Drug Repurposing News



Repurposing metformin for improving survival in patients with grade III glioma

August 9th 2018, Posted by: Drug Repurposing Portal

A new study has found that the antidiabetic drug metformin can inhibit high-grade glioma growth in vitro and in vivo. A multivariate adjusted Cox-regression analysis was done to evaluate survival in patients with high-grade gliomas (WHO grade III and IV), with or without administering metformin. The overall and progression-free survival after metformin treatment improved significantly in patients with WHO grade III gliomas. However, this effect was not observed in patients with WHO grade IV gliomas. Thus, repurposing metformin for high-grade gliomas could offer potential therapeutic benefits in terms of enhanced progression-free survival.


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Anaesthetic agent Ketamine to be repurposed for Parkinson's patients

August 4th 2018, Posted by: Drug Repurposing Portal

A small phase I clinical trial supported by a three-year $750,000 grant from the Arizona Biomedical Research Commission (ABRC) is planned this summer at the UA College of Medicine - Tucson by Dr. Sherman and Torsten Falk from the Department of Neurology to test ketamine, a drug currently used to treat pain and depression, in reducing the uncontrollable involuntary movements induced by levodopa in Parkinson's disease. The trial intends to treat ten Parkinson's patients with ketamine once a month for about 6 hours, while they continue taking their prescribed medications. This study would thus establish the utility of ketamine, after nearly five decades, as a repurposed drug for several other medical conditions.


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Repurposing potential of fluvastatin in liver steatosis

August 2nd 2018, Posted by: Drug Repurposing Portal

Sirtuins belong to a family of NAD+-dependent deacetylase enzymes. Sirtuin 6 (SIRT6) has been implicated in cancer suppression, aging and other metabolic diseases including hypercholesterolemia and type 2 diabetes. Current study hypothesized that SIRT6 can be crucial to be targeted in patients with liver steatosis as its expression is abundant in liver. On these lines, authors have identified antilipemic agent fluvastatin as a potential SIRT6 activator by drug repositioning. Furthermore, the group also evaluated fluvastatin modulated mechanisms to regulate cholesterol homeostasis and proposed the prospective use of fluvastatin in fatty liver disease.


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Old drug repositioning and discovery of proteasomal deubiquitinating enzyme inhibitors for cancer therapy

August 1st 2018, Posted by: Drug Repurposing Portal

The ubiquitin proteasome system is an established target of cancer therapies, evident by the presence of US-FDA approved anticancer 20S proteasome inhibitors. Deubiquitinating enzymes (DUBs), an essential component of the ubiquitin proteasome system, regulate cellular processes through the removal of ubiquitin from ubiquitinated-tagged protein, and are linked to cancer and other pathologies. The study of proteasomal DUBs and their inhibitors has garnered interest as a novel strategy for cancers resistant to 20S proteasome inhibitors. Based on discovery through rational design approach, from searching natural products, and from repurposing old drugs, the current study offers a future perspective for the therapeutic role of DUBs.


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Copper deficiency disorders could be tackled by repurposing anticancer drugs

August 1st 2018, Posted by: Drug Repurposing Portal

Inherited mutations that prevent copper delivery to a key mitochondrial enzyme perturb energy production and result in fatal mitochondrial diseases. While no therapy exists currently for these disorders, a research team from Texas A&M AgriLife research has found that copper metabolism deficiencies can be addressed by more targeted treatment options. The team found that the clinical candidate elesclomol can mimic the missing transporters of copper. While elesclomol has undergone multiple human clinical trials, the current findings offer an exciting possibility of repurposing this anticancer drug for the treatment of copper metabolism disorders.


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Overcoming drug-resistant cancer cells by repurposing antipsychotic drugs

July 30th 2018, Posted by: Drug Repurposing Portal

A new research from Penn State Cancer Institute has proposed that two drugs presently being ued to treat psychosis and depression, perphenazine and fluphenazine, showed anti-cancer activity in mice by blocking the movement of cholesterol within drug-resistant cancer cells. Perphenazine could reduce tumor growth by decreasing cholesterol metabolism in cancer cells. By encapsulating perphenazine into a nanoparticle, its capability of crossing into the brain could be prevented, and its new function to stop cancer growth could be enhanced. Hence new strategies to repurpose antipsychotics in drug-resistant cancer cells could be explored.


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Repurposing cholesterol control drug Gemfibrozil for dementia and brain inflammation

July 26th 2018, Posted by: Drug Repurposing Portal

The Drug Discovery program of the Alzheimer's Society is endeavouring to find new treatments for Alzheimer's disease related dementia in half the time it takes to develop a brand new drug. The cholesterol controlling drug Gemfibrozil was shown to reduce amyloid protein deposits and brain inflammation in pre-clinical studies on mice. With over 850,000 people living with dementia in the UK today, this number is only expected to rise up to 1 million by 2021. Repurposing drugs for Alzheimer's is important to take us a step closer to treat this devastating condition.


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JNK inhibitors to the rescue of Alopecia Areata - not all is lost yet

July 26th 2018, Posted by: Drug Repurposing Portal

A major breakthrough in the world of hair loss due to Alopecia Areata (AA) is the development of targeted therapies using FDA-approved, small molecule Janus-kinase or JAK inhibitors, often used for treating various cancers and autoimmune disorders. A recent review summarizes the prospects and benefits of utilizing JAK inhibitors in preclinical and clinical studies on AA. With an advancement in understanding molecular mechanisms of AA pathogenesis, repurposing JAK inhibitors to treat, and perhaps even effectively reverse mild to severe hair loss in men and women, is no longer a distant dream.


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Finding a new use for antimalarial drug Quinine in Dengue

July 25th 2018, Posted by: Drug Repurposing Portal

The rise in the global economic burden and mortality rates due to dengue virus (DENV) disease outbreaks continues with no sign of an approved treatment for the virus. A new study by researchers from Thailand evaluated four FDA-approved drugs - aminolevullic acid, azelaic acid, mitoxantrone hydrochloride, and quinine sulfate for their ability to inhibit DENV replication. Among the four, quinine, commonly used for treating malaria and babesiosis, was found to be the most effective in inhibiting DENV replication, and hence viral production in three different human cell lines tested. The results suggest an antiviral effect of quinine and its capability to treat DENV diseases.


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Drug for hypertension and angina pectoris enters phase 2b of clinical trials for Huntington's disease

July 17th 2018, Posted by: Drug Repurposing Portal

SOM Biotech announced a phase 2b clinical trial for Huntington's disease (HD) for SOM3355, a drug originally indicated for hypertension and angina pectoris. SOM3355 is a potent selective inhibitor of vesicular monoamine transporter-2 (VMAT2). It causes a decrease in the levels of dopamine and reduces movements associated with HD. SOM3355 reduces choreic movements associated with HD by decreasing dopamine levels, an essential neurotransmitter involved in the control of coordinated movements.


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Metformin could be repurposed to mitigate prostate cancer progression

July 16th 2018, Posted by: Drug Repurposing Portal

A recent pre-clinical study published in Clinical Cancer Research has proposed that the oral anti-diabetic drug Metformin is capable of inhibiting progression of prostate cancer. Using a transgenic adenocarcinoma of the mouse prostate (TRAMP) model, the authors found that targeting infiltrating tumor-associated macrophages, especially those induced by androgen deprivation therapy (ADT), caused a significant decrease in inflammation-associated prostate carcinogenesis and metastasis. Further investigations are required before combining ADT and metformin as an effective clinical treatment strategy for prostate cancer at different stages.


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Repurposing potential of Amiodarone against Ebola virus

July 16th 2018, Posted by: Drug Repurposing Portal

Currently, there are no FDA approved vaccines or drugs for the prevention and treatment of Ebola virus infection. Drug repurposing or repositioning is a promising approach to identify FDA approved drugs as prospective therapeutic approaches for diseases due to Ebola virus. Amiodarone is a drug approved for treating cardiac arrhythmia. A recent study reported its antiviral activity against Ebola virus in vitro. Further in vitro and in vivo testing to evaluate the anti-Ebola activity of amiodarone are warranted for its successful repurposing.


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Review of drug repurposing to develop anticancer agents

July 13th 2018, Posted by: Drug Repurposing Portal

Off-target effects of drugs provide meaningful insights for systematic drug purposing. Diverse targets are associated with cancer pathogenesis due to heterogeneity of the disease. Therefore, several of already known drugs that interfere with these targets could be repurposed as anti-cancer agents. This recently published article provides a comprehensive review of all the recent repurposing efforts to develop novel anti-cancer strategies.


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Prediction and population-based validation of In silico drug repurposing through network-based approaches

July 12th 2018, Posted by: Drug Repurposing Portal

A new study published in Nature Communications has identified hundreds of new drug-disease associations for over 900 FDA-approved drugs by quantifying the network proximity of disease genes and drug targets in the human (protein-protein) interactome. To test their causal relationship, the authors selected four network-predicted associations from large healthcare databases of more than 220 million patients and pharmacoepidemiologic analyses. The study underscores that drug repurposing could be facilitated through the unique integration of protein-protein interaction network proximity and large-scale patient-level longitudinal data complemented by mechanistic in vitro studies.


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Repurposing antihypertensive drug Verapamil to manage type 1 diabetes

July 9th 2018, Posted by: Drug Repurposing Portal

Verapamil indicated for the management of hypertension could help stabilize blood sugar levels in patients with type 1 diabetes. A recent study published in Nature Medicine found that verapamil, which blocks calcium channel activity, was also shown to reduce TXNIP levels, stopping the loss of beta cells in type 1 diabetes patients. A phase II (NCT02372253) clinical trial conducted in 24 adult patients who had developed type 1 diabetes in the past three months showed that if verapamil was taken alongside insulin, their requirement for daily insulin reduced and the patients had fewer episodes of hypoglycemia with a good control of blood sugar levels.


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Altitude sickness drug appears to slow progression of glioblastoma

July 9th 2018, Posted by: Drug Repurposing Portal

A recent study published in the journal of Science Translational Medicine reported that the drug acetazolamide, often used to treat altitude sickness, can also be used in combination with temozolomide (TMZ) to treat glioblastomas. Adding acetazolamide to TMZ therapy enabled mice with gliomas to survive longer by modulating the response to therapy. The authors thus suggest that repurposing acetazolamide along with temozolamide as a combination therapy might be an effective treatment strategy in a subgroup of glioblatoma patients with tumors having high BCL-3 expression.


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Antifungal effects of tricyclic antidepressants on Candida albicans growth

July 7th 2018, Posted by: Drug Repurposing Portal

The opportunistic pathogenic yeast Candida albicans forms biofilms on solid surfaces and causes candidiasis in humans. Biofilms not only develop tolerance to commonly used medical interventions, but also acquire resistance to antifungals. While some evidence points out that certain antidepressants may have antibacterial properties, not much is known about their antimycotic effects. A recent research study from Italy demonstrated that the tricyclic antidepressants (TCAs) doxepin, imipramine, and nortriptyline could inhibit C. albicans growth and biofilm formation, confirming their antimicrobial effects. These observations thus provide a basis to devise new drug repositioning strategies for TCAs and exploit their capabilities as potential antimycotic agents.


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Using drug repurposing to identify novel antibiotics

July 5th 2018, Posted by: Drug Repurposing Portal

Emergence of multidrug-resistant bacterial infections (MDRBIs) has led to an urgent necessity to develop new antibiotics. The current article provides a comprehensive review of drug repurposing-based antibiotic development strategies between 2016-2017. It also provides details of recent FDA-approved antibiotics and antibiotics in developmental pipeline. Antibacterial properties of different therapeutic classes of FDA-approved drugs such as anti-cancer, anti-fungal, anti-hyperlipidaemia agents are also discussed in this interesting review. Another feature highlighted in the review is the importance of combination therapies with existing antibiotics to combat MDRBIs.


