Drug Repurposing News



Repurposing Bortezomib for viral infection

January 30th 2019, Posted by: Drug Repurposing Portal

Japanese encephalitis caused by the Japanese encephalitis virus (JEV) is an infection of the brain and has caused outbreaks in Southeast Asia and Western Pacific. There is no approved treatment for this disease. In a recent study published by researchers based in China, Systems biology methods were used to repurpose drugs for Japanese encephalitis virus. Using gene expression and phenome-wide association data of JEV and HotNet2 algorithm, 286 genes were identified. Enrichment analysis of these genes suggests that these genes are involved in viral infection pathways and immune response-related pathways. The anti-cancer proteasome inhibitor drug Bortezomib was shown to target several of the enriched genes. The researchers could show the ability of bortezomib to reduce viral infection in a JEV-infected mouse model. This study indicates that bortezomib might have the potential to be repurposed in the treatment of Japanese encephalitis.


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Repurposing of Ethyl bromopyruvate as broad-spectrum antibiotic

January 30th 2019, Posted by: Drug Repurposing Portal

Treatment of tuberculosis and infections caused by ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens is often ineffective due to acquired resistance. The present study reported antibacterial activity of ethyl bromopyruvate. It exhibited a dose-dependent antibacterial activity against both drug-susceptible and -resistant Mycobacterium (M.) tuberculosis and ESKAPE pathogens. Ethyl bromopyruvate was found to inhibit various enzymes of respiratory chain. Additionally, it elicited anti-bacterial activity equivalent to vancomycin at much lower concentrations. Based on these data authors recommend for repositioning of ethyl bromopyruvate as broad-spectrum antibacterial.


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Repurposing of Anti-fungal drugs in Leishmaniasis

January 30th 2019, Posted by: Drug Repurposing Portal

Protozoal parasites from the Leishmania genus cause the disease Leishmaniasis. Treatment of Leishmaniasis includes the use of pentavalent antimonials and Amphotericin. However, resistance to some of these compounds is common and hence there is a need for new therapeutic avenues. Scientists based in Brazil and the US have recently published a study where they tested the leishmanicidal activity of anti-fungal agents fenticonazole, tioconazole and nystatin. These drugs exhibited leishmanicidal activity by eliminating promastigote, intracellular amastigotes, and by interfering with parasite mitochondrion in some of the common Leishmania species. The most selective drugs towards amastigote forms were fenticonazole and nystatin. Fenticonazole was specifically able to alkalize infected host macrophages. Overall, these results suggest the possibility of repurposing antifungal drugs for leishmaniasis.


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Repurposing of antidepressant Clomipramine in leishmaniasis

January 30th 2019, Posted by: Drug Repurposing Portal

Most of the available antileishmanial drugs are expensive, toxic and not fully effective. Drug repurposing is an alternative strategy to develop novel therapeutic approaches. The authors of the present study demonstrated that antidepressant clomipramine induced mitochondrial depolarization and oxidative stress in Leishmania (L,) amazonesis. Moreover, the drug was able to act against the parasites at micromolar levels. Additionally, lipoperoxidation, plasma membrane permeabilization, apoptosis and autophagy hallmarks were noted in parasites after exposure to the drug. In summary, clomipramine interfered with redox metabolism of L. amazonesis leading to programmed cell death in parasites. These data suggest the prospective repurposing of clomipramine for leishmaniasis treatment.


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Repurposing of the Rheumatoid Arthritis drug Sulfasalazine against Neuroblastoma

January 22nd 2019, Posted by: Drug Repurposing Portal

Neuroblastoma (NB), a type of cancer that develops in the nervous system is one of the most common cancers seen in infants and young children. Current treatments are considered as inadequate owing to the high mortality and hence there is scope for innovative treatments. Scientists based in the US and the Netherlands have now shown that Sulfasalazine (SSZ), an FDA-approved drug for the treatment of ulcerative colitis and rheumatoid arthritis has anti-proliferative effects in NB tumor cells. The scientists could specifically show that SSZ was able to inhibit an enzyme known as Sepiapterin reductase (SPR), which is key in a pathway essential for NB tumor cell proliferation. Furthermore, it was seen that SSZ could inhibit the proliferation of NB cell lines as well as have anti-tumor effects in mice with xenografted NB tumors. This study suggests that FDA approved Sulfasalazine could be a promising candidate for being repositioned to arrest tumor growth in neuroblastoma.


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MEK inhibitors for the treatment of NF2-associated schwannomas

January 10th 2019, Posted by: Drug Repurposing Portal

The inactivation of NF2/merlin tumor suppressor gene might be associated with the development of Neurofibromatosis type 2 (NF2). The merlin gene product also modulates the activity of the Ras/Raf/MEK/ERK pathway. A research group from University of Central Florida has recently investigated the possibility of repurposing MEK1/2 inhibitors for NF2. The researchers screened mouse and human merlin-deficient Schwann cell lines (MD-MSC/HSC) against six MEK1/2 inhibitor drugs. Furthermore, efficacious drugs were tested in orthotopic allograft and NF2 transgenic mouse models. Among the six drugs investigated, Trametinib, PD0325901, and Cobimetinib were seen to be effective against NF2. These results support further investigation of MEK inhibitors in combination with other targeted drugs for NF2 schwannomas.


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Repurposing Idebenone as a novel chemotherapeutic agent for glioblastomas

January 10th 2019, Posted by: Drug Repurposing Portal

Idebenone, a synthetic analogue of the Coenzyme Q10, is commonly used to treat Alzheimer's disease, heart diseases, and several inherited disorders. A recent study however suggests its potential in glioblastoma (GBM) treatment. Idebenone was found to interfere not only with proliferation and migration of GBM cells, but also enhanced the cytotoxic effects of temozolomide and oxaliplatin. Further studies on repurposing idebenone as a chemotherapeutic aid in treating GBM and other cancer types are warranted.


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Evaluating the bone regenerating ability of the immunosuppressant drug Tacrolimus

January 10th 2019, Posted by: Drug Repurposing Portal

In a recent study, US based researchers have shown that the immunosuppressive drug tacrolimus, commonly used to reduce the risk of organ rejection after an allogenic organ transplant, may also have functional relevance in bone regenerative engineering. In an in vitro proactive screen in osteoprogenitor and primary cells to test the osteogenic effects of small-molecule drugs, tacrolimus showed long lasting osteogenic response with a short exposure of 24 hours. Repurposing tacrolimus as a promoter of osteogenesis might thus pave the way for designing effective strategies to repair and regenerate osteogenic tissues.


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Repurposing Tetramethylpyrazine in postoperative tissue adhesion

January 10th 2019, Posted by: Drug Repurposing Portal

Ligustrazine, also called tetramethylpyrazine (TMP), is widely used in traditional Chinese medicine to treat ischemic stroke, coronary heart disease, diabetic nephropathy, and knee osteoarthritis. A recent study has explored the anti-adhesion potency of TMP. This multi-link and multi-target role of TMP was attributed to its ability to inhibit collagen hyperplasia and overexpression of adhesion-related factors, thereby reducing the concentration of white blood cells and fibrin in plasma. Further basic and clinical evaluation is required to validate the repurposing potential of Tetramethylpyrazine (TMP).


