collaborations

Repurposing N,N'-bis-(arylamidino)-1,4-piperazinedicarboxamidines: An unexpected class of potent inhibitors of cholinesterases

January 5th 2017, Posted by: Drug Repurposing Portal

Picloxydine, an established antiseptic, was shown to be an inhibitor for acetyl- and butyrylcholinesterase. Systematic variation of the aryl substituents led to analogs possessing almost the same enzyme inhibiting properties as gold standard galantamine hydrobromide. While p-nitro substituted compound 43 (4-NO2) was a good inhibitor for AChE, p-tert-butyl substituted bisbiguanide 42(4-tButyl) inhibited BChE in the low μM range.


News Methods Funding Collaborations

Novel Therapeutics Identification for Fibrosis in Renal Allograft Using Integrative Informatics Approach

January 4th 2017, Posted by: Drug Repurposing Portal

Chronic allograft damage, defined by interstitial fibrosis and tubular atrophy (IF/TA), is a leading cause of allograft failure. Few effective therapeutic options are available to prevent the progression of IF/TA. We applied a meta-analysis approach?on IF/TA molecular datasets in Gene Expression Omnibus to identify a robust 85-gene signature, which was used for computational drug repurposing analysis. Among the top ranked compounds predicted to be therapeutic for IF/TA were azathioprine, a drug to prevent acute rejection in renal transplantation, and kaempferol and esculetin, two drugs not previously described to have efficacy for IF/TA. We experimentally validated the anti-fibrosis effects of kaempferol and esculetin using renal tubular cells in vitro and in vivo in a mouse Unilateral Ureteric Obstruction (UUO) model. Kaempferol significantly attenuated TGF-β1-mediated profibrotic pathways in vitro and in vivo, while esculetin significantly inhibited Wnt/β-catenin pathway in vitro and in vivo. Histology confirmed significantly abrogated fibrosis by kaempferol and esculetin in vivo. We developed an integrative computational framework to identify kaempferol and esculetin as putatively novel therapies for IF/TA and provided experimental evidence for their therapeutic activities in vitro and in vivo using preclinical models. The findings suggest that both drugs might serve as therapeutic options for IF/TA.


News Methods Funding Collaborations

REPRODUCIBLE DRUG REPURPOSING: WHEN SIMILARITY DOES NOT SUFFICE

January 4th 2017, Posted by: Drug Repurposing Portal

Repurposing existing drugs for new uses has attracted considerable attention over the past years. To identify potential candidates that could be repositioned for a new indication, many studies make use of chemical, target, and side effect similarity between drugs to train classifiers. Despite promising prediction accuracies of these supervised computational models, their use in practice, such as for rare diseases, is hindered by the assumption that there are already known and similar drugs for a given condition of interest. In this study, using publicly available data sets, we question the prediction accuracies of supervised approaches based on drug similarity when the drugs in the training and the test set are completely disjoint. We first build a Python platform to generate reproducible similarity-based drug repurposing models. Next, we show that, while a simple chemical, target, and side effect similarity based machine learning method can achieve good performance on the benchmark data set, the prediction performance drops sharply when the drugs in the folds of the cross validation are not overlapping and the similarity information within the training and test sets are used independently. These intriguing results suggest revisiting the assumptions underlying the validation scenarios of similarity-based methods and underline the need for unsupervised approaches to identify novel drug uses inside the unexplored pharmacological space. We make the digital notebook containing the Python code to replicate our analysis that involves the drug repurposing platform based on machine learning models and the proposed disjoint cross fold generation method freely available at github.com/emreg00/repurpose.


News Methods Funding Collaborations

Identifying New Antiepileptic Drugs Through Genomics-Based Drug?Repurposing

January 4th 2017, Posted by: Drug Repurposing Portal

Currently available antiepileptic drugs (AEDs) fail to control seizures in 30% of patients. Genomics-based drug repurposing (GBR) offers the potential of savings in the time and cost of developing new AEDs. In the current study, we used published data and software to identify the transcriptomic signature of chornic temporal lobe epilepsy and the drugs that reverse it. After filtering out compounds based on exclusion criteria, such as toxicity, 36 drugs were retained. 11 of the 36 drugs identified (>30%) have published evidence of antiepileptic efficacy (for example, curcumin) or antiepileptogenic affect (for example, atorvastatin) in recognised rodent models or patients. By objectively annotating all 20,000 compounds in the LINCS database as either having published evidence of antiepileptic efficacy or lacking such evidence, we demonstrated that our set of repurposable drugs is 6-fold more enriched with drugs having published evidence of antiepileptic efficacy in animal models than expected by chance (p-value <0.006). Further, we showed that another of our GBR-identified drugs, the commonly-used well-tolerated antihyperglycemic sitagliptin, produces a dose-dependent reduction in seizures in a mouse model of pharmacoresistant epilepsy. In conclusion, GBR successfully identifies compounds with antiepileptic efficacy in animal models and, hence, it is an appealing methodology for the discovery of potential AEDs.