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Repurposing Metformin as a possible anti-fibrotic therapy

July 5th 2018, Posted by: Drug Repurposing Portal

A new pre-clinical study from the University of Alabama at Birmingham has determined that the debilitating effects of lung fibrosis could possibly be resolved through the non-insulin dependent diabetes drug metformin. Mouse models of idiopathic pulmonary fibrosis (IPF) administered metformin showed signs of improved and accelerated resolution of the disease in a span of 3 weeks. The research needs to be extended to studies in human patients with IPF in the near future, in order to determine the suitability of metformin as a repurposed drug to treat chronic IPF.


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Potential therapeutic repositioning of GV1001 for benign prostatic hyperplasia

July 5th 2018, Posted by: Drug Repurposing Portal

Male reproductive disorders such as benign prostatic hyperplasia (BPH) are in urgent need of alternate drugs which could overcome side effects of prescribed drugs and exhibit improved therapeutic efficacy. The present study explores the potential antioxidant effect of GV1001, a telomerase-derived peptide vaccine, against testosterone-induced BPH in rats. Further studies are warranted to understand the precise mechanisms by which GV1001 confers protection in BPH, and for successfully repositioning it for future clinical applications.


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The ACE inhibitor Captopril may possibly be repurposed to treat primary myelofibrosis

July 4th 2018, Posted by: Drug Repurposing Portal

Primary Myelofibrosis (MF) is a form of chronic blood cancer characterized by excess scar tissue formation in the bone marrow, leading to impaired production of normal blood cells. Although current treatment options include curative allogenic stem cell transplantation and palliative use of JAK2 inhibitor ruxolitinib, yet there is an urgent need to find alternate therapies. A recent study suggests that the angiotensin-converting enzyme (ACE) inhibitor captopril, commonly used for treating hypertension and congestive heart failure, could potentially mitigate the development of the disease in a murine model of MF. Results of this study warrant further clinical validation in patients suffering from MF, and a possible repositioning of captopril.


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Antihistamines can be repurposed as potential antiviral therapeutics for Ebola

July 4th 2018, Posted by: Drug Repurposing Portal

The Ebola and Marburg filoviruses can cause severe hemorrhagic fevers, and have no known FDA-approved vaccines or therapeutic options. The authors of the current study have identified common over-the-counter antihistamines such as diphenhydramine (Benadryl) as potential antiviral therapeutics against these filoviruses. They found that the H1-specific antihistamines could inhibit the entry of these viruses into cells through endosomes and not through conventional histamine receptors. The study opens the possibilities to explore new repurposing options using pre-existing drugs for diseases with no known treatment.


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Drug-repurposing and other strategies to treat Fibrosis

July 3rd 2018, Posted by: Drug Repurposing Portal

The current perspective comprehensively summarizes various aspects of fibrosis and its treatment, including a focus on (a) common biological pathways involved in fibrosis of different organs, and (b) review of therapeutic agents from preclinical to approved stages of development. Strategies that can improve treatment response of therapeutic molecules such as combination approaches and indirect modulators are also discussed in this study.


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Low-dose aspirin for treating Alzheimer's disease

July 2nd 2018, Posted by: Drug Repurposing Portal

A major hallmark of Alzheimer's disease (AD) is the increased accumulation of amyloid beta plaques in the brain. Activation of cellular machinery that would assist in clearing up this toxic build-up could be a promising strategy for slowing the disease progression. Along these lines, a study recently published in the Journal of Neuroscience proposes that the commonly used NSAID pain-reliever aspirin could potentially reduce AD pathology. The authors found that oral administration of a low-dose regimen of aspirin decreased cerebral plaque load in a mouse model of AD by activating peroxisome proliferator-activated receptor α (PPAR α), and triggering enhanced lysosomal biogenesis, the organelles responsible for clearing cellular debris. These observations underscore the multi-therapeutic benefits of aspirin, and the significance of repurposing it for diseases such as Alzheimer's as well as lysosomal storage disorders.


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Veterinary flea and tick drugs could prevent outbreaks of malaria and Zika virus infection

July 2nd 2018, Posted by: Drug Repurposing Portal

Drugs called isoxazolines, which include fluralaner (Bravecto) and afoxolaner (NexGard), are sold as veterinary products and are commonly used to protect pets from fleas and ticks. A new research study by TropIQ's Koen Dechering and Calibr's Matt Tremblay has determined via experimental studies on mosquitos and computer modelling that the two drugs fluralaner and afocolaner could potentially kill disease-carrying mosquitos. The results of the study thus provide insights on new ways of repurposing the veterinary flea and tick drugs to prevent outbreaks of malaria and Zika virus.


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Can psychedelics be repurposed as antidepressant drugs?

July 1st 2018, Posted by: Drug Repurposing Portal

Researchers at the Imperial College London are planning for a large trial of at least two years to compare the "healing powers" of the psychedelic prodrug compound psilocybin (magic mushroom compound) with a leading antidepressant escitalopram, a selective serotonin reuptake inhibitor (SSRI). A previous study found that psilocybin reduced depression in 80% of terminally-ill cancer patients. Another study demonstrated that psilocybin when combined with cognitive behavioural therapy was more effective at making people quit smoking than current treatments. Several published studies have shown that psilocybin affected two areas of the brain: the amygdala, which is heavily involved in processing emotions such as fear and anxiety, and the default-mode network - a collaboration of different brain regions. Thus, the study hints at the potential useof psilocybin to address several mental health problems.


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Drug repositioning in drug discovery for infectious diseases

June 28th 2018, Posted by: Drug Repurposing Portal

Simultaneous decrease in the number of approved antibiotics and a steady increase of multidrug resistance points towards the need to develop novel antimicrobial treatment strategies. This review summarizes the repositioning potential of non-antibiotic drugs for antibacterial treatment. Various scientific studies demonstrated the antimicrobial activities of drugs of several pharmacological classes including psychotropics, local anaesthetics, tranquilizers, cardiovascular drugs, antihistamines, and anti-inflammatories. Hence, it can be inferred that the repositioning of non-antibiotic drugs with known toxicity profiles represents a promising alternative for the treatment of bacterial infections.


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Clinical trials and therapeutic rationale for drug repurposing in schizophrenia

June 26th 2018, Posted by: Drug Repurposing Portal

The major challenges in schizophrenia treatment include high rates of treatment resistance and associated refractory symptoms, thus suggestive of the need for novel therapeutic strategies. The present study reviews the historical role of drug repurposing in schizophrenia drug discovery. This study also highlights the main classes of repurposing candidates currently in clinical trials for schizophrenia with respect to their therapeutic rationale, mechanisms of action, and preliminary results from clinical trials. Additionally, this review also summarizes the challenges and limitations of repurposing in schizophrenia, and outlines the novel techniques that might be useful in addressing treatment challenges/limitations.


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Integrative approaches to identify drug repurposing/repositioning candidates for Alzheimer's disease

June 23rd 2018, Posted by: Drug Repurposing Portal

Despite extensive research, there are no effective therapies for Alzheimer's disease (AD). The current study adopted integrative approaches to identify novel therapeutic opportunities. AD case-control studies were analysed using master regulator and two-tail gene set enrichment analyses to identify key AD-associated targets like CNOT7, CSRNP2, SLC30A9, and TSC22D1. In the next step, a Connectivity Map Adaptation suggested drug repurposing/repositioning of FDA approved drugs Cefuroxime, Cyproterone, Dydrogesterone, Metrizamide, Trimethadione, and Vorinostat as prospective treatment options for AD.


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In search of potential molecular targets and drug repositioning candidates for Alzheimer's disease

June 23rd 2018, Posted by: Drug Repurposing Portal

Alzheimer's disease (AD) is a complex neurodegenerative disease involving impairment of several key molecular mechanisms. Using a transcription factor-centered regulatory network reconstruction, the authors of the current study identified various molecular targets and six drug candidates that could be repositioned in AD. The study not only provides new perspectives on molecular targets and drug therapies for future investigation and validation in AD, but also underscores the importance of bioinformatic tools as exploratory strategies for drug repurposing in other neuropathologies.


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Repurposing potential of fingolimod as novel therapeutic strategy for temporal lobe epilepsy

June 22nd 2018, Posted by: Drug Repurposing Portal

Temporal lobe epilepsy (TLE) is a serious neurological condition that shares distinct pathogenetic aspects with multiple sclerosis (MS). Based on this concept, authors of the present study investigated the repurposing potential of MS drug fingolimod for TLE. Expression of fingolimod target sphingosine-phosphate receptors is augmented in experimental TLE mouse models. In line, transient fingolimod treatment of TLE mouse revealed substantial reduction of chronic seizure activity and demonstrated neuroprotective and anti-gliotic effects. Together, these data suggest repurposing fingolimod as a novel therapeutic alternative in focal epilepsies.


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Promising cancer drugs could be repurposed to treat tuberculosis

June 22nd 2018, Posted by: Drug Repurposing Portal

A recent study showed that promising experimental chemotherapy drugs (myeloid leukemia cell differentiation protein Mcl-1 inhibitors) may help to knock out another life-threatening disease: tuberculosis (TB). Investigators showed that pre-clinical Mcl-1 inhibitors significantly inhibited Mycobacterium tuberculosis (Mtb) growth in human macrophages and multicellular granuloma structures. Treating Mtb infected macrophages with Mcl-1 inhibitors could induce apoptosis of Mtb-infected cells, and subsequently reduce Mtb growth. This in turn resulted in less inflammation and damage to the lungs and increased control of TB. These data suggest that we can capitalize on repurposing promising cancer drugs for the treatment of TB.


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Systems biology analyses for biomarker identification and drug targeting in Head and Neck Cancers

June 22nd 2018, Posted by: Drug Repurposing Portal

Robust biomarkers and effective diagnostics still remain unavailable for head and neck squamous cell carcinoma (HNSCC). An in-depth systems biology approach was adopted in the current study to identify biomarker signatures for drug targeting in HNSCC. Eleven proteins, five transcription factors, and twenty microRNAs were identified as potential drug targets. Using geneXpharma, a transcriptome guided drug repositioning tool, several candidate drugs were repurposed to these potential targets, including antineoplastic agents gemcitabine and irinotecan, antidiabetics such as rosiglitazone, dermatological agents like clocortolone and acitretin, and antipsychotics such as risperidone. Further experimentation is warranted on these molecular signatures and repurposed drugs for the clinical management of HNSCC.


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Repurposing vs new drug: future of drug discovery

June 21st 2018, Posted by: Drug Repurposing Portal

A new scientific paper with the word repurposing in the title appears nearly every day. With drug repurposing recieving so much attention and funding, this article discusses about the pros and cons of drug repurposing vs new drug discovery, putting into persepctive the importance of both the approaches for future drug discovery endeavours.


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Comprehensive overview of drug discovery for Zika virus infection

June 20th 2018, Posted by: Drug Repurposing Portal

Zika virus (ZIKV) infection has emerged as a potential global threat to human health. Lack of approved treatments point towards the necessity of developing effective therapeutic strategies rapidly. The present review summarizes the A-Z of the recent advances in ZIKV drug discovery efforts, highlighting the importance of drug repositioning and computationally guided compounds, including discovered viral and host cell inhibitors. Promising ZIKV molecular targets as well as targets belonging to the host cell are described as possible new opportunities for ZIKV drug discovery.


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The effectiveness of pan-ERBB inhibitor afatinib in potentially treating K-RAS-driven NSCLC

June 20th 2018, Posted by: Drug Repurposing Portal

Afatinib is mainly used to treat cases of NSCLC that harbour mutations in the epidermal growth factor receptor (EGFR) gene. The present study provides evidence that EGFR signaling is engaged in K-RAS-driven lung tumorigenesis, and the pan-ERBB inhibitor afatinib can be repositioned to target K-RAS-driven NSCLC.