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Repurposing common drugs for mental illness

January 10th 2019, Posted by: Drug Repurposing Portal

Psychiatric disorders such as bipolar disorder, schizophrenia, nonaffective psychosis are chronic and are often associated with self-harm and might require hospitalization. Current medication available for these disorders is often associated with adverse reactions. In a recent study, researchers at University College London have shown that commonly prescribed medications like anti-cholesterol drugs-statins, blood pressure drugs and type 2 diabetes drug- metformin might have beneficial effects in psychiatric patients. The researchers analyzed life-long medical records of 142,691 persons in Sweden suffering from schizophrenia, bipolar disorder or other severe mental illnesses. Comparative studies were conducted based on the number of times each person was admitted to a psychiatric hospital clinic when they were taking these common medications and when they were not. 10-20% reduction in the number of episodes was observed with medications in usage, signifying a potential role for repurposing these drugs to improve mental health outcomes. Further tests in clinical trials would be beneficial.


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Repurposing the old anti-helimenthic drug Niclosamide as an anti-fibrotic drug against pulmonary fibrosis

January 10th 2019, Posted by: Drug Repurposing Portal

A recent study by Indian researchers explores the possibility of repurposing the old anti-helminthic drug Niclosamide as an anti-fibrotic drug against Pulmonary Fibrosis (PF). PF is associated with scarring of lung and deposition of extracellular matrix and is often lethal. In the study, the authors investigated the anti-fibrotic potential of Niclosamide in an in-vitro model of pulmonary fibrosis and a 21-day model of Bleomycin induced PF in-vivo. The results demonstrated that Niclosamide might exert an anti-fibrotic effect by inhibiting fibrotic signaling, regulating WNT/β-catenin signaling, preventing fibroblast migration and decreasing epithelial-mesenchymal transition. The study findings suggest the potential for repurposing of Niclosamide as an anti-fibrotic agent for treatment of pulmonary fibrosis.


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Repurposing of Etravirine as a potential therapeutic for friedreich's ataxia

January 10th 2019, Posted by: Drug Repurposing Portal

Friedreich's ataxia is caused due to mutations in frataxin gene which results in decreased expression of frataxin. The current study aimed to identify approved drugs that can increase frataxin levels. Authors have performed a high-throughput screening of 853 FDA approved drugs to evaluate their effect on frataxin expression levels. Antiviral drug etravirine was further analyzed and found to increase frataxin levels in patient-derived cells. Additionally, etravirine treatment reduced oxidative stress in patient-derived cells by restoring aconitase enzyme activity. Based on these data and considering its excellent safety profile etravirine holds promise to be repurposed as a novel therapeutic candidate for Friedreich's ataxia.


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Repurposing Cisplatin to treat Pseudomonas aeruginosa infection

January 2nd 2019, Posted by: Drug Repurposing Portal

Emergence of acquired resistance of bacteria to a broad range of existing therapies urges for developing novel therapies. Drug repurposing is a time-saving and economical alternate approach to identify potential treatment strategies. The present study reported antibacterial activity of an anti-cancer drug cisplatin against Pseudomonas (P.) aeruginosa. Cisplatin was found to effectively kill various strains of P. aeruginosa, possibly via interfering DNA replication. Furthermore, cisplatin was also able to eradicate biofilms both in vitro and in vivo murine keratitis model. Further studies are warranted to evaluate the repurposing potential of cisplatin for treatment of P. aeruginosa infections.


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Repurposing proton pump inhibitor Omeprazole for multiple sclerosis

December 24th 2018, Posted by: Drug Repurposing Portal

A recent study published in Brain research discusses the potential of proton pump inhibitor Omeprazole for the treatment of multiple sclerosis. Analysis of genes, drugs and diseases connections by utilizing Connectivity Map identified that Omeprazole may have remyelinating potential. In vitro studies in primary oligodendrocyte precursor cells revealed that Omeprazole induce oligodendrocyte differentiation and maturation. Further in vivo studies in cuprizone-induced demyelination mouse model showed that Omeprazole (10 mg/kg) treatment for 2 weeks improved motor coordinative function, increased expression of myelin basic protein (MBP) and up-regulation in the expression of genes related to remyelination. Thus, both in vitro and in vivo studies indicate that Omeprazole is a promising repurposing candidate for the treatment of multiple sclerosis.


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Anti-hepatitis drug telbivudine repurposed to target SOD1 protein in ALS

December 17th 2018, Posted by: Drug Repurposing Portal

Research conducted by scientists based in Canada has revealed the potential of an anti-hepatitis drug to slow the progression of amyotrophic lateral sclerosis (ALS), also called Lou Gehrig's disease. The drug, known as telbivudine, targets the SOD1 protein that is misfolded in ALS patients. The scientists used computer simulations to screen for drugs with the potential to target SOD1, and likely candidates including telbivudine were tested in animal models. In these studies, telbivudine was shown to have low toxicity and was able to penetrate the blood brain barrier, which is an essential attribute for drugs intended as therapy in most neurological disorders. Telbivudine treatment improved the deficits associated with the SOD1 protein. Since telbivudine is used in the treatment of hepatitis, it is known to be safe in patients. Thus, telbivudine has the potential to be repurposed in the treatment of ALS.


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Repurposing the diuretic Spironolactone as an antischistosomal drug

December 17th 2018, Posted by: Drug Repurposing Portal

Schistosomiasis, caused by parasitic flatworms schistosomes, infects over 200 million people worldwide. There is just one drug praziquantel for the treatment of this disease. Researchers identified spironolactone, a diuretic, as an anti-schistosomal drug. At low concentrations (<10 μM) spironolactone alters motor activity and morphology of adult schistosomes. In mice harbouring either patent or pre-patent infections spironolactone, at a single dose (400 mg/kg) or daily for five consecutive days (100 mg/kg/day), significantly reduced worm burden, egg production, and hepatomegaly and splenomegaly. Taken together, these results indicate spironolactone as a promising repurposed drug for schistosomiasis.


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Insilico repurposing approaches for Neglected Diseases

December 17th 2018, Posted by: Drug Repurposing Portal

Neglected tropical diseases (NTDs) represent a heterogeneous group of communicable diseases that are found within the poorest populations of the world. World Health Organization (WHO) prioritized 23 NTDs that are endemic in 149 countries affecting more than 1.4 billion people that costs billions of dollars annually. The NTDs result from four different causative pathogens: protozoa, bacteria, helminth and virus. Many of these diseases lack effective treatments. Therefore, new therapeutics for NTDs are desperately needed. The present review summarized various high throughput screening and computational approaches that have been performed in recent years and suggests that machine learning models to be constructed to develop novel treatments.


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Repurposing potential of multiple sclerosis drug fingolimod in the treatment of anxiety

December 14th 2018, Posted by: Drug Repurposing Portal

Research has suggested that a drug named Fingolimod used in the treatment of multiple sclerosis might be have the potential to be repurposed for alleviating anxiety. Researchers based in Israel and Germany genetically engineered mice that have no expression (knockout i.e. KO) of a protein named Importin α5. This led to decreased anxiety in these mice. Further investigation suggested that Importin α5 plays a role in the signaling pathway associated with sphingosine-mediated anxiety. The anxiolytic behavior seen in these Importin α5 KO mice was mirrored in wild-type mice using the multiple sclerosis drug Fingolimod that activates the Sphingosine 1 phosphate (S1P) receptor, consequently enhancing Sphingosine signaling. This study suggests that the anxiolytic potential of Fingolimod and similar drugs might be worth further investigation.