News Methods Funding Collaborations

Repurposing Existing Drugs for New Indications

January 1st 2017, Posted by: Drug Repurposing Portal

In 2010, Bruce Bloom, CEO of Illinois-based Cures Within Reach, reviewed the organization?s decade-long track record of bringing new treatments to patients. He found that the non-profit had funded 190 novel drug projects, but ?couldn?t find any instance where it was directly helping patients,? says Bloom. Cures Within Reach had also funded 10 different drug repurposing projects, seeking to test existing drugs for novel indications. Of the 10 projects, four generated enough evidence to give physicians confidence to treat patients off-label, which doctors can do at their discretion, particularly when there is no approved therapy for a condition or when a patient has exhausted all available treatment options.


News Methods Funding Collaborations

Predicting High-Impact Pharmacological Targets by Integrating Transcriptome and Text-Mining Features

December 31st 2016, Posted by: Drug Repurposing Portal

Novel, "outside of the box" approaches are needed for evaluating candidate molecules, especially in oncology. Throughout the years of 2000-2010, the efficiency of drug development fell to barely acceptable levels, and in the second decade of this century, levels have improved only marginally. This dismal condition continues despite unprecedented progress in the development of a variety of high-throughput tools, computational methods, aggregated databases, drug repurposing programs and innovative chemistries. Here we tested a hypothesis that the economic impact of targeting a particular gene product is predictable a priori by employing a combination of transcriptome profiles and quantitative metrics reflecting existing literature.


News Methods Funding Collaborations

Repurposing multiple sclerosis drug dimethyl fumarate, a promising fast track candidate for systemic cutaneous T cell lymphoma treatment

December 26th 2016, Posted by: Drug Repurposing Portal

In their recent publication in?Blood, Nicolay et al. (1) report that the immune-modulatory drug dimethyl fumarate (DMF), which is approved for treatment of relapsing-remitting multiple sclerosis (MS) exerts profound effects on cutaneous T cell lymphoma (CTCL) cells from human patients?in vitro and inhibits tumor growth and distant metastasis in two different animal models of CTCL. Mechanistically, DMF restored the sensitivity of CTCL cells towards apoptosis by down-modulating elevated NF-κB activity in these cells as well as NF-κB-dependent target gene expression in tumor cells. Importantly, this restoration of apoptosis sensitivity was observed only in tumor cells but not in healthy lymphocytes, hence pointing towards a highly attractive tumor-specific mechanism with minor side effects and a well-known safety profile.


News Methods Funding Collaborations

Ancient Chinese Malaria Remedy Fights TB

December 26th 2016, Posted by: Drug Repurposing Portal

A centuries-old herbal medicine, discovered by Chinese scientists and used to effectively treat malaria, has been found to potentially aid in the treatment of tuberculosis and may slow the evolution of drug resistance. In a promising study led by Robert Abramovitch, a Michigan State University microbiologist and TB expert, found that artemisinin attacks a molecule called heme, which is found in the Mtb oxygen sensor. By disrupting this sensor and essentially turning it off, the artemisinin stopped the disease's ability to sense how much oxygen it was getting. After screening 540,000 different compounds, Abramovitch also found five other possible chemical inhibitors that target the Mtb oxygen sensor in various ways and could be effective in treatment as well.


News Methods Funding Collaborations

Certain High Blood Pressure Drugs Block Cancer Invasion

December 20th 2016, Posted by: Drug Repurposing Portal

By screening already approved drugs, the team led by Postdoctoral Researcher Guillaume Jacquemet and Academy Professor Johanna Ivaska has discovered that calcium channel blockers can efficiently stop cancer cell invasion in vitro. Calcium channel blockers are currently used to treat hypertension, also known as high blood pressure, but their potential use in blocking cancer cell metastases has not been previously reported. Myosin-10 expressing cancers have a large number of structures called filopodia. They are sticky finger-like structures the cancer cells extend to sense their environment and to navigate invasion. The team found that calcium channel blockers target specifically these sticky fingers rendering them inactive, thus efficiently blocking cancer cell movement. The team and their collaborators are currently assessing the efficiency of calcium channel blockers to stop the spreading of breast and pancreatic cancer using pre-clinical models and analysing patient data.


News Methods Funding Collaborations

Do Cancer Drugs Counteract Neurodegeneration? Repurposing for Alzheimer's Disease

December 20th 2016, Posted by: Drug Repurposing Portal

Despite in-depth investigations in the field of the amyloid cascade hypothesis, so far, Alzheimer?s disease (AD) has still not met the adequate therapy. The pathophysiology studies do provide some evidence of the inverse correlation between cancer and AD. Both AD and cancer are characterized by abnormal cellular behaviors; trigger factors along with a meta synchronously action is expected to drive cancer or neurodegeneration, supporting, respectively, progressive neuronal loss or uncontrolled cell proliferation in cancer cells. So far, cancer and AD are seemingly two opposite ends of the same biological spectrum. Basic science increasingly indicates shared molecular mechanisms between cancer and AD and gives weight to key relevant biological theories; according to them, the inverse tuning of clustered gene expression, the sharing of mutual independent pathway or the deregulated unfolded proteins system (UPR) may count for this inverse association. Additionally, the common biological background gave credibility to the recent discovery of a repurposing role for cancer drugs in AD. It refers to the development of new uses for existing pharmaceuticals having the same role as the original mechanism or to the discovery of a new drug action with disease modifying effects. The current article summarizes the most important biological theories that link neurodegeneration and cancer and provides an up-to-date revision of the repurposing cancer agents for AD. The review also addresses the gap of knowledge, since drug cancer repositioning holds an important promise but further investigations are warranted to ascertain the clinical relevance of such attractive clinical candidate compounds for AD.