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Repurposing the antihypertensive drug- L-Captopril as an antibiotic

June 18th 2018, Posted by: Drug Repurposing Portal

This study evaluates the potency of L-Captopril, a well known angiotensin-converting enzyme inhibitor, as an antibiotic. The microbial enzyme DapE is an important enzyme for bacterial survival. Derivatives of L-Captopril were tested for DapE inhibition activity, in order to find the most appropriateof all that could functionally be used as an antibiotic.


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Blocking TLR4-associated inflammation in osteoarthritis could be a new strategy for drug repurposing

June 16th 2018, Posted by: Drug Repurposing Portal

Rheumatic diseases such as osteoarthritis (OA) are becoming huge economic burdens to the health system. No efficient treatments exist despite the growing knowledge in OA pathophysiology. Chondrocytes mediate inflammation in OA, which manifests when innate immune receptors such as Toll-like receptor 4 (TLR4) are activated by damage-associated molecular patterns (DAMPS). Drugs targeting TLR4-mediated inflammatory responses might be therapeutically beneficial, but are currently unavailable. The current study underscores the importance of repurposing clinically approved drugs such as amitriptyline, naloxone and thalidomide to manage and treat TLR4-mediated OA cartilage inflammation.


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The 7th Annual Drug Repositioning, Repurposing and Rescue Conference highlighted the benefits of Artificial Intelligence in Drug Repurposing

June 14th 2018, Posted by: Drug Repurposing Portal

The 7th Annual Drug Repositioning, Repurposing and Rescue Conference held between June 26-27 at the Wyndham Grand Chicago Riverfront featured Artificial intelligence (AI) as one of the key themes to be explored by pharma executives, academicians, researchers and patient advocacy groups for exploring its role to improve the efficiency and success rates of drug development, testing and approvals. Some of the world's foremost leaders in AI shared key learnings and technological advancements in AI at the conference, with an objective to encourage the attendees to implement this knowledge into their current drug repurposing efforts across pharma, academia and research.


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"Soft vs hard" drug repurposing - a comparative landscape in precision oncology

June 14th 2018, Posted by: Drug Repurposing Portal

Drug repurposing is at the core of precision oncology. Adoption of genomic- or actionable-target treatments vis-a-vis tissue- or cancer-specific treatments necessitates the reuse of anti-cancer drugs meant for one cancer type to treat other cancer types. But most cancers are genetically complex, hence limiting the search of suitable agents to existing oncological drugs would hinder the discovery of potential pharmacological agents from other disease areas. If existing oncological drugs are profiled for re-use on new indications as "soft repurposing," then the application of non-cancer drugs as anti-cancer medications maybe termed "hard repurposing", albeit with multiple challenges in precision oncology.


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FDA orphan drug designation for AMO Pharma's AMO-04 in the treatment of Rett Syndrome

June 13th 2018, Posted by: Drug Repurposing Portal

The US-FDA has granted orphan drug status to AMO Pharma Limited's ("AMO Pharma") investigational therapeutic molecule AMO-04 for the treatment of Rett syndrome, a rare childhood neurodevelopmental disorder. AMO-04 is a glutamate modulator that has shown early-stage promise in the treatment of Rett syndrome. Additional research conducted by Numedicus, a private biopharmaceutical company that focuses on repurposing drugs, also indicated that AMO-04 could benefit patients suffering from certain breathing disorders.


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Epilepsy drug VX-765 could be repurposed to treat Multiple Sclerosis

June 13th 2018, Posted by: Drug Repurposing Portal

A recent study by researchers from the University of Alberta has found that VX-765, a drug used clinically to treat epilepsy, could potentially inhibit pyroptosis, a type of programmed cell death associated with inflammation in oligodendrocytes. As oligodendrocytic cell death is a hallmark of multiple sclerosis (MS), the researchers proposed that VX-765 could be repurposed to treat MS.


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Repositioning of anti-diabetic Omarigliptin as a once-weekly intranasal antiparkinsonian agent

June 12th 2018, Posted by: Drug Repurposing Portal

While most gliptins do not cross the blood brain barrier (BBB), the once-weekly anti-diabetic DPP-4 inhibitors omarigliptin (OG) and trelagliptin (TG) could successfully cross the BBB, as revealed in a new study. LC-MS/MS methods used in the study estimated levels of OG and TG in the plasma and brain tissues of rats to determine their BBB penetratibility and check the possibility of repositioning them as antiparkinsonian agents. A novel intranasal formulation of lipophilic OG with penetration enhancing and anti-microbial properties was developed. OG crossed the BBB successfully after oral administration or via the intra-nasal route, suggestive of repositioning it as a promising antiparkinsonian agent.


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FDA approves cancer drug Rituximab for treating Pemphigus Vulgaris

June 8th 2018, Posted by: Drug Repurposing Portal

FDA approved Genentech's innovator rituximab (Rituxan), a monoclonal antibody acting against CD20 antigen, for the treatment of adults with moderate to severe pemphigus vulgaris (PV). In total, the reference product is now licensed to treat 6 diseases: non-Hodgkin's lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis, and PV, thus paving the way for multiple repurposing of rituximab in various diseases.


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Promising ways to overcome legal and regulatory barriers to drug repurposing

June 8th 2018, Posted by: Drug Repurposing Portal

Drug repurposing is an alternative strategy to develop new drugs for known diseases, and has comparatively fewer risks, lower costs, and shorter timelines. However, owing to multiple legal and regulatory bottlenecks, the complete potential of this strategy has been underutilized. The current review highlights the limitations of these barriers and discusses potential solutions for them.


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Repurposing Statins: From anti-cholesterol oral therapy to inhaled anti-inflammatory formulations

June 8th 2018, Posted by: Drug Repurposing Portal

Statins are lipid lowering drugs traditionally used to manage cardiovascular diseases. Recent studies have identified several pleiotropic properties of statins such as anti-inflammation, anti-oxidantion, and muco-inhibition that may be beneficial for targeting chronic inflammatory lung diseases. This review discusses the potential use of statins as inhaled anti-inflammatory drug formulations to target lung diseases.


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Antidepressant drug Sertraline repurposed to sensitize lung cancer cells to Erlotinib

June 7th 2018, Posted by: Drug Repurposing Portal

A major challenge in lung cancer treatment is the development of drug resistance, which is suggestive of a huge unmet medical need. Using a medical genetics-based approach, the current study showed that the approved anti-depressant drug sertraline could inhibit viability of non-small cell lung cancer (NSCLC) cells, and showed a synergistic effect with erlotinib. The combination of sertraline and erlotinib effectively suppressed tumor growth in a NSCLC mouse model, thereby demonstrating the potential of sertraline repurposing in lung cancer treatment.


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Finding potential drug targets through a new "genetic atlas" of plasma proteins

June 7th 2018, Posted by: Drug Repurposing Portal

A team of scientists from the University of Cambridge and Merck & Co. has created a "genetic atlas" of genetic links that could help reveal biomarkers for potential drugs. About 3,600 proteins were measured in blood samples from 3,300 people out of which 1,927 genetic associations with 1,478 proteins were successfully identified. By linking genetic factors to diseases via specific proteins, the analyses highlights potential therapeutic targets, opportunities for matching existing drugs with new disease indications, and potential safety concerns for drugs under development. With this genetic map, the study has identified specific biological pathways that lead to Crohn's disease and eczema.


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Inhalation of Interferon-γ to treat lung diseases

June 7th 2018, Posted by: Drug Repurposing Portal

Interferon-γ (IFN-γ) is currently delivered as a subcutaneous injection to inhibit fibrotic pathways for treating chronic granulomatous disease and osteoporosis. This study evaluates repositioning of IFN-γ as an inhaled aresol to treat pulmonary diseases such as Tuberculosis and Idiopathic Pulmonary Fibrosis.


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Niclosamide, an anti-helmenthic with potential to treat multiple diseases

June 6th 2018, Posted by: Drug Repurposing Portal

Niclosamide has been traditionally used to treat tapeworm infections. The present study however highlights multiple pharmacological activities of niclosamide to treat a broad spectrum of diseases such as neurodegenerative diseases (Parkinson's disease) and metabolic disorders (Diabetes).


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Repurposing the carbonyl scavenger Hydralazine as pharmacotherapy in degenerative disease

June 6th 2018, Posted by: Drug Repurposing Portal

Spontaneous oxidation damages unsaturated lipids, generating numerous electrophilic carbonyl compounds that readily attack cell macromolecules, and form adducts that potentially drive tissue dysfunction commonly seen in many degenerative conditions. Using animal models of such disorders, researchers have analyzed the efficacy of nucleophilic carbonyl-trapping drugs with the premise that they will confer protection to tissues by preventing formation of toxic lipid-derived electrophiles (LDEs) within cells. The current study hence explores the importance of the broad-spectrum, clinically-approved carbonyl scavenger hydralazine in trapping multiple LDEs in two different yet significant conditions that produce LDE, namely spinal cord injury and alcoholic liver disease. aThus the study aims to ddresses two obstacles that hamper clinical translation of LDE-trapping therapies while also suggesting potential strategies to overcome these problems.


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Arsenic as an arsenal to fight cancer

June 5th 2018, Posted by: Drug Repurposing Portal

Arsenic is commonly known more as a toxic substance than as a cancer drug. Low doses of arsenic trioxide have shown a 95% remission rate in acute promyelocytic leukemia (APL), as well as slow down the growth of other cancers. However, conventional arsenic delivery methods have not been successful in solid tumors of the breast, lung, ovaries and elsewhere due to arsenic toxicity. To overcome this challenge, a nanobins (liposome)-mediated arsenic delivery mechanism into blood stream was developed, which would release arsenic only upon reaching cancer cells, thereby eliminating them specifically.


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Evolving trends in computational drug repositioning

June 5th 2018, Posted by: Drug Repurposing Portal

Sir James Black, a Nobel Prize-winning pharmacologist, advocates that the most fruitful basis for the discovery of a new drug is to start with an old drug. Rational design of drug mixtures is however challenging due to absence of or limited information about cell regulation and mechanisms of in vivo pathway activation and interactions. Most drugs repositioned successfully were discovered serendepitously during late phase clinical studies of unexpected but beneficial findings. The current study summarizes and discusses promising bioinformatics approaches and pipelines for computational drug repositioning through multi-domain pharmacomodules pharmacologically relevant sub-networks of biomolecules and/or pathways from a collection of databases by independent/simultaneous mining of several datasets.


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A sweet medicine for Alzheimer's disease

June 5th 2018, Posted by: Drug Repurposing Portal

Alzheimer's disease (AD) is a neurodegenerative disorder involving multiple pathogenic signaling pathways. The present study identified an FDA approved sweetener, neohesperidin dihydrochalcone (NHD), as a potential multi-target inhibitor of AD, paving the way for developing new repurposing strategies for AD therapy.


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ChemMaps, a new online tool that supports drug repurposing activities

June 4th 2018, Posted by: Drug Repurposing Portal

ChemMaps (ChemMaps.com) is a new online service created by researchers of North Carolina State University. This websever features more than 8,000 drugs and over 47,000 environmental chemicals. Interestingly, users can interactively navigate the chemical space of listed drugs or compounds in 3D in real-time. Moreover, this online tool is helpful to better understand the chemical neighborhood of a particular compound which is supportive for drug repurposing related activities or chemical risk assessment.