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Repurposing Alzheimers drug PBT2 against antibiotic-resistant bacteria

December 12th 2018, Posted by: Drug Repurposing Portal

Existing antibiotic therapies are often ineffective due to acquired resistance of bacteria to a wide range of antibiotics. This urges for developing novel strategies to combat antibiotic resistance. University of Queensland-led research investigated the antibacterial properties of PBT2, metal transport drug. PBT2 was originally developed for Alzheimers and Huntingtons disease. The current study demonstrated that in combination with zinc, PBT2 exhibits antibacterial activity and disrupts cellular homeostasis in erythromycin-resistant group A Streptococcus (GAS), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE). Additionally, the study also showed that various antibiotics act synergistically with PBT2-zinc to enhance killing of resistant Gram-positive pathogens. These findings suggest for the potential of repurposing PBT2 against antibiotic-resistant bacteria


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Anticancer properties of antiviral agent ribavirin against ALL

December 12th 2018, Posted by: Drug Repurposing Portal

Recent studies have repurposed ribavirin, an anti-viral agent, as an anti-cancer agent. It is known to inhibit ElF4E signaling. ElF4E functions in a pro oncogenic manner by facilitating the expression of various oncogenes like myc, bcl2 and mcl1. In this article Urtishak KA et al. have presented repurposing of ribavirin to infant acute lymphoblastic leukemia (ALL) treatment. Ribavirin treatment reduced the proliferation of ElF4E expressing ALL cells derived from infant patients. Additionally, in MT2A-rearranged (KMT2A-R) infant ALL cells and the KMT2A-AFF1 cell line, ribavirin treatment reduced proliferation with concomitant decrease in ElF4E activation. This study projects ribavirin as a promising drug for ALL.


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Tamoxifen target GPER is a novel mechanoregulator of pancreatic cancer

December 11th 2018, Posted by: Drug Repurposing Portal

Being an agonist of the G protein-coupled estrogen receptor (GPER), Tamoxifen is widely used in clinics to treat estrogen receptor positive breast cancer. In this study, tamoxifen has been reported to modulate the tumor microenvironment (TME) by inhibiting myofibroblastic differentiation of pancreatic stellate cells (PSCs). Tamoxifen mediated obstruction of extracellular matrix, prevention of cancer cell invasion, and reduced recruitment and polarization of M2 type tumor-associated macrophages in the pancreatic cancer TME. Hence, tamoxifen may be repurposed to modulate the TME of the pancreatic cancer and possibly other solid tumors.


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Drug repositioning identifies potential anti-epilepsy drugs

December 11th 2018, Posted by: Drug Repurposing Portal

A multidisciplinary strategy employed by researchers from University of Iowa combined gene expression profiling and bioinformatics to identify compounds which might be potential anti-seizure candidates. Differentially expressed genes between diseased (seizing) brain tissues in comparison to non-seizing tissue were analyzed and compared to the signatures of connectivity map database. Total of 184 compounds which includes 91 FDA-approved drugs with potential to reverse seizure expression pattern were identified. Finally, three drugs comprising metformin (diabetes drug), nifedipine (hypertension medication) and pyrantel tartrate (antiparasitic) showed significant seizure reduction in zebrafish model.


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Repurposing potential of Suramin against metastasis of breast cancer to the lungs

December 4th 2018, Posted by: Drug Repurposing Portal

Suramin is a drug used in river blindness and African sleeping sickness therapy. It has been withdrawn from the market due to its narrow therapeutic window and associated side effects. Various clinical trials have also tested it's potential for anti-cancer therapy. As evidence of the repurposing potential of Suramin, US based researchers working to find a cure for triple negative breast cancer (TNBC) have shown in in-vitro experiments that a combination of Suramin-glycol chitosan and doxorubicin nanoparticles could inhibit cancer cell migration, invasion and angiogenesis. Furthermore, an animal model for TNBC lung metastasis treated with these nanoparticles shows significant reduction in tumor burden and an extended lifespan with along with reduced cardio and renal toxicities that are generally associated with doxorubicin and Suramin respectively. This system could provide translatable solutions in the treatment of TNBC.


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Drug Repurposing for Rare Diseases Conference 2019

November 30th 2018, Posted by: Drug Repurposing Portal

Findacure's Drug Repurposing for Rare Diseases Conference is returning for its sixth consecutive year! Held in celebration of Rare Disease Day, the event will unite the rare disease community to showcase innovative and groundbreaking drug repurposing projects that can bring real change to those living with rare diseases. The conference, taking place on 27th February 2019 at the Royal College of Nursing.


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Repurposing anti-viral drug ribavirin in pediatric osteosarcoma

November 30th 2018, Posted by: Drug Repurposing Portal

Recent studies proposed the prospective use of anti-viral drug ribavirin for cancer treatment. In similar lines, the current study demonstrated that ribavirin enhances chemosensitivity in osteosarcoma. Additionally, Ribavirin is found to inhibit growth and induce apoptosis in pre-clinical osteosarcoma cell and xenograft models at clinically relevant concentrations. Interestingly, ribavirin did not affect human normal osteoblastic cell and fibroblasts. Authors of the present study demonstrated that anti-tumor functions of ribavirin are mediated by targeting eIF4E, ERK, EZH2 and Snail pathways. These data provided fundamental evidence of repurposing ribavirin for the treatment of osteosarcoma.


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Antibacterial activity of metformin, propranolol and amitriptyline

November 30th 2018, Posted by: Drug Repurposing Portal

Kapoor et. al, department of Biotechnology, ISF Institute of Professional Studies (ISFIPS), India conducted in silico and in vitro studies on various existing drugs including metformin (Anti-diabetic), propranolol (Anti-hypertensive), and amitriptyline (antidepressant) and showed that they have antibacterial activity against Bacillus pumilus, Pseudomonas aeruginosa and Staphylococcus aureus. Here by they could be promising agents for various infectious diseases.


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Derivatives of anti malarial drug amodiaquin are promising therapeutics against Ebola infection

November 30th 2018, Posted by: Drug Repurposing Portal

Robert Davey and his team from Boston University School of Medicine discovered that certain derivatives of amodiaquine, a medication typically used to treat malaria, could provide a new therapeutic approach to treating patients infected with Ebola. The team tested nearly 70 amodiaquine derivatives and found that anti Ebola activity of amodiaquine was increased by modifying the alkyl chains extending from the aminomethyl group and a halogen bonded to the quinoline ring. These modifications, when combined, could increase the selectivity index of the parent amodiaquine by about 10 folds. This study paves the way for further investigation of the therapeutic potential of amodiaquine derivatives against Ebola infection.