News Methods Funding Collaborations

Repurposing toremifene for the treatment of oral bacterial infections

December 19th 2016, Posted by: Drug Repurposing Portal

The spread of antibiotic resistance and the challenges associated with antiseptics such as chlorhexidine have necessitated the search for new antibacterial agents against oral bacterial pathogens. As a result of failing traditional approaches, drug repurposing has emerged as a novel paradigm to find new antibacterial agents. In this study, we examined the effect of the FDA-approved anticancer agent toremifene against oral bacteria Porphyromonas gingivalis and Streptococcus mutans. We found that the drug was able to inhibit growth of both pathogens as well as prevent biofilm formation at concentrations ranging from 12.5 to 25 μM. Moreover, toremifene was shown to eradicate preformed biofilms at concentrations ranging from 25 to 50 μM. In addition, we found that toremifene prevents P. gingivalis and S. mutans biofilm formation on titanium surfaces. A time-kill study indicated that toremifene acts bactericidal against S. mutans Macromolecular synthesis assays revealed that treatment with toremifene does not cause preferential inhibition of DNA, RNA, or protein synthesis pathways, indicating membrane-damaging activity. Biophysical studies using fluorescent probes and fluorescence microscopy further confirmed the membrane-damaging mode of action. Taken together, our results suggest that the anti-cancer agent toremifene is a suitable candidate for further investigation for the development of new treatment strategies for oral bacterial infections.


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Diabetes drug slows down Parkinson's Disease

December 18th 2016, Posted by: Drug Repurposing Portal

The trial drug MSDC-0160 was developed by the Metabolic Solutions Development Company with the aim of combating diabetes. Further explorations of the drug mechanism showed that its mode of activity could extend more widely, and this led to animal trials to explore the ability of the drug to slowdown the progression of Parkinson's disease. The use of a drug, developed for one condition for a different pathology, is called drug repurposing.


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Repurposing Schizophrenia Drug for Weight Loss

December 17th 2016, Posted by: Drug Repurposing Portal

The N-methyl-d-aspartate (NMDA) receptors in the dorsal vagal complex (DVC, responsible for regulating digestive organs) are known to lower glucose production and food intake in rodents, and are activated by glycine. The glycine transporter 1 (GlyT1) acts as the main regulator of glycine levels for NMDA receptors and its inhibition results in increased extracellular glycine levels, which then activate the NMDA receptors. GlyT1 inhibitors have been previously used to help treat schizophrenia. In clinical studies, GlyT1 inhibitors have been shown to improve schizophrenic symptoms by inhibiting GlyT1, resulting in the activation of NMDA receptors by glycine.?Author here stated that GlyT1 inhibition in both type 1 and type 2 diabetes can be investigated and this can serve as viable treatment options for diabetes and weight loss.


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Certain High Blood Pressure Drugs Block Cancer Invasion

December 16th 2016, Posted by: Drug Repurposing Portal

Researchers at the University of Turku have identified a new way of blocking the spread of cancer. Calcium channel blockers, which are used to lower blood pressure, block breast and pancreatic cancer invasion by inhibiting cellular structures.


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Ocugen Closes $6 Million in Series A Funding

December 15th 2016, Posted by: Drug Repurposing Portal

Ocugen, Inc., a biopharmaceutical company developing treatments for sight-threatening diseases, today announced that it has closed a $6 million round of Series A funding to continue development efforts for its lead asset "OCU300", a repurposed drug with an established safety track record in ocular applications that is being developed for the treatment of ocular graft versus host disease (oGVHD) under the U.S. Food and Drug Agency's 505(b)(2) regulatory pathway.


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UQ study seeks Parkinson's treatment in existing drug

December 15th 2016, Posted by: Drug Repurposing Portal

Dr Richard Gordon and team at University of Queensland, School of Biomedical Sciences, are investigating the potential of repurposing an existing blood pressure drug to slow or halt the progression of Parkinson's disease. This drug has been prescribed since 1990s and the research aims to block the brain inflammation, a mechanism to stop formation of Lewy bodies.


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Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System

December 11th 2016, Posted by: Drug Repurposing Portal

The promise of drug repurposing is that existing drugs may be used for new disease indications in order to curb the high costs and time for approval. The goal of computational methods for drug repurposing is to enable solutions for safer, cheaper and faster drug discovery. Towards this end, we developed a novel method that integrates genetic and clinical phenotype data from large-scale GWAS and PheWAS studies with detailed drug information on the concept of transitive Drug-Gene-Disease triads. We created "RE:fine Drugs," a freely available, interactive dashboard that automates gene, disease and drug-based searches to identify drug repurposing candidates. This web-based tool supports a user-friendly interface that includes an array of advanced search and export options. Results can be prioritized in a variety of ways, including but not limited to, biomedical literature support, strength and statistical significance of GWAS and/or PheWAS associations, disease indications and molecular drug targets. Here we provide a protocol that illustrates the functionalities available in the "RE:fine Drugs" system and explores the different advanced options through a case study.