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Hepatitis C drug could be repurposed to treat Zika virus infection

June 4th 2018, Posted by: Drug Repurposing Portal

Stem cell researcher Alysson Muotri and his team at UC San Diego School of Medicine compared the genomes of the Hepatitis C and the Zika viruses, and noticed the similarities they shared in their replication regions through their study. The team found that the Hepatitis C drug sofosbuvir was capable of killing the Zika virus too, and confer protection to human brain stem cells. Tests conducted on animal models of Zika virus infection confirmed these results. Since the drug is already in the market, clinical trials to test sofosbuvir for treating and perhaps curing Zika virus infected individuals could be expedited and thus adopted as a promising drug repurposing strategy.


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Denovo Biopharma acquires license for novel application of its small molecule DB102 to treat Pulmonary Arterial Hypertension

June 3rd 2018, Posted by: Drug Repurposing Portal

Denovo Biopharma LLC has entered into an exclusive global license agreement with the Stanford University School of Medicine that will enable Denovo to develop and commercialize its lead compound DB102 (enzastaurin) for treating pulmonary arterial hypertension (PAH) and emphysema. DB102, an orally available investigational small molecule, is a serine/threonine kinase inhibitor of the PKC beta and AKT pathways with orphan drug status in diffuse large B-cell lymphoma (DLBCL) and glioblastoma multiforme (GBM) and potential to treat solid and hematological cancers. Denovo is currently conducting a global Phase 3 trial to evaluate the efficacy of DB102 plus R-CHOP in patients with high risk DLBCL.


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Plant growth regulator Abscisic Acid repositioned as a potential anti-fungal agent

June 3rd 2018, Posted by: Drug Repurposing Portal

Treatment options for fungal infections are very limited due to lack of diverse therapeutic agents as well as adverse effects of the current antifungal agents. Here, abscisic acid is proposed as a potential anti-fungal agent using drug repositioning strategies. Both in silico and in vitro anti-fungal methods were used as tools to select and validate abscisic acid repurposing.


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Multiple sclerosis drug Fingolimod could reduce chemotherapy-induced adverse events

June 3rd 2018, Posted by: Drug Repurposing Portal

Recent study found that Fingolimod (sold as Gilenya), an FDA-approved therapy for multiple sclerosis, could reduce chemotherapy-induced side effect peripheral neuropathy (CIPN). CIPN is an immense unmet medical need presented by 40% of multiple myeloma and mantle cell lymphoma patients treated with Bortezomib. Interestingly, recent studies demonstrated that Fingolimod inhibits Bortezomib-induced accumulation of sphingosine 1-phosphate and dihydrosphingosine 1-phosphate and subsequent neuroinflammation and enhanced release of the excitatory neurotransmitter glutamate involved in pain. Together, these data suggest repurposing of Fingolimod as an adjuvant to Bortezomib for the prevention and treatment of chemotherapy-related neurotoxicity.


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Repurposing diabetes drug metformin to treat heart and circulatory diseases

June 3rd 2018, Posted by: Drug Repurposing Portal

Scientists at the University of Dundee have shown that metformin, a routinely used drug for type 2 diabetes treatment, could help millions of patients with heart and circulatory diseases. Metformin could reverse the harmful thickening of the left ventricle in the heart, and could also successfulyl bring down high blood pressure, and reduce body weight in heart attack patients. Further-more, metformin was found to be helpful in patients with aortic stenosis and left ventricular hypertrophy by reducing insulin resistance and inflammation, which in turn could eventually reduce the size of the left ventricle.


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Anti-inflammatory properties of cannabidiol in Experimental Allergic Contact Dermatitis

June 3rd 2018, Posted by: Drug Repurposing Portal

Cannabidiol, a recently approved drug for Lennox-Gastaut epilepsy, also shows anti-inflammatory properties in an experimental model of atopic contact dermatitis. Phytocannabinoids modulate inflammatory responses by regulating the production of cytokines in several experimental models of inflammation. Cannabinoid type-2 (CB2) receptor activation was shown to reduce the production of the monocyte chemotactic protein-2 (MCP-2) chemokine in polyinosinic-polycytidylic acid [poly-(I:C)]-stimulated human keratinocyte (HaCaT) cells, an in vitro model of allergic contact dermatitis (ACD).


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Rare disease clinical trials trends: plotting strategies to address rare disease drug development

June 3rd 2018, Posted by: Drug Repurposing Portal

Rare diseases are also known as orphan diseases because pharma companies are generally not interested in addressing them. It is challenging to develop drugs for rare diseases because very few patients suffer from such diseases, making it difficult to obtain relevant data. The present study compared and analysed clinical trials data from three international registries, ClinicalTrials.gov (NCT), EU Clinical Trials Register (EUCTR), and the Japan Primary Registries Network (JPRN). This analysis is used to assess a trend of rare disease drug development so far, and to plot new strategies such as drug repositioning to tackle them.


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Repurposing drugs to treat l-DOPA-induced dyskinesia in Parkinson's disease

June 1st 2018, Posted by: Drug Repurposing Portal

The article describes the opportunity to repurpose drugs against l-DOPA-induced dyskinesia (LID) in Parkinson's disease, as it is one of the most suitable indication for exploring such an approach due to the abundance of data associated with it. The study discusses developmental strategies with the use of computational and artificial intelligence (AI)-driven platforms that might progress a candidate towards a Phase II clinical PoC. It also highlights a case study for the same by using the IBM Watson platform, where a training set of compounds with demonstrated ability to reduce LID, was employed to identify novel repurposing candidates. This led to the identification of several diverse candidates for repurposing in LID, originally envisaged for other indications, and which were already evaluated for their efficacy in non-human primate models of LID and/or clinically.


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Muscle relaxant Dantrolene could be repurposed to potentiate anti-sense mediated DMD exon skipping

May 31st 2018, Posted by: Drug Repurposing Portal

Duchenne muscular dystrophy (DMD) is a genetic disease caused by mutations which result in loss of dystrophin, a protein essential for muscle health. One way of avoiding transcription of the mutated gene is exon skipping, where presence of anti-sense oligonucleotide (AON) leads to exclusion of mutated exon, thus rescuing the partially functional dystrophin protein. This study proposes use of dantrolene, an approved muscle relaxant, as a skip booster to enhance AON-mediated rescue of partially functional dystrophin protein in mdx dystrophic mice.


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Anti-fungal drug itraconazole inhibits tumour re-growth in bowel cancer

May 31st 2018, Posted by: Drug Repurposing Portal

A recent study on mice demonstrated that itraconazole, an anti-fungal medication commonly prescribed for toenail infections, could effectively hals the growth and progression of certain types of bowel cancer. Itraconazole blocked signals from the Wnt pathway which is commonly implicated in the dissemination of several cancers. Blocking Wnt signaling could thus promote drug-induced senescence in dormant and non-dormant bowel cancer cells, and inhibit tumour re-growth.


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Computational functional genomics-based approaches in analgesic drug discovery and repurposing

May 28th 2018, Posted by: Drug Repurposing Portal

Persistent pain is a major global healthcare problem but with still limited treatment options. The present study highlights the use of computational functional genomics to analgesic drug discovery and repurposing. Functional genomics combines data derived from various processes related to DNA sequence, gene expression or protein function and uses advanced methods of data mining and knowledge discovery with the goal of understanding the relationship between the genome and the phenotype. In order to achieve this, authors have demonstrated a workflow using a novel R library 'dbtORA'.


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Repurposing anti-tapeworm drug Niclosamide for Renal Cell Carcinoma

May 23rd 2018, Posted by: Drug Repurposing Portal

A new study investigated anti-cancer functions of FDA approved anti-helminthic drug Niclosamide in renal cell carcinoma (RCC). Niclosamide induced apoptosis and effectively inhibited proliferation, migration, and cell cycle progression in human renal cancer cells both in vitro as well as in vivo. Interestingly, Niclosamide enhanced anti-cancer activity of Sorafenib in suppressing RCC cell proliferation. Together these findings suggest that Niclosamide is a potential addition to the treatment armamentarium for RCC alone, or in combination with other anti-cancer drugs.


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New applications for cannabinoids in glioblastoma therapy

May 16th 2018, Posted by: Drug Repurposing Portal

Cannabinoids are proposed to have potent anti-tumor functions, and could be potentially used to treat one of the deadliest types of cancer, the glioblastomas. This study summarises latest pre-clinical and clinical findings on molecular effects of cannabinoids to treat glioblastomas.


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Drug repositioning for effective prostate cancer treatment through identification of drugs with tolerable adverse effects

May 14th 2018, Posted by: Drug Repurposing Portal

Chemotherapeutic agents are notorious for severe adverse events. This study uses drug repositioning to identify non-cancer drugs which have anti-cancer activity as well as tolerable adverse effects to treat prostate cancer. 25 repurposed drug candidates covering diverse mechanisms such as inhibition of mTOR and VEGFR2 signaling, inhibition of PI3K/Akt signaling, COX and selective COX-2 inhibition, NF-κB inhibition, Wnt/β-Catenin pathway inhibition, DNMT1 inhibition, and GSK-3β inhibition were identified in this context. Also, the study explored combination therapy with current anti-cancer drugs as a means to increase drug efficiency and reduce adverse events.


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Potential new cure found for baldness

May 8th 2018, Posted by: Drug Repurposing Portal

A potential new cure for baldness has been discovered using a drug originally intended to treat osteoporosis. Enhanced hair growth is a side-effect of cyclosporine A, used to treat autoimmune diseases. Cyclosporine A also inhibited SFRP1, that blocks a molecular pathway, WNT, vital for the growth of many tissues, including hair. The new drug, Way-316606, that was designed to inhibit SFRP1 as treatment for osteoporosis has also shown promise with samples containing scalp hair follicles from more than 40 male hair-transplant patients.


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PregOMICS-Leveraging systems biology and bioinformatics for drug repurposing in maternal-child health.

May 4th 2018, Posted by: Drug Repurposing Portal

We describe the techniques and steps used in the use of 'omics data for drug repurposing.


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An extensive literature search approach for repurposing drugs for glioblastoma

May 2nd 2018, Posted by: Drug Repurposing Portal

Glioblastoma multiforme is the most common, aggressive and lethal type of brain tumour. The approach to treat glioblastoma has not suffered major changes over the last decade and temozolomide (TMZ) remains the mainstay for chemotherapy. The lack of effective options is a reality that may be counterbalanced by repositioning known and commonly used drugs for other diseases. This approach takes into consideration the available pharmacokinetic, pharmacodynamic, toxicity and safety data, and allows a much faster and less expensive drug and product development process.


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Could this common diabetes drug prevent cocaine relapse?

May 1st 2018, Posted by: Drug Repurposing Portal

A recent study published in Neuropsychopharmacology suggests that drugs already approved to treat obesity and type 2 diabetes might also help to treat cocaine addiction by reducing relapse. Exendin-4 mimics a hormone that reduces blood sugar and food consumption and is approved for the treatment of type 2 diabetes and obesity. The study reported a decrease cocaine-seeking behavior in addicted rats during withdrawal.


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Repurposing rosiglitazone, a PPAR-γagonist and oral antidiabetic, as an inhaled formulation, for the treatment of PAH.

April 30th 2018, Posted by: Drug Repurposing Portal

The role of PPAR-γ has been implicated in the pathogenesis of pulmonary hypertension (PAH). A PPAR-γ agonist, rosiglitazone used as an oral antidiabetic, has shown promise as an inhaled formulation, for the treatment of PAH. Rosiglitazone ameliorates the pathogenesis of PAH by balancing the molecular regulators involved in the vasoconstriction and vasodilation of human pulmonary arterial smooth muscle cells.


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Clustering based drug-drug interaction networks for possible repositioning of drugs

April 27th 2018, Posted by: Drug Repurposing Portal

A novel approach of analyzing drug-drug interaction networks, based on clustering methodology is used to reposition effective compounds against mutant EGFR having G719X, exon 19 deletions/insertions, L858R, and L861Q mutations.