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Antibiotic used for acne could act against age related neurodegenerative diseases

November 29th 2018, Posted by: Drug Repurposing Portal

Minocycline is a regulatory agency-approved antibiotic used to treat acne, but the compound has also long been known to reduce tumor growth, inflammation, and protein aggregation in mammals, albeit by an unknown mechanism of action (MOA). Authors in this study, show that the antibiotic minocycline increases lifespan and reduces protein aggregation even in old, stress signalling pathways (SSP) deficient Caenorhabditis elegans by targeting cytoplasmic ribosomes, preferentially attenuating translation of highly translated mRNAs. Authors propose that this drug reduces the concentration of aggregation prone protein by inhibiting translation. Aged individuals having defective SSP could be benefited from minocycline induced inhibition of cytoplasmic translation which could reduce protein aggregation and thus, protein aggregation induced pathologies like neurodegenerative disease.


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Repurposing anti-inflammatory methotrexate against cardiovascular disease

November 28th 2018, Posted by: Drug Repurposing Portal

Atherosclerosis leading to cardiovascular disease is a leading cause of global mortality. Research has suggested that inflammation and immune activation along the arterial wall contributes to atherosclerosis. A substantial percentage of patients administered standard treatment continue to have residual cardiovascular risk. The use of anti-inflammatory drugs in cardiovascular disease management is being explored. Methotrexate, a folic acid analogue is used in the treatment of rheumatoid arthritis and autoimmune conditions. Methotrexate alleviates the risk of cardiovascular events in rheumatoid arthritis patients possibly through changes in blood pressure, arterial stiffness and insulin resistance. It's ability to modulate the levels of pro and anti-atherogenic cytokines and activate the protective 5' adenosine monophosphate-activated protein kinase (AMPK) might be worth investigating. Methotrexate might be a candidate for repurposing in cardiovascular therapy once studies help to clarify associated parameters such as dosage, adverse events etc.


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Antimicrobial imidazole and derivatives used against Newcastle disease virus infection in chicken

November 27th 2018, Posted by: Drug Repurposing Portal

Newcastle disease virus (NDV) that afflicts poultry is the cause of a global epidemic and poses an economic burden. Prevention of NDV infection through vaccination is challenging due to its evolving genetic variability. There is an urgent need for therapeutics that resist its evolution and drug repurposing might provide a practical solution. In a recent study, researchers in India have repurposed the antimicrobial compound Imidazole and its derivatives to investigate their abilities in the control of NDV. Sub-lethal doses of Imidazole were checked for their anti-viral properties in cells, in eggs and even in chickens. Imidazole treated chickens produced the antiviral type I Interferon and did not shed the virus. This study suggests that Imidazole and its derivatives might be repurposed in the treatment of the Newcastle disease virus.


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Antitubercular drug isoniazid repurposing in prostate cancer

November 23rd 2018, Posted by: Drug Repurposing Portal

Clinical efficacy of existing prostate cancer therapies is limited in patients with advanced disease suggesting the requirement of alternative therapeutic strategies. Monoamine oxidase A (MAOA) levels are found to be elevated with prostate cancer aggression and metastasis. In line, MAOA inhibitor therapies have been shown to reduce the metastasis in prostate cancer mouse models. Additionally, the present study demonstrated the anti-cancer activity of MAOA inhibitor isoniazid (INH)- NIRF heptamethine dye conjugate in prostate cancer PC-3 cells. Taken together these data suggest that INH-dye conjugates have great potential to be used as versatile antitumor agents in prostate cancer.


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Drug used against Migraine has potential therapeutic value in breast cancer

November 20th 2018, Posted by: Drug Repurposing Portal

Aggressive basal-like breast cancer (BLBC), which is a form of triple negative breast cancer, lakhs any targeted therapy and has poor prognosis. BLBC's transformation and growth is driven by N-Ras. Authors in this study screened pharmacologically active compounds for their ability to induce N-Ras degradation which led to the identification of flunarizine (FLN), previously approved for treating migraine and epilepsy. FLN induced autophagy dependent degradation of N-Ras and FL treatment inhibited the growth of cell culture (in vitro) and xenograft (in vivo) models of BLBC. Hence, this study describes the potential repurposing of flunarizine, which is a low toxicity drug approved for epilepsy and migraine, to treat aggressive basal like breast cancer


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Targeting of zinc finger transcription factors in cancer by thalidomide analogs

November 19th 2018, Posted by: Drug Repurposing Portal

Thalidomide, a drug used against morning sickness 60 years ago was recalled after it was associated with birth defects. Recently, thalidomide and its derivatives have been used against multiple myeloma. Transcription factors play a role in several cancers but are difficult to target since they do not have drug binding sites. Thalidomide and its analogs target transcription factors for cellular degradation by recruiting their C2H2 zinc finger motifs to a protein named Cereblon that is part of the cellular protein degradation machinery. In a study by researchers based in the USA, Switzerland and Germany, zinc finger proteins were screened for degradation in the presence of thalidomide analogs. It was found that up to 150 zing finger domains bind to thalidomide analog-Cereblon complex in vitro. Selective degradation of zing fingers can be achieved by modification of the compounds. This suggests the potential of thalidomide and its analogs to be repurposed to target zinc finger transcription factors that have previously been difficult to target.


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Anti-trypanosomal drug Suramin could be repurposed against oral cancer

November 18th 2018, Posted by: Drug Repurposing Portal

HuR is an RNA binding protein that is associated with mRNA transcribed from growth related genes. It is highly expressed in cancer cells. HuR knockdown mitigates the malignant phenotype in some cancer types. Japanese researchers screened 1570 compounds from the approved drugs library to find drugs that can target HuR. In this screen, Suramin, an anti-trypanosomal drug was found to bind HuR. Consequently, Suramin was found to downregulate mRNA and protein expression of certain growth-related genes. Studies in tongue carcinoma cell line showed that cells treated with Suramin reported lower motility and invasive activities than control cells. Thus, the repurposing of Suramin to target HuR might offer an alternative therapy in the treatment of oral cancer.


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Repurposing azithromycin and rifampicin against Gram-negative pathogens in combination with peptide potentiators

November 14th 2018, Posted by: Drug Repurposing Portal

A research group from the University of Copenhagen, using combinatorial screening, identified that azithromycin and rifampicin in combination with peptide potentiators could inhibit the growth of several strains of E. coli, K. pneumoniae and Acinetobacter baumannii. These data demonstrate the repurposing potential of combination of peptides with azithromycin and rifampicin against Gram-negative multidrug-resistant bacteria. However, further studies are warranted to validate the use of this combination against Gram-negative pathogens


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Rare diseases entail new funding methods

November 13th 2018, Posted by: Drug Repurposing Portal

Out of ~7000 rare diseases identified so far, approved therapies are available for only around 400 rare diseases. To accelerate the discovery of affordable new therapies for those living with rare diseases, European Medicines Agency proposes a new, innovative thinking and funding model highlighting the Drug repurposing and de-risking strategies.


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Dronedarone used to control abnormal heart rhythms can be re-purposed against breast cancer

November 13th 2018, Posted by: Drug Repurposing Portal

Antiarrhythmic Drug, Dronedarone, has been shown to be cytotoxic for breast cancer cell lines. Dronedarone showed concentration dependent cytotoxity in 18 breast cancer cell lines tested at clinically relevant concentrations. Authors also tested the effect of this drug in in vivo setting. The cell line that showed high IC50 value for in vitro cell death experiments also showed the tumor growth inhibition in in vivo experiments. The dose of Dronedarone was 20 mg/kg which is clinicaly relevant. Hence, the therapeutic potential of anti arrhythmic drug Dronedarone can also be explored against breast cancer.


