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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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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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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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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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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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.


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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.


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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.


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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.


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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.


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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.


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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.


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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


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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.


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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.


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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.


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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.


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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.


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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.


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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.


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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.


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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.


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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.


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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.


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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.


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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.


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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.


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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.


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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.


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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.


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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.


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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.


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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.


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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.


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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.


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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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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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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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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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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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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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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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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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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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Repurposing Treatments to Enhance Innate Immunity. Can Statins Improve Neutrophil Functions and Clinical Outcomes in COPD?

October 11th 2016, Posted by: Drug Repurposing Portal

Statins drug is used to help reduce cardiovascular risk, which is high in many patients with Chronic Obstructive Pulmonary Disease (COPD). Still, the mechanisms of these effects are not well studied and use of Statins are associated with improvements in some respiratory manifestations of disease. Neutrophils are key effector cells in COPD, and are correlated with disease severity and inflammation. It is shown that neutrophil functions are dysregulated in COPD and this is thought to contribute to the destruction of lung parenchyma. Here, the potential utility of statins in COPD, with a particular emphasis on their immune-modulatory effects as well as presenting new data regarding the effects of statins on neutrophil function in vitro has been discussed.


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Anti-Inflammatory Drugs for Symptoms of Depression

October 10th 2016, Posted by: Drug Repurposing Portal

Lack of Serotonin is not the only reason for depression and SSRIs (drug to increase serotonin levels) do not work for everyone. Recent research has found that around a third of people with depression appear to have higher levels of cytokines in their brains, while people with "overactive" immune systems seem more likely to develop depression. Dr. Khandaker's team found that in trials involved over 5,000 volunteers, anti-cytokine drugs can improve the symptoms of depression. Thus anti-inflammatory drugs may be used for symptoms of depression.


News Methods Funding Collaborations

Artemisinin and Its Derivatives as a Repurposing Anticancer Agent: What Else Do We Need to Do?

October 7th 2016, Posted by: Drug Repurposing Portal

The last two decades have involved the preclinical as well as investigational study of Artemisinin and its derivatives (ARTs) for their potential anticancer properties. Observations such as toxic-free radicals generated by an endoperoxide moiety, cell cycle arrest, induction of apoptosis and inhibition of tumor angiogenesis are inherent characteristics of ARTs and supposed to be the major mechanism of action. Because of which, ARTs are expected to be a new class of antitumor drugs of wide spectrum due to their well-studied efficacy and safety. For making ARTs qualify for the category of repurposed drugs, thorough investigations needs to be performed it terms of new pathways of anticancer effects, exploration on efficient and specific drug delivery systems-especially crossing biological barriers, and obtaining sufficient data in the clinical trials. This review, thus, highlights these studies and proposes the potential strategies to develop ARTs as a new class of anticancer agents.


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The Trials and Tribulations of Repurposing Metformin and other Generic Drugs for Tuberculosis

October 1st 2016, Posted by: Drug Repurposing Portal

There are a number of generic drugs that might be useful in treating tuberculosis, but will they ever get to the patients who need them. They might, but not without a lot of help. There are intellectual property issues, endpoint issues, cost of research issues, economic incentive issues, preclinical validation issues, 'who is in charge' issues and many more. It is clear that repurposed generic drugs have the potential to make a safe, effective, quick and affordable impact on a global disease of poverty such as tuberculosis. But without the economic incentives that are usually in place for drug development, can we muster the scientific, economic and governmental support to bring them to the patients.


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Kidney Cancer Drug also Attacks other Cancers

September 30th 2016, Posted by: Drug Repurposing Portal

From researching the chemical effects of hundreds of drugs on cell signaling pathways, a team of researchers at the University of Bergen in Norway has discovered that axitinib - a drug approved for the treatment of kidney cancer - can also attack other types of cancer via a different route.