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Repurposing existing drugs reveals molecules that control body clocks

April 19th 2018, Posted by: Drug Repurposing Portal

High-throughput chemical screening of over 1000 compounds consisting of approved drugs from USA, Europe, and Asia identified 13 circadian period-shortening compounds by a joint research collaboration between researchers at ITbM, National Institute for Basic Biology, Kyoto Prefectural University of Medicine, and Kindai University. Repurposing researchers focused on a steroid hormone, dehydroepiandrosterone (DHEA), which is commercially available as an anti-aging supplement in USA. Using drug repurposing, Yoshimura's group not only identified circadian rhythm changing drugs, but also succeeded in identifying genes that are involved in the regulation of the circadian clock.


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Aptar Pharma Discusses The Benefits Of Drug Repurposing In April

April 19th 2018, Posted by: Drug Repurposing Portal

Aptar Pharma featured in ONdrugDelivery magazine of April edition entitled 'Drug Repurposing - Broadening Patient Accessibility Via a Change in Drug Delivery System', focuses on the advantages of drug repurposing especially in nasal drug delivery systems spanning a wide range of routes of administration including nasal, pulmonary, ophthalmic, dermal and injectable. Their focus is on the nasal drug delivery system which offers varied range of benefits to the patients in terms of convenience, ease of administration and efficacy.


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The repurposing of ivermectin for malaria

April 2nd 2018, Posted by: Drug Repurposing Portal

This study developed and validated an ivermectin physiologically-based pharmacokinetic model in healthy adults and paediatric subjects and in a representative adult malaria population group (Thailand).


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Martin Pharmaceuticals Receives FDA Orphan Drug Designation for LIVANTRA

March 30th 2018, Posted by: Drug Repurposing Portal

Martin Pharmaceuticals, a clinical stage pharmaceutical company focused on repurposing already-approved drugs to offer life-changing advances to patients afflicted with rare (orphan) diseases or challenging medical conditions, has been granted Orphan Drug Designation by the U.S. Food & Drug Administration (FDA) for LIVANTRA in the treatment of Acute on Chronic Liver Failure.


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Anticancer Agent LENVIMA (lenvatinib mesylate) Approved for Additional Indication of Unresectable Hepatocellular Carcinoma

March 30th 2018, Posted by: Drug Repurposing Portal

LENVIMA, used to treat certain types of thyroid cancers has been approved in Japan for unresectable hepatocellular carcinoma (HCC).This approval was based on a phase 3 clinical study (Study 304/REFLECT study) conducted by Eisai investigating LENVIMA as a first-line treatment in patients with unresectable HCC.


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Findings From Comprehensive Drug Repurposing Screening To Treat Epileptic Encephalopathy Published In Epilepsia

March 28th 2018, Posted by: Drug Repurposing Portal

Pairnomix, LLC published the results from a comprehensive drug repurposing screen performed for a patient with SCN8A epileptic encephalopathy in Epilepsia using a high-throughput screen of generic & marketed drugs and identified 90 drugs with therapeutic benefit against excess sodium influx in in vitro cell models.


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Parasite Drug Shows Effectiveness Against Mesothelioma

March 23rd 2018, Posted by: Drug Repurposing Portal

Dr. Antonio Giordano believes his team has cleared the path to the next breakthrough in the treatment of malignant pleural mesothelioma. The advancement involves a new use for an old drug, pyrvinium pamoate, which doctors have successfully used for more than 50 years to treat infections of pinworm parasite. This drug that no one expected to be involved with mesothelioma is potentially a new weapon against this aggressive type of tumor, Giordano told Asbestos.com. Our findings are exciting, very exciting. This one can move forward.


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Identification of small-molecule inhibitors of human Golgi mannosidase via a drug repositioning screen

March 23rd 2018, Posted by: Drug Repurposing Portal

Golgi mannosidases (GM) inhibitor-based therapies have gained significant attention for cancer treatment since they regulate several biological events such as cell-cell communication, differentiation, and apoptosis in cancer cells. However, no GM inhibitor has been approved or is in clinical development for anti-cancer treatment till date. A new study by researchers from Nihon University in Japan performed a drug repositioning screen of a compound and approved drugs library, and found that the estrogen receptor antagonists tamoxifen and raloxifene inhibited human GMs at the cellular level. They also found that the NSAID Sulindac could inhibit GMs.The study thus highlights the importance of drug repositioning and drug screening strategies for identifying new lead compounds for anti-cancer treatment.


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Combination of pyrvinium and paclitaxel could be potential treatment strategy for Renal Cell Carcinoma

March 23rd 2018, Posted by: Drug Repurposing Portal

This study evaluated anti-cancer functions of FDA approved anti-helminthic drug pyrvinium in clear cell renal cell carcinoma (RCC). Pyrvinium inhibited the growth and induced apoptosis in various RCC cell lines. In line, pyrvinium treatment decreased tumor growth and ?-catenin levels clear cell RCC xenograft mouse model. Additionally, combination of pyrvinium and paclitaxel resulted in greater efficacy in in vitro and in vivo. These findings suggest that pyrvinium is a potential addition to the treatment armamentarium for clear cell RCC


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Diabetes Medicine Reduces Liver Fat in Nonalcoholic Fatty Liver Disease

March 22nd 2018, Posted by: Drug Repurposing Portal

In people with type 2 diabetes, nonalcoholic fatty liver disease (NAFLD) is common and can progress to a severe liver disease known as nonalcoholic steatohepatitis (NASH). Now a study has found that empagliflozin, a newer treatment for type 2 diabetes, reduces liver fat in patients with NAFLD and diabetes.


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he prescribable drugs with efficacy in experimental epilepsies (PDE3) database for drug repurposing research in epilepsy

March 20th 2018, Posted by: Drug Repurposing Portal

This study aim was to create a database of ?prescribable? drugs, approved for other conditions, with published evidence of efficacy in animal models of epilepsy, and to collate data that would assist in choosing the most promising candidates for drug repurposing. The database was created by the following: (1) computational literature?mining using novel software that identifies Medline abstracts containing the name of a prescribable drug, a rodent model of epilepsy, and a phrase indicating seizure reduction; then (2) crowdsourced manual curation of the identified abstracts.The final database includes 173 drugs and 500 abstracts. It is made freely available at www.liverpool.ac.uk/D3RE/PDE3. The database is reliable: 94% of the included drugs have corroborative evidence of efficacy in animal models (for example, evidence from multiple independent studies).


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Quinacrine, an Anti-protozoan Drug, is a plausible drug candidate for p53-negative malignancies

March 19th 2018, Posted by: Drug Repurposing Portal

Quinacrine an approved drug with several medical applications. It is commonly used as an antiprotozoal, anthelmintic and in the treatment of giardiasis. Recent studies reported anti-tumor effects of Quinacrine through suppression of NF-?B and activation of p53. In line, the present study demonstrated the anti-cancer effect of Quinacrine via a novel pathway through the elimination of check point kinase 1/2 (Chk1/2) under p53 inactivated conditions both in vitro and in vivo suggesting the potential of Quinacrine repurposing for relapsed cancers, small-cell lung cancer, breast cancer as well as various p53-inactivated human malignancies.


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Simvastatin therapy for drug repositioning to reduce the risk of prostate cancer mortality in patients with hyperlipidemia

March 17th 2018, Posted by: Drug Repurposing Portal

Prostate cancer (PCa) is one of the most commonly diagnosed cancers in the western world, and the mortality rate from PCa in Asia has been increasing recently. Statins are potent inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase and are commonly used for treating hyperlipidemia, with beneficial effects for cardiovascular disease and they also exhibit anti-cancer activity. However, the protective effects of statins against PCa are controversial. In this study, we investigated the effect of two types of statins (simvastatin and lovastatin) and the mortality rate of PCa patients by using the Taiwan National Health Insurance Research Database (NHIRD). A total of 15,264 PCa patients with hyperlipidemia records and medical claims from the Registry of Catastrophic Illness were enrolled. The patients were divided into two cohorts based on their statin use before the diagnosis of PCa: statin users (n = 1,827) and non-statin users (n = 1,826).


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The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug

March 17th 2018, Posted by: Drug Repurposing Portal

Drug repositioning is a highly studied alternative strategy to discover and develop anticancer drugs. This drug development approach identifies new indications for existing compounds. Ivermectin belongs to the group of avermectins (AVM), a series of 16-membered macrocyclic lactone compounds discovered in 1967, and FDA-approved for human use in 1987. It has been used by millions of people around the world exhibiting a wide margin of clinical safety. In this review, we summarize the in vitro and in vivo evidences demonstrating that ivermectin exerts antitumor effects in different types of cancer. Ivermectin interacts with several targets including the multidrug resistance protein (MDR), the Akt/mTOR and WNT-TCF pathways, the purinergic receptors, PAK-1 protein, certain cancer-related epigenetic deregulators such as SIN3A and SIN3B, RNA helicase, chloride channel receptors and preferentially target cancer stem-cell like population. Importantly, the in vitro and in vivo antitumor activities of ivermectin are achieved at concentrations that can be clinically reachable based on the human pharmacokinetic studies done in healthy and parasited patients. Thus, existing information on ivermectin could allow its rapid move into clinical trials for cancer patients.


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Repurposing of Kinase Inhibitors as Broad-Spectrum Antiviral Drugs

March 16th 2018, Posted by: Drug Repurposing Portal

There is an urgent need for antiviral strategies to combat hundreds of human disease-causing viruses. Currently approved antiviral drugs treat fewer than ten viral infections. A majority of these drugs are direct-acting antivirals (DAAs) that target proteins encoded by individual viruses. As such, this approach provides a narrow spectrum of coverage and therefore cannot address the large clinical need. Targeting host proteins required by multiple viruses can thus provide a broad-spectrum coverage with a possible added benefit of a high genetic barrier to resistance. Moreover, a broad-spectrum therapeutic could be administered even before a viral threat has been accurately diagnosed, thereby increasing protection. Host kinase inhibitors represent one category of compounds with a great potential to be repurposed as broad-spectrum antivirals. Viruses hijack a large number of host kinases at distinct steps of their life cycle (Supekova et al., 2008; Li et al., 2009; Keating a nd Striker, 2012; Jiang et al., 2014). Some of these host kinases are broadly required and thus represent attractive targets for broad-spectrum therapy. These findings, combined with the development and approval of a large number of kinase inhibitors for the treatment of cancer (Gross et al., 2015) and inflammatory conditions (Ott and Adams, 2011) have sparked efforts aimed to determine the therapeutic potential of such drugs to combat viral infections.


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Repurposed arthritis drug could become a non-opioid pain reliever

March 16th 2018, Posted by: Drug Repurposing Portal

Researchers from the Indiana University in the US have found that the CB2 cannabinoid receptor agonist LY2828360, once studied as a possible treatment option for osteoarthritis, might have the potential to be used as a non-opioid pain reliever. In the study performed on mice, the researchers observed that when combined with morphine, the cannabinoid agonist was able to block chemotherapy-induced neuropathic pain with sustained efficacy, and concomitantly attenuated tolerance and dependence towards morphine. Thus, LY2828360 could be repurposed to serve as a first-line treatment in chemotherapy-induced neuropathic pain, and also hold therapeutic promise in other opioid analgesic-refractory neuropathic pains.


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Chondroprotective Effects and Mechanisms of Dextromethorphan: Repurposing Antitussive Medication for Osteoarthritis Treatment.