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Prospective repurposing opportunities for apomorphine

November 8th 2018, Posted by: Drug Repurposing Portal

Apomorphine is a non-selective dopaminergic agonist used in the treatment motor fluctuations in Parkinson's disease. Various research studies proposed other possible uses for apomorphine. To further explore the potential therapeutic and diagnostics applications of apomorphine, the present study reviewed the role of apomorphine from the available literature up to July 2018 in PubMed and Google Scholar databases. This review provides a comprehensive summary of pharmacological targets and biological functions of apomorphine in other neurological diseases like restless legs syndrome, Huntington's chorea, amyotrophic lateral sclerosis, Alzheimer's disease and disorders of consciousness as well as in sexual disorders, neuroleptic malignant(-like) syndrome and cancer.


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Repurposing potential of Antihypertensive medication against Alzheimer's disease

November 2nd 2018, Posted by: Drug Repurposing Portal

Researchers based in the US have found that a certain class of Antihypertensive (AHT) medications known as Angiotension-II receptor blockers (ARB) might alleviate the risk of Alzheimer's disease (AD) in certain populations. The researchers analyzed the claims of medicare beneficiaries and compared Alzheimer's disease (AD) diagnosis rates of six different AHT drug treatments in persons 65 years and above. ARBs were found to reduce the risk of AD in white men and white and black women. No association was observed in Hispanic women and men. Thus, in conclusion the use of certain AHTs might not only help in dealing with hypertension, but also reduce the risk of Alzheimer's disease.


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Alexidine dihydrochloride is a promising broad-spectrum antifungal

November 1st 2018, Posted by: Drug Repurposing Portal

Emergence of drug resistance is the major challenge in the treatment of invasive fungal infections due to Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans in hospitalized immunocompromised patients. Researchers from Los Angeles Biomedical Research Institute at Harbor, University of California at Los Angeles (UCLA) Medical Center, screened the New Prestwick Chemical Library of 1,200 FDA-approved, off-patent molecules to identify the drugs that inhibit that inhibit growth of all three pathogens. The team has identified alexidine dihydrochloride (AXD), a drug approved as a topical antimicrobial and anti-plaque agent, as the drug with the greatest antifungal and anti-biofilm activity against a diverse range of fungal pathogens. Further studies are warranted to repurpose AXD as pan-antifungal and antibiofilm drug.


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Smooth muscle relaxant Papaverine could have repurposing potential to aid in anti-cancer radiation therapy

November 1st 2018, Posted by: Drug Repurposing Portal

Use of radiation in anti-cancer therapy is hampered by the hypoxic micro-environment of tumors. This limits the molecular oxygen exposure that aids in the killing of tumor cells by causing irreversible damage to the tumor cell DNA. Increasing tumor oxygenation aids radiation therapy in killing tumor cells. Decreasing mitochondrial respiration causes a decrease in the tumor oxygen demand, thereby increasing tumor oxygenation and radiation response. Papaverine, a drug in use since the 19th century as a smooth muscle relaxant has been found to inhibit the mitochondrial complex I. Evidence suggests this action leads to increased oxygenation and enhanced radiation response. Papaverine derivatives could potentially be used as clinical radiosensitizers with fewer side effects. This strategy would not sensitize well-oxygenated normal tissue, increasing efficiency of radiotherapy.


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Repurposing inflammatory bowel disease drug for HIV treatment

November 1st 2018, Posted by: Drug Repurposing Portal

Vedolizumab, which is anti alpha-4beta-7 integrin antibody (a4b7), has been used in the management of inflammatory bowel disease. Naive T and B cells express integrin a4b7, which mediates their migration into the immune inductive sites in intestine. During acute HIV infection, HIV also localizes to gastrointestinal tract and infects T-cells. A direct interaction between a4b7 and the HIV viral envelope has also been observed. Thus anti a4b7 therapy holds promise in HIV therapy. The present study reveals the safety and tolerability of Vedolizumab in HIV patients. This study shows that Vedolizumab therapy does reduce the lymphoid aggregates in intestine which is a site of persistent replication of HIV. Thus, a new therapeutic approach against HIV infection by repurposing a drug used for inflammatory bowel disease is proposed.


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Successful Phase II trial of plaque psoriasis drug Stelara for the treatment of Lupus

October 30th 2018, Posted by: Drug Repurposing Portal

Ustekinumab/Stelara is approved for plaque psoriasis, psoriatic arthritis and Crohn's disease. Seltara has been in a year-long worldwide Phase 2 clinical trial for systemic lupus erythematosus (SLE) or lupus. Based on the insignts from a combined approach that uses evidence-based CoLT scoring system and pathway-based LuGENE, a Big Data, Machine Learning methodology, AMPLE Biosolutions priotitized Stelara for repositioning into lupus. In line, Janssen reported recently that Seltara has an excellent safety profile and reduced lupus disease activity in Phase II trial. In addition, Janssen has announced at the annual ACR meeting of physician-scientists specializing in rheumatic and autoimmune diseases that Seltara a promising candidate for the Phase 3 trials for lupus. This is a classic example of de-risk repositioning of existing FDA-approved drugs for alternate indications.


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REPO-TRIAL Programme for drug repurposing and endophenotyping

October 29th 2018, Posted by: Drug Repurposing Portal

Harald Schmidt, recipient of ERC Advanced Investigator, Europe's most prestigious research award, is engaged in developing an innovative in-silico based approach to improve the efficacy and precision of drug repurposing trials. He is one of the chief speakers in International Conference on Bioinformatics and Biomedicine to be held at Madrid, from 3rd to 6th December 2018,


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Bromocriptine repurposing in cancer therapy.

October 26th 2018, Posted by: Drug Repurposing Portal

Bromocriptine, dopamine D2 receptor agonist is used in the therapy of Parkinson's disease, acromegaly, hyperprolactinemia, infertility, galactorrhea, and type-2 diabetes as well. It is also used in the treatment of hormone-dependent pituitary tumors. The current study evaluated the effect of bromocriptine on hormone-independent and multidrug-resistant tumors. As expected, bromocriptine was found to be cytotoxic against various drug-sensitive as well as multidrug-resistant cancer cell lines. In parallel authors have also demonstrated that bromocriptine inhibited NF-kB, an important factor in cancer progression, indicating that cytotoxic functions of bromocriptine are mediated by targeting NF-kB. All these data suggest that bromocriptine is a promising candidate for repurposing in cancer therapy.


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Drug repurposing insights from RNA-seq transcriptomic profiles for rare neurogenetic diseases

October 17th 2018, Posted by: Drug Repurposing Portal

Disease-modifying drugs are available for only 5% of the rare monogenic diseases. Drug repurposing is an economically viable and faster alternative for identifying novel therapies for rare diseases. In an attempt, researchers from university of Ottawa and Pfizer pharmaceutical company used RNA sequencing to generate transcriptomic profiles of cerebrocortical cultures treated separately with 218 blood-brain barrier (BBB) penetrant drugs. The current study aimed to identify therapeutically relevant hidden drug-target associations that might provide drug repurposing insights for rare neurogenetic diseases. Interestingly, the authors have created a transcriptome-wide searchable database for easy access to gene expression data resulted from this study to promote the discovery of new molecular links between 218 clinic-tested BBB penetrant drugs and genes associated with various neurologic disorders.