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Diabetes drug may be effective in treating Parkinson's

December 8th 2016, Posted by: Drug Repurposing Portal

Research shows that diabetes drug-MSDC-0160, has potential to regulate mitochondrial function in brain cells and restore the cells ability to convert basic nutrients into energy. This enhanced ability of cell to handle potentially harmful proteins results in reduced inflammation and cell death. It is reported that this drug is now ready for human trials.


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New Application of Existing Drug Offers Personalized Therapy for Lung Cancer

December 8th 2016, Posted by: Drug Repurposing Portal

A subset of lung tumours is exquisitely sensitive to a class of recently approved anti-cancer drugs. Researchers at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences in Vienna and the Ludwig Institute for Cancer Research in Oxford published this finding in the journal Nature Communications. Lung cancer remains the leading cause of cancer-related deaths worldwide. In contrast to other tumour types, lung tumours present a high number of genomic alterations. About 10% of lung tumours carry mutations in a gene called ATM. It was found ATM mutant cells fail cope with the blocking of MEK and die. MEK is part of a biochemical pathway which is responsible for supporting proliferation and survival of the cell. MEK inhibitors have so far been approved for the treatment of a type of skin cancer but not for lung cancer. Given that ATM mutant tumour is among the most prevalent for both men and women worldwide, a significant number of patients could benefit from a MEK inhibitor based treatment.


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Using Drugs for Different Diseases Than Initially Intended For

December 5th 2016, Posted by: Drug Repurposing Portal

Baumbach's team from University of Southern Denmark found approximately 30,000 "repurposable" drug candidates. Of these, about?11,000 have already been mentioned in scientific literature, and about 1,400 are reported in literature as concrete "repurposing" options.


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Calcipotriol, a topical medication of psoriasis, as a novel immunotherapeutic drug for cancer

December 5th 2016, Posted by: Drug Repurposing Portal

Actinic keratosis is a precursor of a type of skin cancer called squamous cell carcinoma. Thymic stromal lymphopoietin (TSLP) is an epithelium-derived cytokine that induces a robust antitumor immunity in barrier-defective skin. The study published in Journal of Clinical Investigation, presents that Calcipotriol, an inducer of TSLP, acts synergistically with chemotherapy drug 5-fluorouracil (5-FU) for skin cancer precursor immunotherapy.


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Drug-repositioning screens identify Triamterene as a selective "drug" for the treatment of DNA Mismatch Repair deficient cells

December 2nd 2016, Posted by: Drug Repurposing Portal

Therapies targeting the deficiencies in DNA mismatch repair pathway genes are clinically beneficial against cancers. A drug-repositioning approach employing a compound drug library of approved drugs identified Triamterene, a potassium-sparing diuretic with an ability to exhibit cytotoxicity in MMR deficient cell lines & tumors. This activity of Triamterene is attributed to its antifolate activity, leading to thymidylate synthase-dependent ROS resulting in increased DNA double strand breaks and aiding in the treatment of MMR-deficient tumors.


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A comprehensive map of molecular drug targets

December 2nd 2016, Posted by: Drug Repurposing Portal

Definition of drug target is important for the success of the mechanism-based drug discovery, when we link drug response to genetic variation, rationalize the differences between drugs in the same therapeutic class. This paper present an updated comprehensive map of molecular targets of approved drugs. A total of 893 biomolecules have been curated through which 1578 FDA approved drugs act. Further the relationship between bioactivity class and clinical success was explored, as well as the presence of orthologues between human and animal models. This approach is could also be used to understand the biological data for applications in drug repurposing.


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Repurposing Sunitinib for augmentation of Oncolytic reovirus immunotherapeutic efficacy

December 1st 2016, Posted by: Drug Repurposing Portal

The author had investigated the ability of Sunitnib, A multi-tyrosine kinase inhibitor, to augment the antitumor immune response generated by oncolytic reovirus in Renal cell cancer. The synergistic activity of Sunitinib and oncolytic reovirus was checked at both In Vitro and In Vivo system. Reovirus monotherapy reduced tumor burden and generated a systemic adaptive antitumor immune response by increasing tumor-specific CD8+?IFN?-producing cells. Co-administration of sunitinib with reovirus further reduced tumor burden resulting in improved survival, decreased accumulation of immune suppressor cells, and the establishment of protective immunity upon tumor rechallenge.


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Alzheimer's Patients may Benefit Significantly From an Array of Diabetes Treatments

December 1st 2016, Posted by: Drug Repurposing Portal

The linked underlying role of dysregulated insulin signalling in T2DM and Alzheimer's disease pathophysiology is becoming increasingly apparent, suggesting that therapeutic approaches established within T2DM could also prove to be beneficial for the treatment of Alzheimer's.


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Antiseptic used in WWI could hold key to treating superbugs, viral infections

November 28th 2016, Posted by: Drug Repurposing Portal

An antiseptic, Acriflavine used to treat wounds during World War I that has been out of use for more than 50 years could help fight superbugs (antibiotic resistant bugs) and prevent future pandemics, Melbourne researchers have said. Acriflavine basically produced a "double effect", On one hand to have an antibacterial effect, and on the other hand we discovered this capacity to instigate an immune response of the host, to protect the host. And This drug which has been used before in humans is potentially easier than making a new drug.