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Repurposing of Anticancer Drugs for the Treatment of Bacterial Infections

September 30th 2016, Posted by: Drug Repurposing Portal

Bacterial infections are one of the leading causes of death worldwide and mortality rates are increasing at alarming rates but no new antibiotics have been produced by the pharmaceutical industry in more than a decade. Usage of anticancer molecules proven effective in vitro for eliminating recalcitrant, multidrug tolerant bacteria, some of which also protect animals from infections and recently are undergoing clinical trials. Soo et al., highlighted the similarities between cancer cells/tumors and bacterial infections, and presented evidence that supports the utilization of some anticancer drugs, including 5-fluorouracil (5-FU), gallium (Ga) compounds, and mitomycin C, as antibacterials. Each of these drugs has some promising properties such as broad activity (all three compounds), dual antibiotic and antivirulence properties (5-FU), efficacy against multidrug resistant strains (Ga), and the ability to kill metabolically dormant persister cells which cause chronic infections (mitomycin C).


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Aggregated Compound Biological Signatures facilitate Phenotypic Drug Discovery and Target Elucidation

September 26th 2016, Posted by: Drug Repurposing Portal

Predicting the cellular response of compounds is a challenge central for the discovery of new drugs. In this work, the researchers statistically aggregated signal from several biological signatures to find compounds that produce a desired phenotype in the cell. Their target-independent cellular and biochemical assay results showed (i) novel nanomolar inhibitors of cellular division that reproduce the phenotype and the mode of action of reference natural products and (ii) blockers of the NKCC1 co-transporter for autism spectrum disorders. Their target identification studies predicted new activities for drugs nimedipine, fluspirilene and pimozide that provide a rationale for repurposing and side effects.


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Comprehensive Modeling and Discovery of Mebendazole as a Novel TRAF2- and NCK-interacting Kinase Inhibitor

September 21st 2016, Posted by: Drug Repurposing Portal

TRAF2- and NCK-interacting kinase (TNIK) represents one of the crucial targets for Wnt-activated colorectal cancer. In this study, author curated two datasets and conducted a comprehensive modeling study to explore novel TNIK inhibitors with desirable biopharmaceutical properties. The obtained models were employed to screen 1,448 FDA-approved small molecule drugs. Upon experimental evaluations, author discovered that mebendazole, an approved anthelmintic drug, could selectively inhibit TNIK kinase activity with a dissociation constant Kd = ~1microM. This study represents a unique ligand-based framework for drug repurposing against a specific protein target critical for colorectal cancer treatment.


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Repurposing Escherichia coli antiadhesives in Crohn's disease

September 21st 2016, Posted by: Drug Repurposing Portal

The development of multidrug resistant bacterial strains is a global health problem requiring complementary anti-infective approaches. Among them, the anti-adhesive strategy consisting of preventing or blocking the adhesion of a toxin, virus or bacteria to the host cells is particularly promising.


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Repurposing of Approved Cardiovascular Drugs

September 20th 2016, Posted by: Drug Repurposing Portal

In this review, Ishida J., et al, detailed drug repurposing of approved cardiovascular drugs, such as aspirin, beta-blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, cardiac glycosides and statins. Repurposing of cardiovascular drugs is expanding as in other pathological conditions like cancer. The future perspective of experimental and clinical studies using repurposed cardiovascular drugs is discussed in this article.


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Repurposing N,N'-bis-(arylamidino)-1,4-piperazinedicarboxamidines: An Unexpected Class of Potent inhibitors of Cholinesterases

September 19th 2016, Posted by: Drug Repurposing Portal

Following drug repurposing, a small library of compounds was screened for their ability to act as inhibitors of acetyl- and butyrylcholinesterase. Picloxydine, an established antiseptic, was shown to be an inhibitor for both enzymes. Systematic variation of the aryl substituents led to analogs possessing almost the same good properties as gold standard galantamine hydrobromide.


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Lithium Pharmacogenetics: Where Do We Stand?

September 16th 2016, Posted by: Drug Repurposing Portal

Lithium is considered the first-line treatment for Bipolar disorder, although a large percentage of patients do not respond sufficiently. Lithium can induce severe side effects and the genetics of lithium response is poorly understood. In the current study, using drug repurposing approach, the researchers identified ebselen, as potential lithium mimetic, as it shares with lithium the ability to inhibit inositol monophosphatase. Ebselen, an antioxidant glutathione peroxidase mimetic, represents a valid and promising example of new potential therapeutic interventions for Bipolar disorder. However, the paucity of data needs further investigation to elucidate its potential efficacy and safety in the management of Bipolar disorder.