March 16th 2018, Posted by: Drug Repurposing Portal

Dextromethorphan (DXM), an antitussive medication has been found to be protective in pro-inflammatory cytokine-stimulated chondrocytes and in a collagen-induced arthritis (CIA) animal model. DXM protected the CIA mice from severe inflammation and cartilage destruction by reducing the inflammation-mediated matrix degradation.


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An ancient remedial repurposing: synthesis of new pinocembrin fatty acid acyl derivatives as potential antimicrobial/anti-inflammatory agents

March 16th 2018, Posted by: Drug Repurposing Portal

Five new pinocembrin derivatives (MC1-MC5) synthesized by Steglich reaction were investigated for their antimicrobial, antioxidant, and anti-inflammatory activity in this study. MC2 (oleoyl derivative) and MC3 (linoleoyl derivative) have shown the highest inhibitory effects on bacterial proliferation against Staphylococcus aureus. The docosahexaenoyl derivative MC5 displays the highest anti-inflammatory activity, decreasing nitric oxide production in LPS-stimulated. The introduction of fatty acid substituents improves the biological profile of pinocembrin. Moreover, the chemical nature of substituents significantly affects the bioactivity. These preliminary results outline the importance to investigate the synthesis of pinocembrin fatty acids derivatives as new and safe anti-microbial/anti-inflammatory agents.


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DNA methylation-based classification of central nervous system tumours

March 15th 2018, Posted by: Drug Repurposing Portal

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging with substantial inter-observer variability in the histopathological diagnosis of many tumour types. In the article the authors report a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. They demostrate that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. The results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.


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Inventing new therapies without reinventing the wheel: the power of drug repurposing

March 15th 2018, Posted by: Drug Repurposing Portal

Current drug development strategies devote extensive effort to identifying the molecular mechanism of action of new drug candidates. Often, if more than one unrelated enzyme or protein is affected by a certain agent at similar concentrations, the agent is considered to be ?non-specific? (or not specific enough) and thus of questionable therapeutic utility. However, specificity for drugs is surprisingly not only a function of concentration, as thought in pharmacology books, but also a function of time: the more a drug is studied, the more likely it is that additional targets or indications will be discovered. In 1993, the Nobel Laureate Sir John Vane ? who spent his career studying drugs and their modes of action ? said that ?The specificity of drugs decreases over time? (Sir John Vane ? while making this comment to a group of young investigators including one of the authors of this Editorial (C.S.) ? also stated that he believes that this quote originally belongs to another prominent pharmacologist, Sir James Black (also a Nobel Laureate). In spite of extensive internet searches, we were unable to verify the origin of the original quote.). On the one hand, additional targets might mean trouble for a drug candidate under development. On the other hand, new molecular targets and new pharmacological actions may present new therapeutic opportunities for clinically used drugs ? in the framework of therapeutic repurposing.


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A diseasome cluster-based drug repurposing of soluble guanylate cyclase activators from smooth muscle relaxation to direct neuroprotection

March 15th 2018, Posted by: Drug Repurposing Portal

Network medicine utilizes common genetic origins, markers and co-morbidities to uncover mechanistic links between diseases. These links can be summarized in the diseasome, a comprehensive network of disease?disease relationships and clusters. The diseasome has been influential during the past decade, although most of its links are not followed up experimentally. Here, the authors' team investigate a high prevalence unmet medical need cluster of disease phenotypes linked to cyclic GMP. Hitherto, the central cGMP-forming enzyme, soluble guanylate cyclase (sGC), has been targeted pharmacologically exclusively for smooth muscle modulation in cardiology and pulmonology. Here, we examine the disease associations of sGC in a non-hypothesis based manner in order to identify possibly previously unrecognized clinical indications. Surprisingly, they found that sGC, is closest linked to neurological disorders, an application that has so far not been explored clinically. Indeed, when investigating the neurological indication of this cluster with the highest unmet medical need, ischemic stroke, pre-clinically they found that sGC activity is virtually absent post-stroke. Conversely, a heme-free form of sGC, apo-sGC, was now the predominant isoform suggesting it may be a mechanism-based target in stroke. Indeed, this repurposing hypothesis could be validated experimentally in vivo as specific activators of apo-sGC were directly neuroprotective, reduced infarct size and increased survival. Thus, common mechanism clusters of the diseasome allow direct drug repurposing across previously unrelated disease phenotypes redefining them in a mechanism-based manner. Specifically, our example of repurposing apo-sGC activators for ischemic stroke should be urgently validated clinically as a possible first-in-class neuroprotective therapy.


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High-throughput screen of drug repurposing library identifies inhibitors of Sarcocystis neurona growth

March 15th 2018, Posted by: Drug Repurposing Portal

The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM), a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are 60?70% effective. Advancement of treatment requires new technology to identify new drugs for EPM. To address this critical need, the researchers developed, validated, and implemented a high-throughput screen to test 725 FDA-approved compounds from the NIH clinical collections library for anti-S. neurona activity. Their screen identified 18 compounds with confirmed inhibitory activity against S. neurona growth, including compounds active in the nM concentration range. Many identified inhibitory compounds have well-defined mechanisms of action, making them useful tools to study parasite biology in addition to being potential therapeutic agents. In comparing the activity of inhibitory compounds identified by their screen to that of other screens against other apicomplexan parasites, we found that most compounds (15/18; 83%) have activity against one or more related apicomplexans. Interestingly, nearly half (44%; 8/18) of the inhibitory compounds have reported activity against dopamine receptors. They also found that dantrolene, a compound already formulated for horses with a peak plasma concentration of 37.8???12.8?ng/ml after 500?mg dose, inhibits S. neurona parasites at low concentrations (0.065??M [0.036?0.12; 95% CI] or 21.9?ng/ml [12.1?40.3; 95% CI]). These studies demonstrate the use of a new tool for discovering new chemotherapeutic agents for EPM and potentially providing new reagents to elucidate biologic pathways required for successful S. neurona infection.


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Use of Computational Functional Genomics in Drug Discovery and Repurposing for Analgesic Indications

March 15th 2018, Posted by: Drug Repurposing Portal

The novel research area of functional genomics investigates biochemical, cellular, or physiological properties of gene products with the goal of understanding the relationship between the genome and the phenotype. These developments have made analgesic drug research a data-rich discipline mastered only by making use of parallel developments in computer science, including the establishment of knowledge bases, mining methods for big data, machine-learning, and artificial intelligence.


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A novel computational approach for drug repurposing using systems biology

March 15th 2018, Posted by: Drug Repurposing Portal

Identification of novel therapeutic effects for existing U.S. Food and Drug Administration (FDA)-approved drugs, drug repurposing, is an approach aimed to dramatically shorten the drug discovery process, which is costly, slow and risky. Several computational approaches use transcriptional data to find potential repurposing candidates. The main hypothesis of such approaches is that if gene expression signature of a particular drug is opposite to the gene expression signature of a disease, that drug may have a potential therapeutic effect on the disease. However, this may not be optimal since it fails to consider the different roles of genes and their dependencies at the system level.


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Drug repurposing: In-vitro anti-glycation properties of 18 common drugs

March 15th 2018, Posted by: Drug Repurposing Portal

Article Authors Metrics Comments Related Content Abstract Introduction Materials and methods Results and discussion Conclusion Supporting information Acknowledgments References Reader Comments (0) Media Coverage (0) Figures Abstract Drug repositioning or repurposing, i.e. identifying new indications for existing drugs, has gained increasing attention in the recent years. This approach enables the scientists to discover ?new targets? for known drugs in a cost and time efficient manner. Glycation, the non-enzymatic reaction of sugars with proteins or nucleic acids to form early glycation (Amadori or fructosamine) products, is a key molecular basis of diabetic complications. Inhibiting the process of non-enzymatic protein glycation is one of the key strategies to prevent glycation-mediated diabetic complications. The present study focuses on the anti-glycation activity of 18 drugs, commonly used for the treatment of gastrointestinal, central nervous system, inflammatory diseases, bacterial infections, and gout.


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Ibandronate metal complexes: solution behavior and antiparasitic activity

March 14th 2018, Posted by: Drug Repurposing Portal

Bisphosphonates that are clinically used for bone diseases have been studied as agents against Trypanosoma cruzi, causative parasite of Chagas disease.


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Chemotherapeutic potential of 17-AAG against cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis.

March 14th 2018, Posted by: Drug Repurposing Portal

Previously, we showed that 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), a Heat Shock Protein 90 (HSP90)-specific inhibitor, reduces L. (L.) amazonensis infection in vitro. Herein, we expand the current knowledge on the leishmanicidal activity of 17-AAG against cutaneous leishmaniasis, employing an experimental model of infection with L. (V.) braziliensis.


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The existing drug vorinostat as a new lead against cryptosporidiosis by targeting the parasite histone deacetylases.

March 14th 2018, Posted by: Drug Repurposing Portal

Fifteen (15) compounds exhibited anti-cryptosporidial activity at nanomolar level in vitro. Among them, the histone deacetylase (HDAC) inhibitor vorinostat retained outstanding efficacy in vitro (EC50 = 203 nM) and in IL-12 knockout mouse model (ID50 = 7.5 mg/kg). Vorinostat was effective on various parasite developmental stages, and could irreversibly kill the parasite. Vorinostat was highly effective against the parasite native HDAC enzymes (IC50 = 90.0 nM) and a recombinant C. parvum HDAC (Ki = 123.0 nM).


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Repurposed Leukemia Drugs Could Ward Off Melanoma Metastasis

March 14th 2018, Posted by: Drug Repurposing Portal

Study published in Science Signaling has showed new evidence linking the activation of ABL kinases - cancer-promoting genes - to the secretion of pro-metastatic cathepsins in melanoma. The Cathepsins are enzymes that degrade proteins and are highly expressed in cancer cells, resulting in their release into the environment between the cells. These enzymes "chew up" the fibrous matrix around tumors, which allows them to get into the blood stream and lymphatic system and spread around the body. Their work showed that ABL kinases induce cathepsin expression and secretion by increasing the activity of key transcription factors that upregulate numerous proteins involved in metastasis. Transcription factors bind to the regulatory part of genes and induce their expression. This study is the first to demonstrate that ABL kinases not only increase the abundance of the transcription factors, but also regulate the ability of these transcription factors to bind to the promoters and induce gene expression. The researchers found that ABL kinases inhibitors already approved by the Food & Drug Administration (FDA) for treating leukemia also prevented metastasis induced by secreted cathepsins in animal models of metastatic melanoma


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Autism: Anti-cancer drug may improve social behavior

March 14th 2018, Posted by: Drug Repurposing Portal

Investigators at the State University of New York at Buffalo reveal that Romidepsin an anti-cancer drug may be able to reverse social impairments associated with autism.


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FoxO3a mediates the inhibitory effects of the antiepileptic drug Lamotrigine on breast cancer growth

March 14th 2018, Posted by: Drug Repurposing Portal

Researchers at the University of Calabria show that Lamotrigine (LTG), a broadly used anticonvulsivant, could be "repurposed" as an antitumoral drug in Breast Cancer. They show that LTG inhibits the proliferation, the anchorage-dependent and independent cell growth in BC cells (BCCs), including hormone-resistant cell models.


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Repositioning an orphan chemical library by inverse virtual screening.

March 12th 2018, Posted by: Drug Repurposing Portal

Inverse Virtual Screening (IVS) is a docking based approach aimed to the evaluation of the virtual ability of a single compound to interact with a library of proteins. For the first time, we applied this methodology to a library of synthetic compounds, which proved to be inactive towards the target they were initially designed for.