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Repurposing the anti-malarial drug dihydroartemisinin suppresses metastasis of non-small-cell lung cancer via inhibiting NF-?B/GLUT1 axis

November 24th 2016, Posted by: Drug Repurposing Portal

Non-small-cell lung cancer (NSCLC) is an aggressive malignancy and long-term survival remains unsatisfactory for patients with metastatic and recurrent disease. Repurposing the anti-malarial drug dihydroartemisinin (DHA) has been proved to possess potent antitumor effect on various cancers. However, the effects of DHA in preventing the invasion of NSCLC cells have not been studied. In the present study, we determined the inhibitory effects of DHA on invasion and migration and the possible mechanisms involved using A549 and H1975 cells. DHA inhibited in vitro migration and invasion of NSCLC cells even in low concentration with little cytotoxicity. Additionally, low concentration DHA also inhibited Warburg effect in NSCLC cells. Mechanically, DHA negatively regulates NF-?B signaling to inhibit the GLUT1 translocation. Blocking the NF-?B signaling largely abolishes the inhibitory effects of DHA on the translocation of GLUT1 to the plasma membrane and the Warburg effect. Furthermore, GLUT1 knockdown significantly decreased the inhibition of invasion, and migration by DHA. Our results suggested that DHA can inhibit metastasis of NSCLC by targeting glucose metabolism via inhibiting NF-?B signaling pathway and DHA may deserve further investigation in NSCLC treatment


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An Integrative Drug Repurposing Pipeline: Switching Viral Drugs to Breast Cancer

November 23rd 2016, Posted by: Drug Repurposing Portal

Resistance due to mutation is more common in Breast Cancer and there are no feasible tactics to overcome this bottleneck. A multi-modal computational drug repositioning approach proposed by scientists at VIT University suggest that Ombitasvir, a Hepatitis C NS5B Polymerase inhibitor, could be "repurposed" for the control and prevention of beta-tubulin driven breast cancers.


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Cancer drug, Sunitinib, may boost muscle strength for patients of FSHD

November 23rd 2016, Posted by: Drug Repurposing Portal

A study reveals that a drug used to treat kidney and stomach cancers could be effectively repurposed for reducing muscle weakness and wasting in patients with a form of muscular dystrophy. Dr. Robert Knight and his colleagues, recently published in the journal eLife, suggest the cancer drug sunitinib may improve muscle weakness in patients with facioscapulohumeral dystrophy (FSHD). FSHD is caused by the shortening of D4Z4 regions of DNA on chromosome 4. At present, there are no medications that can improve muscle strength in patients with FSHD. Sunitinib is a medication for the treatment of renal cell carcinoma. The drug works by blocking receptor tyrosine kinase (RTK), which is a type of chemical messenger that instructs cancer cells to grow. In their study, Dr. Knight and team note that a type of RTK - rearranged during transfection (RET) - is up regulated in muscle-forming stem cells, or myoblasts, that express a protein called DUX4. This protein is encoded by the DUX4 gene, situated in the D4Z4 region involved in FSHD.


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Treatments For One Type Of Dementia May Also Work In Others

November 23rd 2016, Posted by: Drug Repurposing Portal

Research has shown that many forms of dementia and neurodegenerative diseases such as ALS and Huntington's share some of the same underlying causes as Alzheimer's disease. Drugs targeting any one of these neurodegenerative diseases, could potentially treat a wide range of brain diseases and disorders, as according to the pioneer researchers in this field. So treatments for one type of brain disease could potentially be effective at treating others.


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Drug Repurposing Patent Applications

November 23rd 2016, Posted by: Drug Repurposing Portal

One of the blogs from H.M. Pharma Consultancy, provides a snapshot on the upcoming patents that were filed (PCT applications) in Q2 & Q3 2016. Few examples include beta blockers, BTK & Kinase inhibitors for applications in new disease indications. The details will be published in the upcoming issue of ASSAY and Drug Development Technologies


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Muscular dystrophy: Cancer drug may boost muscle strength for some patients

November 22nd 2016, Posted by: Drug Repurposing Portal

A study conducted by Dr. Robert Knight - of the Craniofacial Development and Stem Cell Biology Division at King's College London's Dental Institute in the United Kingdom - and colleagues reveals that a drug used to treat kidney and stomach cancers could be effective for reducing muscle weakness and wasting in patients with a form of muscular dystrophy, facioscapulohumeral dystrophy (FSHD). Sunitinib is a medication approved by the U.S. Food and Drug Administration (FDA) for the treatment of renal cell carcinoma - a form of kidney cancer - and gastrointestinal stromal tumors (GISTs), tumors of the stomach, intestine, or bowel. In their study, Dr. Knight and team note that a type of RTK - rearranged during transfection (RET) - is upregulated in muscle-forming stem cells, or myoblasts, that express a protein called DUX4. This protein is encoded by the DUX4 gene, situated in the D4Z4 region involved in FSHD. The researchers found that the cancer drug suppressed RET activity in both rodent and human myoblasts, reducing DUX4 expression and decreasing muscle cell damage. Since the drug is already approved for the treatment of cancer, its safety has already been established, meaning approval for sunitinib as a treatment for FSHD may be well within sight.