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Existing Drug may Halt Tumour Growth in Breast Cancer

September 12th 2016, Posted by: Drug Repurposing Portal

An international team including Rice University researchers suggested that pioglitazone, typically used to treat type 2 diabetes, down-regulates levels of NAF-1, which has been over-expressed in cancers such as breast, prostate, gastric, cervical, liver and laryngeal cancer. This study has been published in the Proceedings of the National Academy of Sciences.


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Abelson Kinase Inhibitors Are Potent Inhibitors of Severe Acute Respiratory Syndrome Coronavirus and Middle East Respiratory Syndrome Coronavirus Fusion

September 12th 2016, Posted by: Drug Repurposing Portal

We previously screened a library of FDA-approved drugs for inhibitors of coronavirus replication in which we identified Abelson (Abl) kinase inhibitors, including the anticancer drug imatinib, as inhibitors of both SARS-CoV and MERS-CoV in vitro. We specifically identified the imatinib target, Abelson tyrosine-protein kinase 2 (Abl2), as required for efficient SARS-CoV and MERS-CoV replication in vitro.


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Repositioning of Bromocriptine for Treatment of Acute Myeloid Leukemia (AML)

September 7th 2016, Posted by: Drug Repurposing Portal

An in silico screening was designed to search for FDA-approved small molecules that potentially induce differentiation of Acute Myeloid Leukemia (AML) cells. Bromocriptine was identified and validated in an in vitro screening. Bromocriptine is an approved drug originally indicated for Parkinson's disease, acromegaly, hyperprolactinemia and galactorrhoea, and recently repositioned for diabetes mellitus. Treatment with Bromocriptine reduced cell viability of AML cells by activation of the apoptosis program and induction of myeloid differentiation and hence Bromocriptine can be repurposed for treating AML.


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Clustering Drug-Drug Interaction Networks with Energy Model Layouts: Community Analysis and Drug Repurposing

September 7th 2016, Posted by: Drug Repurposing Portal

In this article, Udrescu L., et al developed a new approach to analyse drug-drug interaction networks, based on clustering and topological community detection techniques that are specific to complex network science. Their methodology uncovers functional drug categories along with the intricate relationships between them. The researchers linked the network clusters to 9 relevant pharmacological properties using modularity-based and energy-model layout community detection algorithms and the predicted properties were confirmed for 85% of the drugs. The authors propose that methodology can lead to drug repositioning for the 15% drugs along with other applications such as analysing drug-target interactions, phenotyping patients in personalized medicine applications.


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Old Drug Discovered as New Treatment for Ross River Fever

September 7th 2016, Posted by: Drug Repurposing Portal

A drug which has been on the market for almost five decades and is currently used to treat cystitis is being hailed the new hero in the treatment of Ross River Fever. Scientists at Griffith University's Institute for Glycomics on the Gold Coast have discovered pentosan plysulfate sodium, or PPS, provides "radical improvement" in the joint pain and inflammation associated with acute attacks of the disease which is carried and transmitted by mosquitoes.


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Ontario Scientist Thinks Old Drugs could become our New Antibiotics

September 7th 2016, Posted by: Drug Repurposing Portal

McMaster University scientist Eric Brown and his team screened thousands of chemicals that are already used to treat other diseases to see if any will work against bacteria and found that antidiarrheal medication Imodium and anticonvulsant drug lamotrigine also seem to kill bacteria. The advantage of repurposing old drugs to fight bacteria is already been tested and proven to be safe.