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Prodrug dimethyloxalylglycine used in hypoxia signaling repurposed to target glutamine dependent cancer metabolism

October 15th 2018, Posted by: Drug Repurposing Portal

A team of U.S. and U.K. based researchers has shown that the drug Dimethyloxalylglycine (DMOG) used to study hypoxia can also be used to inhibit glutamine metabolism. This could lead to a way to repurpose DMOG to target glutamine dependent cancer cells by starving them off glutamine. DMOG is an alpha-ketoglutarate (αKG) analog that is transported into cells by monocarboxylate transporter 2 (MCT2). DMOG undergoes intracellular hydrolysis to methyloxalylglycine (MOG) resulting in the inhibition of enzymes involved in glutamine metabolism and decreased levels of tricarboxylic acid. Also seen was decrease in ATP production and reduced mitochondrial respiration. Thus, DMOG mediated inhibition of glutamine metabolism eventually leads to cell death.


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CNS drug sertraline shows promise to be repurposed for Leishmaniasis

October 11th 2018, Posted by: Drug Repurposing Portal

Sertraline, a selective serotonin reuptake inhibitor (SSRI) indicated for depression, obsessive compulsive disorder, anxiety and post-traumatic stress disorder (PTSD) has shown promise for the treatment of visceral leishmaniasis. A study in murine models showed that sertraline induced respiration uncoupling, significant decrease of intracellular ATP level, and oxidative stress in L. infantum promastigotes. In addition, sertraline also caused metabolic disarray leading to shortage of metabolic fuel used by Leishmania. Thus, repurposing sertraline which has a well defined pharmacology with mild side effects is an attractive option for the treatment of the infectious disease leishmaniasis.


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Antifungal ciclopirox repurposed against Gunther's disease

October 9th 2018, Posted by: Drug Repurposing Portal

Congenital erythropoietic porphyria or Gűnther's disease, currently lacks curative treatments. The disease affects many organs can be life-threatening, is a rare autosomal recessive disease produced by deficient activity of uroporphyrinogen III synthase, the fourth enzyme in the heme biosynthetic pathway. The pathology results from reduced heme production and accumulation of uroporphyrin by-product. An existing antifungal drug, ciclopirox (CPX), was discovered as a binding partner of uroporphyrinogen III synthase. It was observed that cicopirox binds at an allosteric site without disturbing UROIIIS's catalytic function and restores the enzyme's activity. The drug has also been shown to improve symptoms associated with congenital erythropoietic porphyria in genetic mouse models of the disease. Thus, this study paves the way for an antifungal to be potentially repurposed for Gűnther's disease.


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Drug repurposing research facilitated by ReFRAME identifies novel use for existing drugs

October 8th 2018, Posted by: Drug Repurposing Portal

ReFRAME, developed by scientists at Calibr, a part of Scripps Research is a comprehensive repository of data on more than 12,000 small-molecule drugs by combining three widely-used commercial drug databases like Excelra GoStar, Clarivate Integrity, and Citeline Pharmaprojects. New study using ReFRAME has identified two compounds, VB-201 and a structurally related analogue of ASP-7962, to be efficacious in animal models of Cryptosporidium infection, a major cause of severe diarrhea. Two other drugs; leprosy drug clofazimine and the arthritis drug auranofin are being clinicaly tested for cryptosporidiosis in HIV positive patients and tuberculosis repectively.


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Antibiotic doxycycline repurposed to target cancer stem cells

October 3rd 2018, Posted by: Drug Repurposing Portal

A research team from Italy and U.K. has found that the antibiotic Doxycycline, an inhibitor of mitochondrial biogenesis effectively reduces cancer stem cells (CSCs) in early breast cancer patients. CSCs play a role in tumor initiation, spread and recurrence and are known to over-express important mitochondria-related proteins. Doxycycline is effective in the treatment of a variety of bacterial infections including respiratory tract infections, sexually transmitted infections, ophthalmic infections etc. In this study, the administration of doxycycline to breast cancer patients before surgery significantly reduced known biomarkers of "stemness" (CD44, ALDH1) that are expressed on CSCs, indicating a decrease in these harmful cells. Thus, the repurposed Doxycycline could be an effective option to eradicate CSCs and treat breast cancer.


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Opioid antagonist buprenorphine - a new option for treating pain in sickle cell anemia

September 30th 2018, Posted by: Drug Repurposing Portal

Pain associated with sickle cell anaemia presents an unmet medical need. Doctors has been prescribing opioids for pain relief but risk of addiction to these drugs remains a daunting problem. Dr. Ify Osunkwo, one of the researchers at Atrium Health has identified buprenorphine as a repurposed drug for being used as a pain killer in sickle cell anaemia. This drug has been used as a part of therapy to combat addiction to opioid drugs. In a study involving 50 patients, Dr Osunkwo found encouraging results with buprenorphine.


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EGFR inhibitors repurposed to degrade cancer-associated tribbles 2 pseudokinase

September 25th 2018, Posted by: Drug Repurposing Portal

Elucidating the function of pseudokinases is tricky, owing to a paucity of target-validated small molecule compounds. Tribbles 2 (TRIB2) is a cancer associated pseudokinase with a varied interactome that includes the canonical AKT signaling molecule. TRIB2 aids in tumor survival and drug resistance and hence is of therapeutic interest. Scientists have found that TRIB2 is targeted by small-molecule protein kinase inhibitors originally designed to inhibit EGFR family members. A drug repurposing approach elucidated that these compounds, including the drug afatinib led to rapid TRIB2 degradation in human AML cancer cells, affecting their survival and signaling. This study provides new drug leads for TRIB2 degrading compound development and underlines that off target effects of small molecule induced protein degradation might elicit further pseudokinase targeting inhibitors.


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Repurposing of nitroxoline or nelfinavir or both in combination with erlotinib in pancreatic cancer

September 21st 2018, Posted by: Drug Repurposing Portal

Several recent studies evaluated the repurposing potential of approved anti-infectives nitroxoline and nelfinavir in cancer at pre-clinical as well as at clinical levels. In line, the current study also demonstrated the anti-tumor functions of nitroxoline and nelfinavir as single agents or in combination in various pancreatic cancer cell lines. Interestingly, the anti-tumor effect of combined treatment of nitroxoline and nelfinavir is further enhanced in the presence of an approved pancreatic cancer drug erlotinib. These data suggest the rationale for repurposing of these approved anti-infectives as single agents or in combination for treatment of pancreatic cancer.


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Discovery of over 500 new genes linked to blood pressure opens up new avenues of drug repurposing

September 18th 2018, Posted by: Drug Repurposing Portal

In a recent study published in Nature genetics, researchers at Queen Mary University and Imperial College London have reported the discovery of 535 novel genetic loci linked to blood pressure after analysing samples of over a million patients. Besides giving unprecedented insights into the regulation of blood pressure, this study has also presented an opportunity for drug repurposing strategies. Many novel genes systems reported in this study are known to play role in other diseases like Alzheimer's disease, diabetes, cancer and autoimmune disorders. The study indicates some potential new targets for drug development and suggests that some drugs prescribed for other diseases could be repurposed for treating hypertension. For example, one of the newly discovered gene regions is targeted by the type 2 diabetes drug canagliflozin.