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A review of validation strategies for computational drug repositioning

November 22nd 2016, Posted by: Drug Repurposing Portal

Repositioning of previously approved drugs is a promising methodology because it reduces the cost and duration of the drug development pipeline and reduces the likelihood of unforeseen adverse events. Computational repositioning is especially appealing because of the ability to rapidly screen candidates in silico and to reduce the number of possible repositioning candidates. What is unclear, however, is how useful such methods are in producing clinically efficacious repositioning hypotheses. Furthermore, there is no agreement in the field over the proper way to perform validation of in silico predictions, and in fact no systematic review of repositioning validation methodologies. To address this unmet need, we review the computational repositioning literature and capture studies in which authors claimed to have validated their work. Our analysis reveals widespread variation in the types of strategies, predictions made and databases used as 'gold standards'. We highlight a key weakness of the most commonly used strategy and propose a path forward for the consistent analytic validation of repositioning techniques.


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Antibiotic Could Help Treat Alcohol Use Disorder

November 21st 2016, Posted by: Drug Repurposing Portal

Minocycline, a tetracycline antibiotic (Already approved by US FDA) normally used against bacterial infections, has known anti-inflammatory actions and recently was shown to reduce alcohol consumption Identified through collaborative effort between Texas Tech University Health Sciences Center (TTUHSC) researchers Oregon Health and Science University. Minocycline analog, was highly effective in reducing binge and chronic consumption, in both dependent and non-dependent animals. In addition, withdrawal seizures, which represent a medical emergency in humans, also were reduced in mice by tigecycline.


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Study Finds Arthritis Drug Significantly Effective in Treating Crohn's Disease

November 21st 2016, Posted by: Drug Repurposing Portal

Researchers at University of California San Diego School of Medicine have shown that ustekinumab, a human antibody used to treat arthritis, significantly reduced the severity of Crohn's disease. The study indicates that ustekinumab may have a long duration of action, and has not been associated with an increased risk of serious adverse events.


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In silico and in vitro drug screening identifies new therapeutic approaches for Ewing sarcoma

November 16th 2016, Posted by: Drug Repurposing Portal

The long-term overall survival of Ewing sarcoma (EWS) patients remains poor; less than 30% of patients with metastatic or recurrent disease survive despite aggressive combinations of chemotherapy, radiation and surgery. To identify new therapeutic options, we employed a multi-pronged approach using in silico predictions of drug activity via an integrated bioinformatics approach in parallel with an in vitro screen of FDA-approved drugs. Twenty-seven drugs and forty-six drugs were identified, respectively, to have anti-proliferative effects for EWS, including several classes of drugs in both screening approaches. Among these drugs, 30 were extensively validated as mono-therapeutic agents and 9 in 14 various combinations in vitro. Two drugs, auranofin, a thioredoxin reductase inhibitor, and ganetespib, an HSP90 inhibitor, were predicted to have anti-cancer activities in silico and were confirmed active across a panel of genetically diverse EWS cells. When given in combination, the survival rate in vivo was superior compared to auranofin or ganetespib alone. Importantly, extensive formulations, dose tolerance, and pharmacokinetics studies demonstrated that auranofin requires alternative delivery routes to achieve therapeutically effective levels of the gold compound. These combined screening approaches provide a rapid means to identify new treatment options for patients with a rare and often-fatal disease.


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Computational Drug Target Screening through Protein Interaction Profiles

November 15th 2016, Posted by: Drug Repurposing Portal

The development of computational methods to discover novel drug-target interactions on a large scale is of great interest. We propose a new method for virtual screening based on protein interaction profile similarity to discover new targets for molecules, including existing drugs. We calculated Target Interaction Profile Fingerprints (TIPFs) based on ChEMBL database to evaluate drug similarity and generated new putative compound-target candidates from the non-intersecting targets in each pair of compounds. A set of drugs was further studied in monoamine oxidase B (MAO-B) and cyclooxygenase-1 (COX-1) enzyme through molecular docking and experimental assays. The drug ethoxzolamide and the natural compound piperlongumine, present in Piper longum L, showed hMAO-B activity with IC50 values of 25 and 65??M respectively. Five candidates, including lapatinib, SB-202190, RO-316233, GW786460X and indirubin-3'-monoxime were tested against human COX-1. Compounds SB-202190 and RO-316233 showed a IC50 in hCOX-1 of 24 and 25??M respectively (similar range as potent inhibitors such as diclofenac and indomethacin in the same experimental conditions). Lapatinib and indirubin-3'-monoxime showed moderate hCOX-1 activity (19.5% and 28% of enzyme inhibition at 25??M respectively). Our modeling constitutes a multi-target predictor for large scale virtual screening with potential in lead discovery, repositioning and drug safety.


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Redeploying β-Lactams Against Staphylococcus aureus: Repurposing With a Purpose

November 14th 2016, Posted by: Drug Repurposing Portal

β-Lactam antibiotics have been a mainstay of clinical therapeutics for approximately 70 years, especially for methicillin-susceptible Staphylococcus aureus (MSSA) infections. Since approximately one half of S. aureus bacteremias are caused by MSSA, the antistaphylococcal β-lactams remain key elements of therapeutic strategies for such infections. Data from a number of clinical trials have documented the therapeutic superiority of antistaphylococcal β-lactams over vancomycin for MSSA bacteremic infections, including endocarditis. Further, the American Heart Association has consistently recommended β-lactams as the treatment of choice for MSSA endocarditis.