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Using a novel computational drug-repositioning approach (DrugPredict) to rapidly identify potent drug candidates for cancer treatment

March 9th 2018, Posted by: Drug Repurposing Portal

Computation-based drug-repurposing/repositioning approaches can greatly speed up the traditional drug discovery process. To date, systematic and comprehensive computation-based approaches to identify and validate drug-repositioning candidates for epithelial ovarian cancer (EOC) have not been undertaken. Here, we present a novel drug discovery strategy that combines a computational drug-repositioning system (DrugPredict) with biological testing in cell lines in order to rapidly identify novel drug candidates for EOC.


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Computational drug repositioning using low-rank matrix approximation and randomized algorithms

March 9th 2018, Posted by: Drug Repurposing Portal

Computational drug repositioning is an important and efficient approach towards identifying novel treatments for diseases in drug discovery. The emergence of large-scale, heterogeneous biological and biomedical datasets has provided an unprecedented opportunity for developing computational drug repositioning methods. The drug repositioning problem can be modeled as a recommendation system that recommends novel treatments based on known drug?disease associations. The formulation under this recommendation system is matrix completion, assuming that the hidden factors contributing to drug?disease associations are highly correlated and thus the corresponding data matrix is low-rank.


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Indian scientists find asthma drug to be useful against tuberculosis as well

March 9th 2018, Posted by: Drug Repurposing Portal

Scientists at the Indian Institute of Science in Bangalore have found that an existing anti-asthma drug is effective against tuberculosis and can help address the problem of drug resistance as well. The drug targets a unique arginine biosynthesis enzyme which is exclusive to Mtb, thereby impeding its arginine production. It also targets the pathogen pro-survival pathways in the host, directly reducing intracellular survival of the TB bacteria.


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Repurposed Parasite Drug New Weapon Against Mesothelioma

March 9th 2018, Posted by: Drug Repurposing Portal

Anthelmintic drug pyrvinium pamoate, already approved to treat infections of pinworm parasite was shown to effectively impair both mesothelioma cell growth and migration. Researchers found that the drug affected the expression of downstream genes in the WNT signaling pathway, which are implicated in mesothelioma aggressiveness and its resistance to conventional therapy.


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gene2drug: a computational tool for pathway-based rational drug repositioning

February 26th 2018, Posted by: Drug Repurposing Portal

Drug repositioning has been proposed as an effective shortcut to drug discovery. The availability of large collections of transcriptional responses to drugs enables computational approaches to drug repositioning directly based on measured molecular effects. We introduce a novel computational methodology for rational drug repositioning, which exploits the transcriptional responses following treatment with small molecule. Specifically, given a therapeutic target gene, a prioritisation of potential effective drugs is obtained by assessing their impact on the transcription of genes in the pathway(s) including the target. We performed in silico validation and comparison with a state-of-art technique based on similar principles.


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Repurposing probenecid for the Treatment of Heart Failure

February 23rd 2018, Posted by: Drug Repurposing Portal

Probenecid, an FDA approved drug for the treatment of gout and hyperuricemia is recently been in phase II clinical trials for the treatment of heart failure. In their recent study, Robbins and coworkers revealed that probenecid increased the calcium sensitivity of cardiomyocytes likely through the stimulation of cardiac TRPV2 channels. In line, probenecid also improved the heart-pumping function in heart failure patients with reduced ejection fraction


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Repurposed Drug Hydroxyurea May Improve Glioblastoma's Response to Chemotherapy

January 24th 2018, Posted by: Drug Repurposing Portal

Glioblastoma (GBM) is the most common and most aggressive type of brain tumors in adults. Over the last two decades, the major improvement in the treatment for GBM has been the addition of the chemotherapeutic temozolomide (TMZ) to the standard of care (surgery and radiation), however, despite this aggressive therapy, over 90% of patients die within five years after diagnosis. Combining FDA-approved drug hydroxyurea with TMZ for the treatment of GBM could be highly beneficial for these patients, which could lead to an increase in their survival rate.


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One gene links two different diseases: A stretch of DNA is implicated in both Crohn's and Parkinson's diseases

January 24th 2018, Posted by: Drug Repurposing Portal

Inga Peter of the Icahn School of Medicine at Mount Sinai in New York City and her colleagues analysed gene sequences in more than 2,000 people with Crohn's disease and 3,600 individuals without the condition, all of whom were of Ashkenazi Jewish descent. The team found a link between Crohn's disease and a particular DNA sequence in a gene called LRRK2. The variant DNA causes the LRRK2 protein to become more active than the typical protein — as does a Parkinson's disease-associated variant in the same part of the protein.


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Anti-cryptosporidial activity of anti-neoplastic drug vorinostat

January 8th 2018, Posted by: Drug Repurposing Portal

Cryptosporidiosis is an intestinal disease caused by the microsopic parasite Cryptosporidium that can cause life-threatening disease in individuals with weak immune system. The existing therapeutic options for cryptosporidiosis are very limited and symptomatic. Recently published study exhibited anti-cryptosporidial activity of histone deacetylase (HDAC) inhibitor vorinostat at nanomolar level in vitro. The study also demonstrated irreversible killing of the parasite by vorinostat by inhibiting the parasite at different developmental stages via targeting parasite?s HDAC enzymes. These data suggest the potential for repurposing of vorinostat to treat cryptosporidiosis.


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Anti-cryptosporidial activity of anti-neoplastic drug vorinostat

January 8th 2018, Posted by: Drug Repurposing Portal

Cryptosporidiosis is an intestinal disease caused by the microsopic parasite Cryptosporidium that can cause life-threatening disease in individuals with weak immune system. The existing therapeutic options for cryptosporidiosis are very limited and symptomatic. Recently published study exhibited anti-cryptosporidial activity of histone deacetylase (HDAC) inhibitor vorinostat at nanomolar level in vitro. The study also demonstrated irreversible killing of the parasite by vorinostat by inhibiting the parasite at different developmental stages via targeting parasite’s HDAC enzymes. These data suggest the potential for repurposing of vorinostat to treat cryptosporidiosis.


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Novel diabetes drugs sensitize cancer cells to chemotherapy agents

January 4th 2018, Posted by: Drug Repurposing Portal

A recent study published in Proceedings of the National Academy of Sciences by scientists at the Dana-Farber Cancer Institute highlights the efficacy of experimental anti-diabetic drugs, similar to thiazolidinediones (TZDs), in sensitizing lung cancer cells to conventional chemotherapeutic agents such as carboplatin. This effect was also reproducible in triple-negative breast cancer cells, and resulted in their self-destruction. The molecular mechanism of action involved phosphorylation of PPAR-gamma, a receptor essential for fat cell development, and a target of the TZD class of anti-diabetic agents. Coincidentally, PPAR-gamma is dysregulated in various cancers such as lung, triple-negative breast, colorectal, and pancreatic cancers. Thus, repurposing diabetes drugs in combination with traditional chemotherapeutic agents for various malignancies could potentially improve clinical outcomes in cancer patients.


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Repurposing anticonvulsants for treatment of injury-induced osteoarthritis

January 4th 2018, Posted by: Drug Repurposing Portal

Drugs designed for the treatment of central nervous system diseases could also be used to prevent the development of injury-induced arthritis, potentially saving the NHS around half a billion pounds a year


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Diabetes Drug 'Significantly Reverses' Memory Loss in Mice with Alzheimer's

January 3rd 2018, Posted by: Drug Repurposing Portal

A drug developed for diabetes could be used to treat Alzheimer's after scientists found it "significantly reversed memory loss" in mice through a triple method of action.This is the first time that a triple receptor drug has been used which acts in multiple ways to protect the brain from degeneration. It combines GLP-1, GIP and Glucagon which are all growth factors.The study used APP/PS1 mice, which are transgenic mice that express human mutated genes that cause Alzheimer's. Those genes have been found in people who have a form of Alzheimer's that can be inherited. Aged transgenic mice in the advanced stages of neurodegeneration were treated.Although the benefits of these 'triple agonist' drugs have so far only been found in mice, other studies with existing diabetes drugs such as liraglutide have shown real promise for people with Alzheimer's, so further development of this work is crucial.


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Drug repurposing for the treatment of glioblastoma multiforme

January 3rd 2018, Posted by: Drug Repurposing Portal

Glioblastoma Multiforme is the deadliest type of brain tumor and is characterized by very poor prognosis with a limited overall survival. Current optimal therapeutic approach has essentially remained unchanged for more than a decade, consisting in maximal surgical resection followed by radiotherapy plus temozolomide.Needless to say, in order to efficiently repurpose drugs that are already approved for human use, a careful selection is required, followed by thorough demonstration of their effectiveness in other biological contexts. We will now discuss some methods useful for selection of effective testing and repurposing of drugs in cancer therapy.


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Drug Discovery Could Accelerate Hugely with Machine Learning

December 20th 2017, Posted by: Drug Repurposing Portal

The algorithm?partly devised by Dr. James Kermode from Warwick?s School of Engineering?can accurately predict the interactions between a protein and a drug molecule based on a handful of reference experiments or simulations.\nUsing just a few training references, it can predict whether or not a candidate drug molecule will bind to a target protein with 99 percent accuracy. The algorithm can also tackle materials-science problems such as modeling the subtle properties of silicon surfaces, and promises to revolutionize materials and chemical modeling?giving insight into the nature of intermolecular forces. The design of this algorithm, which combines local information from the neighborhood of each atom in a structure, makes it applicable across many different classes of chemical, materials science, and biochemical problems. The research illustrates how chemical and materials discovery is now benefitting from the Machine Learning and Artificial Intelligence approache s that already underlie technologies from self-driving cars to go-playing bots and automated medical diagnostics.\nNew algorithms allow us to predict the behavior of new materials and molecules with great accuracy and little computational effort, saving time and money in the process.


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Tapeworm Drug Could Lead the Fight Against Parkinson\'s Disease

December 19th 2017, Posted by: Drug Repurposing Portal

Researchers at Cardiff University, in collaboration with the University of Dundee, have identified a drug molecule (Niclosamide) used to treat tapeworm infections which could lead to new treatments for patients with Parkinson\'s disease.Several studies have suggested that discovering a drug which is capable of enhancing the function of PINK1 could be a significant step in halting neurodegeneration and therefore slow down or even treat Parkinson\'s disease.Researchers at Cardiff and Dundee Universities have discovered that is an effective activator of the PINK1 protein.Now these findings to the next level by evaluating the ability of Niclosamide to treat Parkinson\'s disease in disease models.


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Large-Scale Off-Target Identification Using Fast and Accurate Dual Regularized One-Class Collaborative Filtering and Its Application to Drug Repurposing

December 18th 2017, Posted by: Drug Repurposing Portal

Target-based screening is one of the major approaches in drug discovery. Besides the intended target, unexpected drug off-target interactions often occur, and many of them have not been recognized and characterized. The off-target interactions can be responsible for either therapeutic or side effects. Thus, identifying the genome-wide off-targets of lead compounds or existing drugs will be critical for designing effective and safe drugs, and providing new opportunities for drug repurposing. Although many computational methods have been developed to predict drug-target interactions, they are either less accurate than the one that we are proposing here or computationally too intensive, thereby limiting their capability for large-scale off-target identification. In addition, the performances of most machine learning based algorithms have been mainly evaluated to predict off-target interactions in the same gene family for hundreds of chemicals. It is not clear how these algor ithms perform in terms of detecting off-targets across gene families on a proteome scale. Here, we are presenting a fast and accurate off-target prediction method, REMAP, which is based on a dual regularized one-class collaborative filtering algorithm, to explore continuous chemical space, protein space, and their interactome on a large scale. When tested in a reliable, extensive, and cross-gene family benchmark, REMAP outperforms the state-of-the-art methods. Furthermore, REMAP is highly scalable. It can screen a dataset of 200 thousands chemicals against 20 thousands proteins within 2 hours. Using the reconstructed genome-wide target profile as the fingerprint of a chemical compound, we predicted that seven FDA-approved drugs can be repurposed as novel anti-cancer therapies. The anti-cancer activity of six of them is supported by experimental evidences. Thus, REMAP is a valuable addition to the existing in silico toolbox for drug target identification, drug repurposing, ph enotypic screening, and side effect prediction.