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Tazarotene, an approved drug for psoriasis and acne is a promising therapy for Hepatitis virus infection

September 17th 2018, Posted by: Drug Repurposing Portal

Tazarotene, a retinoic acid receptor (RAR) agonist is approved for plaque psoriasis and acne. A recently published study in Antimicrobial Agents and Chemotherapy has proposed tazarotene as an anti-Hepatitis B virus (anti-HBV) agent. In this study, authors have performed a drug repurposing screen of Food and Drug Administration (FDA)-approved compounds to identify novel anti-HBV agents. Numerous RAR agonists were found to reduce the HBsAg levels in a dose-dependent manner. Moreover, tazarotene was demonstrated to have a potent anti-HBV effect in HBV-infected dHepaRG models. It was shown to repress the activation of HBV promoters and HBV cccDNA transcription. These findings suggest RAR agonists including tazarotene have the potential to be repurposed as novel anti-HBV agents.


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Drug repurposing for targeting Hippo pathway effectors YAP/TAZ/TEAD

September 14th 2018, Posted by: Drug Repurposing Portal

Several clinical drugs are reported as modulators of the Hippo pathway effectors YAP (Yes1-associated protein), TAZ (transcriptional co-activator with PDZ-binding motif), and TEAD (transcriptional enhanced associate domains) which directly regulate cell growth and tissue homeostasis. Since the Hippo pathway is known to cross-talk with several signaling pathways, efforts are being made to understand its importance in oncology. This study highlights the main mechanisms of action of clinically approved or investigational drugs that can modulate the Hippo pathway, and help to find potential strategies for discovering new lead compounds.


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In silico tools and approches for respiratory disorders

September 14th 2018, Posted by: Drug Repurposing Portal

Increase in global burden of respiratory diseases like asthma, COPD, and lung cancer indicates the necessity to develop novel approaches for prevention/treatment and identification of biomarkers for early detection and patient stratification. Techniques like next-generation sequencing and mass spectrometry are generating huge amounts of data at various levels of biological regulation. Sophisticated bioinformatics and statistical tools are required to analyze, understand and gain new intuitions from this wealth of data. In the current study authors have reviewed the basic concepts in bioinformatics and genomic data analysis and exemplified the utility of these tools to better understand the pathogenesis of lung diseases. This review also highlights that the integration of multiomics data with computational drug repurposing approaches might be useful to identify novel therapeutic targets for personalized medicine.


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Repurposing cancer drugs and antidepressants to treat "brain-eating" amoebic diseases

September 13th 2018, Posted by: Drug Repurposing Portal

Blood brain permeable breast cancer drug Tamoxifen and antidepressant Prozac have the potential to inhibit the growth of the amoeba Naegleria fowleri in vitro. This inhibitory effect is mediated by the activity of the drugs on the sterol biosyntehsis pathway in N. fowleri. In comparison to miltefosine, an investigational drug recommended by the U.S. Centers for Disease Control and Prevention (CDC) for treating primary amoebic meningoencephalitis, a combination of Tamoxifen and Prozac treatment was found to be more potent at lower concentrations. Since the economic incentives to develop new drugs to treat such rare diseases is low in the pharma industries, drug repurposing appears to be a better alternative for these fatal diseases.


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Repurposing potential of pyronaridine in tuberculosis treatment

September 13th 2018, Posted by: Drug Repurposing Portal

Pyronaridine is a European Union (EU)-approved antimalarial drug. A recent study verified its activity in vitro against Mycobacterium tuberculosis. Interestingly, authors also found that the pyronaridine functioning is similar to that of a known antituberculosis drug rifampicin. Additionally, pyronaridine synergized the rifampicin activity in vitro when treated together. Surprisingly, pyronaridine also demonstrated activity against rifampicin resistant form of M. tuberculosis alone, as well as in combination with rifampicin. Future studies are warranted to evaluate the potential use of pyronaridine as an adjunct treatment against M. tuberculosis infection.


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An old antimalarial drug finds new purpose against retinal neovascularization

September 12th 2018, Posted by: Drug Repurposing Portal

Neovascularization is the hallmark of various retinal diseases including diabetic retinopathy, wet age-related macular degeneration (AMD), and other conditions. Apelin and its receptor have been shown to have a crucial role in both developmental and pathological angiogenesis in the eye. A research team at Sanford Burnham Prebys Medical Discovery Institute (SBP) found that the antimalarial drug amodiaquine can inhibit apelin receptor protein, and proposed that amodiaquine is a potential drug repurposing candidate for the treatment of retinal neovascularization. As the drug has been approved to treat malaria for decades, the path to reach out to retinal disease patients could be relatively shorter and streamlined.


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Repurposing mebendazole for treating triple negative breast cancer

September 6th 2018, Posted by: Drug Repurposing Portal

Triple negative breast cancer (TNBC) remains the most challenging type of breast cancer to treat due to recurrence. Authors of the current study hypothesized that breast cancer cells that survive radiation therapy might get reprogrammed into cancer-initiating cells. A high-throughput screening was performed to identify drugs that target cancer-initiating cells. Antiparasitic drug mebendazole exhibited cytotoxicity towards TNBC cells. Anti-tumor activity of mebendazole was verified by various in vitro and in vivo assays. Interestingly, mebendazole also prevented the radiation-induced conversion of breast cancer cells into treatment resistant cancer-initiating cells. Altogether, these data suggest the prospective repurposing of mebendazole in combination with radiation therapy in TNBC treatment.


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Can mitochondrial dysfunction in Alzheimer's disease be resolved by repurposing a liver disease drug?

September 5th 2018, Posted by: Drug Repurposing Portal

A new research study published in the Journal of Molecular Biology has revealed that ursodeoxycholic acid (UDCA), used to treat liver diseases for decades, could restore and improve mitochondrial dysfunction, a known causative factor of sporadic or familial Alzheimer's disease (AD).


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Discovery of new antifungal inhibitors of oxidosqualene cyclase through virtual screening and drug repositioning strategies

September 5th 2018, Posted by: Drug Repurposing Portal

Though the mortality rate due to Candidiasis fungal infection is significant, the therapeutic treatment is limited and requires a search for new drugs and targets. The enzyme oxidosqualene cyclase (OSC), an intermediate of ergosterol, constitutes an attractive therapeutic target. The current study provides important insights for the development of new oxidosqualene cyclase inhibitors as antifungals. It identifies potential inhibitors of C. albicans OSC (CaOSC) from a database of marketed drugs. By molecular docking of known inhibitors, researchers of the current study identified calcitrol, the active form of vitamin D, and four other drugs as potential inhibitors of CaOSC.


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Repurposing an old Tuberculosis vaccine for Diabetes and Fibromyalgia

September 5th 2018, Posted by: Drug Repurposing Portal

Two innovative clinical studies lead by the Massachusetts General Hospital are exploring the efficacy of the Bacillus Calmette-Guerin (BCG) vaccine, an old tuberculosis vaccine, in treating both diabetes and fibromyalgia. Mass General reported results of a long-term follow-up of participants in clinical trials of the BCG vaccine to reverse advanced type 1 diabetes, including the restoration of near-normal blood sugar levels.