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Repurposed Drug May Offer Diagnosis, Treatment for Traumatic Nerve Damage New Application of Existing Drug Offers Personalized Therapy for Lung Cancer

November 14th 2016, Posted by: Drug Repurposing Portal

Elfar et al at the University of Rochester Medical Center have been able to show that a drug previously approved for other purposes can ?wake up? damaged peripheral nerves and speed repair and functional recovery after injury. 4-aminopyridine (4AP), a drug currently used to treat patients with the chronic nerve disease, multiple sclerosis, has the unexpected property of promoting recovery from acute nerve damage.


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Antimalarial being tested as possible Ebola virus drug

November 10th 2016, Posted by: Drug Repurposing Portal

A team of researchers from the Texas biomedical research institute used bayesian machine learning models based on the earlier published dataset to screen a library of more than 2000 drugs and drug-like molecules. Subsequently, they identified 3 compounds having significant activity in vitro against the Ebola virus, which are relatively new antimalarial called pyronaridine and approved in Europe.


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Drug-Target Interactions: Prediction Methods and Applications

November 7th 2016, Posted by: Drug Repurposing Portal

Identifying the interactions between drugs and target proteins is a key step in drug discovery. This not only aids to understand the disease mechanism, but also helps to identify unexpected therapeutic activity or adverse side effects of drugs. Hence, drug-target interaction prediction becomes an essential tool in the field of drug repurposing. The availability of heterogeneous biological data on known drug-target interactions enabled many researchers to develop various computational methods to decipher unknown drug-target interactions. This review provides an overview on these computational methods for predicting drug-target interactions along with available web servers and databases for drug-target interactions. Further, the applicability of drug-target interactions in various diseases for identifying lead compounds has been outlined.


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DPDR-CPI, a server that predicts Drug Positioning and Drug Repositioning via Chemical-Protein Interactome

November 2nd 2016, Posted by: Drug Repurposing Portal

The cost of developing a new drug has increased sharply over the past years. To ensure a reasonable return-on-investment, it is useful for drug discovery researchers in both industry and academia to identify all the possible indications for early pipeline molecules. For the first time, we propose the term computational "drug candidate positioning" or "drug positioning", to describe the above process. It is distinct from drug repositioning, which identifies new uses for existing drugs and maximizes their value. Since many therapeutic effects are mediated by unexpected drug-protein interactions, it is reasonable to analyse the chemical-protein interactome (CPI) profiles to predict indications. Here we introduce the server DPDR-CPI, which can make real-time predictions based only on the structure of the small molecule. When a user submits a molecule, the server will dock it across 611 human proteins, generating a CPI profile of features that can be used for predictions. It can suggest the likelihood of relevance of the input molecule towards ~1,000 human diseases with top predictions listed. DPDR-CPI achieved an overall AUROC of 0.78 during 10-fold cross-validations and AUROC of 0.76 for the independent validation.


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Clinically Approved Ion Channel Inhibitors Close Gates for Hepatitis C Virus and Open Doors for Drug Repurposing in Infectious Viral Diseases

November 2nd 2016, Posted by: Drug Repurposing Portal

Chronic hepatitis C virus (HCV) infection causes severe liver disease and affects nearly 146 million individuals. Novel antivirals which directly target HCV have revolutionized treatment. However, high costs restricts frequent access to therapy. Recently, several related drugs used in humans to treat allergies or as neuroleptics have emerged as potent HCV cell entry inhibitors. Insights into their antiviral modes of action may increase opportunities for drug repurposing in hepatitis C and possibly other important human viral infections.


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IBM, Teva to Use A.I. for Drug Repurposing Program

October 26th 2016, Posted by: Drug Repurposing Portal

IBM's artificial intelligence program Watson is diving deeper into health care. The computing giant and Teva Pharmaceuticals announced on Wednesday that they were taking their ongoing health partnership into new territory. Both firms will work together on a chronic disease management system combining IBM's cognitive computing capabilities with Teva's therapeutic technology. This program would harness 6 billion data points along with cloud-connected drug delivery and app technology to help calculate the risk of potential health events like an asthma attack.


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A Computational Systems Biology Approach for Identifying Candidate Drugs for Repositioning for Cardiovascular Disease

October 24th 2016, Posted by: Drug Repurposing Portal

Combining disease-associated gene sets,drug-transcriptome-responses datasets and drug-target annotations can potentially be useful as a screening tool for diseases that lack an accepted cellular model for in vitro screening. With this view, a dataset of transcriptome responses of a cell line to a panel of drugs; two sets of genes for the disease; and mappings between drugs and the receptors or pathways that they target, were integrated. The application of this method to data from (1) CMap 2.0; (2) gene sets from two transcriptome profiling studies of atherosclerosis; and (3) a combined dataset of drug/target information recapitulated the known targets related to CVD (e.g., PPARγ ; HMG-CoA reductase, HDACs) and novel targets (e.g., amine oxidase A, σ-opioid receptor). From this study it can be concluded that this method can potentially be useful as a screening tool for diseases that lack an accepted cellular model for in vitro screening.