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Protein kinase C-δ Inhibitor, Rottlerin Inhibits Growth and Survival of Mycobacteria Exclusively through Shikimate Kinase

September 6th 2016, Posted by: Drug Repurposing Portal

Drug repurposing is one of such strategies which is being used in recent times to identify new pharmacophores. The essential first step in discovery of the specific inhibitor with low toxicity is the identification and elucidation of pathways exclusive to target pathogen. One such target is the shikimate pathway, which is essential for algae, higher plants, bacteria and fungi. Since, this enzyme system is absent in higher eukaryotes and in mammals, the enzymes involved in the pathway provide an attractive target for the development of potentially selective and non-toxic antimicrobial agents. Since, so far there is no specific inhibitor which is able to restrain mycobacterial shikimate pathway; we expanded the use of a known kinase inhibitor; Rottlerin, in order to predict the prototype in discovering the specific molecules against this enzyme. For the first time we have shown that Rottlerin inhibits extracellular mycobacteria by affecting Shikimate Kinase (SK) and this effect is further enhanced during the intracellular infection due to the added effect of PKC-δ down-regulation.


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Repurposing Drugs for Cognition in Schizophrenia

September 5th 2016, Posted by: Drug Repurposing Portal

Yang et al., has put considerable effort to repurpose drugs for schizophrenia that can improve cognition by targeting receptor systems other than the dopaminergic system.


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Repositioning of Endonuclear Receptors Binders as Potential Antibacterial and Antifungal Agents. Eptyloxm: A Potential and Novel Gyrase B and Cytochrome Cyp51 Inhibitor

September 1st 2016, Posted by: Drug Repurposing Portal

A novel class of antibacterial and antifungal agents is here identified by means of dockings and virtual screening techniques. Biological data proved the initial effort, formulated on the structure similarity of nuclear receptors binders with known quinolones or thiazole derivatives, to reposition PPARs agonists as likely bacterial type II topoisomerases inhibitors.


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Lipid Genomics searches for Therapeutic Cure to Genetic Heart Defect

August 29th 2016, Posted by: Drug Repurposing Portal

Lipid Genomics is one of 38 companies already in or coming to UConn's incubator program, which includes UConn sites in Farmington, Storrs and Avery Point. Rodriguez, a physician-scientist at UConn Health, driven to repurpose a drug to find therapeutic cure for people with good levels of the healthy HDL cholesterol but who are still at risk for heart disease and heart attacks by using probucol, that was used in the U.S. from 1977 to 1995, then licensed in Japan, where it's used to treat the bad cholesterol, LDL, but not for heart disease and heart attack.The drug received an Investigational New Drug approval from the Food and Drug Administration in 2013, but Lipid Genomics needs funding to proceed with Phase 1 trials in humans in the U.S.


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Repurposing DRD2 Antagonists for Pancreatic Cancer

August 28th 2016, Posted by: Drug Repurposing Portal

In a recent study at Canada the gene expression profile analysis of PDAC samples were studies which showed that the DRD2 signaling pathway to be activated in pancreatic cancer patients. Further the results of the study in mice models indicate that the Inhibition of DRD2 in pancreatic cancer cells reduces the proliferation and migration, and slows the growth of xenograft tumors in mice. This suggests that DRD2 antagonists routinely used for management of schizophrenia might be tested in patients with pancreatic cancer.


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Discovery of a Carbazole-Derived Lead Drug for Human African Trypanosomiasis

August 26th 2016, Posted by: Drug Repurposing Portal

The study showed that one of the carbazole compound is orally bioavailable lead for anti-trypanosome drug discovery, and established its mode of action: it blocks mitosis but allows licensing of chromosomal and kinetoplast DNA replication. Carbazoles such as carprofen and other carbazole derivatives are being evaluated as leads for drugs to treat human neurodegenerative disorder. Additionally, some carbazole derivatives are active against other protozoan parasites, such as Leishmania donovani, and Plasmodium falciparum. Thus, carbazoles are a promising chemical scaffold for ?repurposing? in an effort to discover new and better anti-trypanosomal drugs.