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Potential repurposing of antidepressants for Alzheimer's disease

August 30th 2018, Posted by: Drug Repurposing Portal

The nuerodegenrative disorder, Alzheimer's disease remains a therapeutic challenge as there is no effective therapy available to prevent the neurodegeneration caused by amyloid plaque formation. Selective serotonin reuptake inhibitors like fluoxetine and paroxetine are FDA approved anti-depression drugs. Both these drugs were found to reduce amyloid-beta42 aggregation and fibrilogenesis considerably. NMR studies show that these molecules directly bind to amyloid aggregates and thus inhibit fibrilogenesis. These selective serotonin inhibitors have great potential in therapeutic management of Alzheimer's disease pathology.


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New prospects for repositioning ritanserin in cancer

August 29th 2018, Posted by: Drug Repurposing Portal

Ritanserin, a serotonin receptor inverse agonist reported to target novel kinases, was evaluated as a drug candidate for treating several neuropsychiatric disorders but never received clinical approval. The authors of the current study have shown the use of ritanserin to induce apoptotic cell death in NSCLC and SCLC via serotonin independent mechanisms. Authors used quantitative chemical proteomic analysis to show that ritanserin specifically targeted c-RAF in the SCLC subtype, with negligible activity against other kinases. These results might have implication in the use of ritanserin to target c-RAF in RAS-mutant cancers that are resistant to clinical BRAF inhibitors, thereby opening new prospects for repositioning ritanserin in cancer.


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Use of veterinary drugs in humans - a possible repurposing opportunity?

August 27th 2018, Posted by: Drug Repurposing Portal

Researchers at the National Centre for Human Genome Studies and Research (NCHGSR) Panjab University have reported the anti-cancer potential of an anti-parasitic agent Fenbendazole. The anti-parasitic agent acts through moderate microtubule disruption, p53 stabilization and interference with glucose metabolism leading to preferential elimination of cancer cells both in vitro and in vivo. Based on the pre-clinical data from the toxicological studies performed on animals, Fenbendazole can be considered as an ideal candidate for exploring repurposing potential in cancer therapy.


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Repurposing the potential of photodynamic therapy drugs in pancreatic cancer

August 23rd 2018, Posted by: Drug Repurposing Portal

Loss of p53 function by mutations is one of the most common genetic perturbation associated with cancers. Two drugs used in photodynamic therapy, protoporphyrin IX (PpIX) and benzoporphyrin derivative monoacid ring A (BPD, verteporfin), were found to activate "Transcriptionally Active" (TA) p73 and induce apoptosis in pancreatic cancer cells. TAp73 can make up for the loss of p53 function and inhibit the evasion of cell death by cancer cells. These drugs can also inhibit antioxidant defense enzyme, thioredoxin reductase 1 and increase reactive oxygen species further contributing to cell death in pancreatic cancer cells. Thus, the repurposing of these photodynamic therapy drugs holds promise for therapeutic management of pancreatic cancer.


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Beta-blocker carvedilol repositioning as a Novel Autophagy Inducer

August 22nd 2018, Posted by: Drug Repurposing Portal

Aberrant activation of NLRP3 is implicated in the pathogenesis of inflammatory diseases. Carvedilol (CVL) an alpha-, beta-blocker is approved for treating congestive heart failure and high blood pressure. Additional clinical benefits of CVL include potential anti-inflammatory activity. Researchers from National Defense Medical Center, Taiwan, verified that CVL is a novel autophagy inducer that inhibited the NLRP3 inflammasome and suggested the prospective repositioning of CVL for ameliorating NLRP3-associated complications.


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Repurposing the schizophrenia drug Thioridazine Hydrochloride (TDZ) as an anti-inflammatory agent

August 20th 2018, Posted by: Drug Repurposing Portal

Thioridazine (Mellaril or Melleril) is a anti-psychotic drug which was previously to treat schizophrenia and psychosis. The branded product was withdrawn worldwide in 2005 because it caused severe cardiac arrhythmias. A recent study published in Science Reports used a computer aided drug identification protocol and identified that Thioridazine (TDZ) has a potential to be repurposed for treating inflammation. TDZ blocks the activation of NF-?B which is a potent mediator of inflammation.


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Approved drug for Parkinson's disease repurposed for Duchenne Muscular Dystrophy

August 14th 2018, Posted by: Drug Repurposing Portal

A recent pre-clinical study published in Frontiers in Physiology has reported that Safinamide, approved as an adjunctive treatment to levodopa/carbidopa in patients with Parkinson?s disease (PD), has the potential to be repurposed for Duchenne Muscular Dystrophy (DMD). Mitochondrial enzyme monoamine oxidase (MAO) is a relevant source of reactive oxygen species (ROS) not only in murine models of muscular dystrophy, in which it directly contributes to contractile impairment, but also in muscle cells from collagen VI-deficient patients. Safinamide, a monoamine oxidase type B (MAO-B) inhibitor was found to be efficacious in both in vivo and in vitro models of DMD.


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Drug Repurposing for Duchenne Muscular Dystrophy: The Monoamine Oxidase B Inhibitor Safinamide Ameliorates the Pathological Phenotype in mdx Mice and in Myogenic Cultures From DMD Patients

August 14th 2018, Posted by: Drug Repurposing Portal

Mitochondrial monoamine oxidases (MAOs) are significant sources of reactive oxygen species (ROS) in murine models of muscular dystrophy and in muscle cells of collagen VI-deficient patients. A new study discusses the potential of safinamide, a novel MAO-B inhibitor, in murine models of Duchenne muscular dystrophy (DMD). Administration of safinamide to mdx mice reduced myofiber damage and oxidative stress and improved muscle functionality. Since safinamide is clinically used to treat neurological disorders, the current study paves the way for potentially repurposing safinamide in DMD patients.


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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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Microtubule stabilizing drugs repositioned for central nervous system disorders

August 8th 2018, Posted by: Drug Repurposing Portal

One of the most clinically useful chemotherapeutic drugs are microtubule stabilizing agents, which normally stabilize microtubules and inhibit cell division. A recent study has found that a new generation of these compounds displayed improved PK properties and brain penetrance, with minimal side effects. Several brain disorders are intrinsically associated with microtubule defects and efforts to reposition microtubule-targeting chemotherapeutic agents for treating CNS, neurodegenerative, and psychiatric disorders are underway.


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An integrated web portal for drug discovery and drug repurposing in diabetes

August 6th 2018, Posted by: Drug Repurposing Portal

Molecular Property Diagnostic Suite - Diabetes Mellitus (MPDSDM) is a disease-specific web portal for diabetes with an objective to have open source data repository that contains all the information on diabetes. This portal comprises of 3 modules namely i) data library: ii) data processing and iii) data analysis tools. Extensive and curated information about diabetes-associated genes as well as drugs, targets, biomarkers, druggability, pathways etc. are included in the data library module. This information can be used for developing therapeutics to cure diabetes via conventional and drug repurposing approaches. Furthermore, virtual screening of 1455 FDA approved drugs on selected 20 diabetes associated targets was performed using docking protocol and their biological activity was predicted using "PASS Online" server. In this way, 5 drugs (which are earlier known for anti-malarial/microbial, anti-viral, anti-cancer, anti-pulmonary activities) were proposed to have repurposing potential for type 2 diabetes.


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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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