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Drug repurposing by integrated literature mining and drug-gene-disease triangulation

October 22nd 2016, Posted by: Drug Repurposing Portal

Drug design is expensive, time-consuming and becoming increasingly complicated. Computational approaches for inferring potentially new purposes of existing drugs, referred to as drug repositioning, play an increasingly important part in current pharmaceutical studies. Here, we first summarize recent developments in computational drug repositioning and introduce the utilized data sources. Afterwards, we introduce a new data fusion model based on n-cluster editing as a novel multi-source triangulation strategy, which was further combined with semantic literature mining. Our evaluation suggests that utilizing drug-gene-disease triangulation coupled to sophisticated text analysis is a robust approach for identifying new drug candidates for repurposing.


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Drug Repositioning in Inflammatory Bowel Disease Based on Genetic Information

October 21st 2016, Posted by: Drug Repurposing Portal

We hypothesized that proteins encoded by IBD candidate genes are potential IBD drug targets because genetic information can increase successful drug identification. We identified drugs that target the proteins encoded by IBD candidate genes using the DrugBank. We have identified 113 drugs that could potentially be used in IBD treatment. Fourteen are known IBD drugs, 48 drugs have been, or are being investigated in IBD, 19 are being used or being investigated in other inflammatory disorders treatment and 32 are investigational new drugs that have not yet been registered for clinical use.


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Studies suggest Inflammatory Cytokines are Associated with Depression and Psychosis, and that anti-Cytokine Treatment can Reduce Depression Symptoms

October 20th 2016, Posted by: Drug Repurposing Portal

The studies conducted by Dr Golam Khandaker, Department of Psychiatry, University of Cambridge, UK, and colleagues showed that anti-cytokine treatment can reduce depression symptoms and suggest that increased levels of inflammatory cytokines are associated with increased rates of depression and psychosis, and that treatment to reduce cytokine levels can reduce symptoms of depression. A systematic review and meta-analysis of antidepressant activity of anti-cytokine treatment (monoclonal antibodies and cytokine inhibitors) using clinical trials of chronic inflammatory conditions such as rheumatoid arthritis in which depressive symptoms were measured as a secondary outcome. Data from seven randomised controlled trials (2370 participants) showed significant antidepressant effect of anti-cytokine treatment compared with placebo.


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Identification of Potential Therapeutics to Conquer Drug Resistance in Salmonella typhimurium: Drug Repurposing Strategy

October 19th 2016, Posted by: Drug Repurposing Portal

The objective of this study was to use computational drug repurposing to identify a novel candidate with an effective mechanism of action to circumvent the drug resistance.


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Flufenamic Acid, a Cold Medicine could stop cancer Spread

October 17th 2016, Posted by: Drug Repurposing Portal

AKR1C1, Aldo-Keto Reductase family 1 member C1, catalyze the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors. Flufenamic acid, an inhibitory factor for AKR1C1, is a nonsteroid anti-inflammatory drug used for treating common colds. Dr. Shinya Tanaka at Hokkaido University discovered that Flufenamic acid decreased the cisplatin-resistance and invasion potential of metastatic bladder cancers.


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Lupus Research Alliance Launches Clinical Trial Network

October 17th 2016, Posted by: Drug Repurposing Portal

The Lupus Research Alliance launched a bold initiative, the Lupus Clinical Investigators Network (LuCIN) to accelerate the identification and development of new therapies to treat lupus. Recently LuCIN identified a bunch of FDA approved drugs through Repurposing, used for other indications, which can be used for the treatment of Lupus. The first planned LuCIN clinical trial will test RAYOS - a low-dose, delayed-release form of the steroid prednisone, an anti-inflammatory drug. RAYOS is broadly prescribed for Rheumatoid Arthritis and other common inflammatory conditions. The study will look at the effect of RAYOS on the severe fatigue often experienced by people with lupus.


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It's Time to Consider Propranolol as Anti-Cancer Drug

October 17th 2016, Posted by: Drug Repurposing Portal

Propranolol, a beta-blocker commonly prescribed to treat irregular heart rates and other conditions, has significant anti-cancer properties, say researchers in a new clinical study published in ecancer medical science. The Repurposing Drugs in Oncology (ReDO) project, an international collaboration between the Anticancer Fund, Belgium, and US based Global Cures, says that existing and widely-used non-cancer drugs may represent a relatively untapped source of novel therapies for cancer.


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Repurposing Drugs in Oncology (ReDO) Propranolol as an anti-cancer agent

October 12th 2016, Posted by: Drug Repurposing Portal

Propranolol (PRO) is a well-known and widely used non-selective beta-adrenergic receptor antagonist (beta-blocker), with a range of actions which are of interest in an oncological context. PRO displays effects on cellular proliferation and invasion, on the immune system, on the angiogenic cascade, and on tumour cell sensitivity to existing treatments. Both pre-clinical and clinical evidence of these effects, in multiple cancer types, is assessed and summarised and relevant mechanisms of action outlined. In particular there is evidence that PRO is effective at multiple points in the metastatic cascade, particularly in the context of the post-surgical wound response. Based on this evidence the case is made for further clinical investigation of the anticancer effects of PRO, particularly in combination with other agents. A number of trials are on-going, in different treatment settings for various cancers.


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