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2 therapies intended for other diseases may work to treat PH

August 25th 2016, Posted by: Drug Repurposing Portal

Team of researchers led by Dr. Stephen Y.Chan, from UPMC Center for Pulmonary Vascular Biology and Medicine identified two compounds Verteporfin; FDA approved drug for treating macular degeneration and CB-839; currently under clinical trials against cancer which could be useful in the treatment of Pulmonary Hypertension. These two compounds target the signaling molecules; YAP and TAZ along with their downstream target GLS1 which plays a role in energy production and energy usage in lung vessels.


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sNebula, a Network-Based Algorithm to Predict Binding between Human Leukocyte Antigens and Peptides

August 25th 2016, Posted by: Drug Repurposing Portal

Heng Luo et al., developed a network-based algorithm called sNebula that predicts HLA-peptide binding. They have used curated Class I HLA-peptide binding data to validate the algorithm and further proved the effectiveness of sNebula on those HLAs and peptides that have no existing binding data. Among other applications, this similarity based algorithm has potential to predict drug-disease association for drug repurposing.


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Major breakthrough identifies cause and treatment of fatal autoimmune disease

August 24th 2016, Posted by: Drug Repurposing Portal

The TNF blocking antibody drug, called Infliximab or Remicade, is already approved for the treatment of other autoimmune and inflammatory diseases, including rheumatoid arthritis and Crohn's disease, making its way for the treatment of OTULIN-related autoinflammatory syndrome (ORAS),It is a good example of repurposing of already clinically approved drugs.


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IntelGenx reports clinical progress on delivery of Alzheimer's drug

August 23rd 2016, Posted by: Drug Repurposing Portal

IntelGenx Corp. announced that when montelukast sodium delivered through the VersaFilm system, it offers a unique drug repurposing opportunity for the treatment of degenerative diseases of the brain, such as mild cognitive impairment and Alzheimer's disease, the most prominent form of dementia. First developed by Merck in Montreal, montelukast sodium (trade name Singulair) is registered for the treatment of asthma and seasonal allergies.


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Towards precision medicine-based therapies for glioblastoma: interrogating human disease genomics and mouse phenotypes

August 22nd 2016, Posted by: Drug Repurposing Portal

In this study, a novel GBM (glioblastoma) drug repositioning strategy leveraging both lower-level diseases and drug genomics, and higher-level mouse phenotypes was developed. GBM-specific mouse phenotypes was identified using a compiled list of GBM-associated genes identified from multiple TCGA studies. Further, all the FDA-approved drugs for candidates that share similar mouse phenotype profiles with GBM were screened. This approach was validated using approved GBM drugs and the performance was approximated by detecting novel GBM drugs using two evaluation sets: a set of potential GBM therapies tested in clinical trials and a set of off-label GBM drugs in the post-marketing surveillance system. Top 10% drug predictions were taken into consideration. In a nutshell, the study combines both the genomic and phenotypic data for diseases and drugs towards identifying novel targeted therapies for GBM.


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A genomics-based systems approach towards drug repositioning for rheumatoid arthritis.

August 22nd 2016, Posted by: Drug Repurposing Portal

Novel approach to re-purpose drugs for Rheumatoid Arthritis (RA). With disease-disease and drug-disease network as background data, the proposed algorithm uses network based prioritization approach to re-purpose drugs for RA.


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Paradigm Biopharmaceuticals Ltd clears initial safety review of nasal spray

August 19th 2016, Posted by: Drug Repurposing Portal

Paradigm Biopharmaceuticals is repurposing pentosan polysulfate sodium (PPS) for respiratory diseases including allergic rhinitis and allergic asthma, as well as for bone marrow edema lesions following traumatic injury. PPS is a well-established mild anticoagulant and anti-inflammatory agent that has been used for over 60 years.


News Methods Funding Collaborations

Insight from behind the lab bench: Could a period pain treatment be re-purposed to treat Alzheimer's disease?

August 19th 2016, Posted by: Drug Repurposing Portal

Mefenamic acid is only available by prescription and is prescribed largely to treat period pain. Drug can inhibit the inflammasome and prevent release of inflammatory cytokines in the cells. The commercially available drug mefenamic acid was able to inhibit the inflammasome and reduce memory loss in both mouse and rat models of Alzheimer's-like memory deficits.


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