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Structure-based identification of a NEDD8-activating enzyme inhibitor via drug repurposing

December 18th 2017, Posted by: Drug Repurposing Portal

NEDD8-activating enzyme (NAE) is an important part of the NEDD8 conjugation pathway which regulates protein degradation. Meanwhile, drug repurposing is one such technique which is cost-efficient to identify new therapeutic uses for existing scaffolds. In this article, mitoxantrone (1) was repurposed as an inhibitor of NAE by virtual screening of an FDA-approved drug database. Compound 1 inhibited NAE activity in cell-free and cell-based systems with high selectivity and was competitive with ATP. Furthermore, compound 1 induced apoptosis of colorectal adenocarcinoma cancer cells through inhibiting the degradation of the neddylation substrate p53.


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Repurposing of the anti-malaria drug chloroquine for Zika Virus treatment and prophylaxis

December 18th 2017, Posted by: Drug Repurposing Portal

One of the major challenges of the current Zika virus (ZIKV) epidemic is to stop congenital foetal abnormalities, including microcephaly, following ZIKV infection of pregnant women. Given the urgent need for ZIKV prophylaxis and treatment, repurposing of approved drugs appears to be a viable and immediate solution. We demonstrate that the common anti-malaria drug chloroquine (CQ) increases the lifespan of ZIKV-infected interferon signalling-deficient AG129 mice. However, the severity of ZIKV infection in these mice precludes the study of foetal (vertical) viral transmission. Here, we show that interferon signalling-competent SJL mice support chronic ZIKV infection. Infected dams and sires are both able to transmit ZIKV to the offspring, making this an ideal model for in vivo validation of compounds shown to suppress ZIKV in cell culture. Administration of CQ to ZIKV-infected pregnant SJL mice during mid-late gestation significantly attenuated vertical transmission, reduci ng the ZIKV load in the foetal brain more than 20-fold. Given the limited side effects of CQ, its lack of contraindications in pregnant women, and its worldwide availability and low cost, we suggest that CQ could be considered for the treatment and prophylaxis of ZIKV.


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Repositioning CEP-1347, a chemical agent originally developed for the treatment of Parkinson's disease, as an anti-cancer stem cell drug.

December 15th 2017, Posted by: Drug Repurposing Portal

CEP-1347 is a promising candidate for cancer stem cell-targeting therapy. In vitro, CEP-1347 efficiently induced differentiation and inhibited the self-renewal and tumor-initiating capacities of human cancer stem cells from glioblastoma as well as from pancreatic and ovarian cancers at clinically-relevant concentrations, without impairing the viability of normal fibroblasts and neural stem cells. CEP-1347 is a mixed lineage kinase inhibitor tested in a large-scale phase 2/3 clinical trial in early Parkinson's disease.


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DrugPredict - a novel computational drug-repositioning approach to identify new drug candidates

December 15th 2017, Posted by: Drug Repurposing Portal

Researchers at the Case Western Reserve University have developed a new online drug repositioning, discovery and development tool that aids a user in browsing and in rapidly identifying a database of available FDA-approved small molecule drugs for new therapeutic applications. The system uses a predictive analysis approach to provide calculated probability values of the known mechanisms of action, clinical efficacy, and side effects of existing drugs in specific diseases. Applying the functionality of this tool to real-world issues, the researchers published their findings in Oncogene (PMID: 28967908) where they showed that common non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin were effective in eliminating patient-derived epithelial ovarian cancer cells. DrugPredict might hence be one among several drug repurposing tools that will aid in the quick identification of new medical uses of old drugs.


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Repurposing Drugs in Oncology (ReDO)-chloroquine and hydroxychloroquine as anti-cancer agents.

December 15th 2017, Posted by: Drug Repurposing Portal

Chloroquine (CQ) and hydroxychloroquine (HCQ) are well-known 4-aminoquinoline antimalarial agents. Scientific evidence also supports the use of CQ and HCQ in the treatment of cancer. Preclinical studies support CQ and HCQ use in anti-cancer therapy, especially in combination with conventional anti-cancer treatments since they are able to sensitize tumour cells to a variety of drugs, potentiating the therapeutic activity. Interestingly, CQ and HCQ exert effects both on cancer cells and on the tumour microenvironment.


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Structure-based identification of a NEDD8-activating enzyme inhibitor via drug repurposing.

December 15th 2017, Posted by: Drug Repurposing Portal

NEDD8-activating enzyme (NAE) is an essential player of the NEDD8 conjugation pathway that regulates protein degradation. Authors reported that Mitoxantrone was repurposed as an inhibitor of NAE by virtual screening of an FDA-approved drug database and inhibited NAE activity in cell-free and cell-based systems with high selectivity. Furthermore Mitoxantrone also induced apoptosis of colorectal adenocarcinoma cancer cells.


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Anti-parasite drug, nitazoxanide could be potential therapy for prostate cancer

December 14th 2017, Posted by: Drug Repurposing Portal

Researchers at the University of Bergen found anti-cancer activity of the parasitic drug nitazoxanide during multidrug screening. They demonstrated that nitazoxanide inhibited cancer cell growth by degradation of the protein beta-catenin. These data suggest for the possibility of repurposing the anti-parasite drug nitazoxanide for prostate cancer treatment.


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Antimalarial drug chloroquine could be repurposed to treat Zika virus infection

December 14th 2017, Posted by: Drug Repurposing Portal

Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) and UC San Diego School of Medicine during their investigations treated Zika infected pregnant mice with chloroquine and found that chloroquine markedly decreased the viral load in maternal blood and neural progenitor cells in the fetal brain. These data demonstrate a new use for the long standing drug chloroquine for targeting Zika virus infection.


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Anti-diabetic drug Metformin can reverse and prevent the onset of multi-drug resistance in breast cancer

December 14th 2017, Posted by: Drug Repurposing Portal

A new study published in PLOS One indicates that the diabetes wonder drug Metformin can potentially inhibit the development of multi-drug resistance (MDR) in the breast cancer cells. Recent clinical findings underscore the importance of the anti-proliferation effect of metformin in multiple cancer sub-types. The authors observed that pretreatment of MCF7 breast cancer cells with metformin prevented or delayed the development of drug resistance. Moreover, metformin was also found to reverse MDR-associated protein markers after the onset of drug resistance in aggressive breast cancer in mouse models. More research is required to assess the short- and long-term sustained effects of metformin in neoplastic cells.


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Researchers Show Aspirin Added to Cancer Drug Improves Effectiveness

December 14th 2017, Posted by: Drug Repurposing Portal

UQ Diamantina Institute researcher Associate Professor Helmut Schaider said cancers driven by mutations in a group of genes, known as RAS, had a low response to treatments with currently no drug directly targeting them. They found that the addition of aspirin to a cancer inhibitor drug, Sorafenib, strongly enhanced its effectiveness against mouse models of lung cancer and melanoma with RAS mutations.scientists are hoping clinical trials could soon be underway for people with lung, pancreatic and colorectal cancers that have not responded to other therapies.


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How cancer could be treated with an old alcoholism drug

December 14th 2017, Posted by: Drug Repurposing Portal

Previous studies have demonstrated that the alcohol abuse drug disulfiram has anticancer properties. But until now, researchers had not found the mechanism by which the drug can target cancer. New research sheds light, paving the way for the repurposing of the drug


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Copaxone, an old drug for Multiple Sclerosis, is an intriguing new therapeutic tool to fight antibiotic resistance

December 14th 2017, Posted by: Drug Repurposing Portal

Giving new life to old drugs is the need of the hour to fight several diseases and infections. One of the latest breakthroughs in the battle against superbugs comes in the form of Glatiramer Acetate or Copaxone, a drug used over two decades to treat Multiple Sclerosis. A team of researchers led by Thomas Vorup-Jensen from the department of biomedicine at Aarhus University, Denmark found copaxone to have huge potential in killing antibiotic-resistant gram negative bacteria within minutes.The study published in Nature highlights that the chemical properties of copaxone's proteins are highly similar to antimicrobial peptides, as a result of which, the drug easily eliminated the infectious gram negative bacteria E.coli and Pseudomonas Aeruginosa. The researchers studied this property of copaxone in patients with Cyctic Fibrosis, whose lungs cannot clear mucus due to infestation with Pseudomonas bacteria, and found remarkable therapeutic benefits. The study hence underscored that in the frantic fight against antibiotic-resistance, repurposing old drugs such as copaxone could help in finding cures for difficult-to-treat medical ailments.


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New-age cancer drug Nivolumab has the potential to eradicate HIV infections in patients

December 14th 2017, Posted by: Drug Repurposing Portal

Nivolumab (trade name Opdivo), a new generation drug used in the targeted therapy of cancers such as metastatic melanoma, squamous non-small cell lung cancer, and renal cell carcinoma could potentially treat millions of HIV-positive patients. According to the findings of a study in the Annals of Oncology on a 51 year old HIV-positive man being treated for lung cancer, it was found that nivolumab reduced the reservoir of latent HIV-infected cells and boosted the immunity in the patient by increasing the activity of CD8 killer T-cells. While the study requires more validation in other patients, it does offer the hope that regardless of the presence of an underlying malignancy, a stand-alone cure for HIV infections and diseases is possible in the near future.


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A new hope for COPD patients - Heparin to the rescue?

December 14th 2017, Posted by: Drug Repurposing Portal

Chronic obstructive pulmonary disease (COPD) is a mounting healthcare issue due to the limited availability of new cures for it, thereby accelerating its progressive impact on proper lung functioning and causing early deaths. A preliminary study conducted at the University of Portsmouth claims that an inhaled nebulized unfractionated form of common blood thinner, heparin, can potentially improve the symptoms of several respiratory diseases like COPD and cystic fibrosis. Further clinical evaluation is thus required to prove the long-term safety and efficacy of inhaled heparin, and hence its utility as a repurposed drug in patients with moderate-to-severe COPD.


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Chloroquine and Hydroxychloroqunine can be reprofiled to treat cancers

December 14th 2017, Posted by: Drug Repurposing Portal

Chloroquine (CQ) and Hydroxychloroquine (HCQ) are generic drugs that have been used over six decades as anti-malarial agents, and have subsequently also found use in treating lupus and rheumatoid arthritis. As part of the ongoing Repurposing Drugs in Oncology (ReDO) endeavors, new scientific studies have found that both CQ and HCQ may be used as anti-cancer agents, especially in combination with multiple conventional cancer therapies. CQ and HCQ exert their manifold anti-tumorigenic effects on both the tumor and its microenvironment, and deserve further clinical evaluation to be acknowledged as repurposed drugs.


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Bexarotene, an existing cancer drug, can potentially treat Huntington’s disease

December 12th 2017, Posted by: Drug Repurposing Portal

Huntington's disease is a fatal inherited disease that progressively results in neuronal degeneration in the brain, with no sure-shot medication to slow or stop its symptoms. There may however be hope in the form of Bexarotene, a US-FDA approved anti-neoplastic agent used for treating certain forms of lung cancer, breast cancer, cutaneous T-cell lymphoma, and Kaposi's sarcoma. As per the study published in the latest issue of Science Translational Medicine, Bexarotene and a drug similar in action and function, KD3010, activate the transcription factor PPARγ, which in turn improves mitochondrial health in neurons and enhances removal of damaged misfolded proteins as observed in a mouse model of Huntington's disease. Further validation is required in patients with Huntington's to determine and optimize the efficacy, dosage, and neuroprotective role(s) of Bexarotene.


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