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Drug repurposing

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https://www.readbyqxmd.com/read/29765977/systems-pharmacology-based-approach-of-connecting-disease-genes-in-genome-wide-association-studies-with-traditional-chinese-medicine
#1
Jihye Kim, Minjae Yoo, Jimin Shin, Hyunmin Kim, Jaewoo Kang, Aik Choon Tan
Traditional Chinese medicine (TCM) originated in ancient China has been practiced over thousands of years for treating various symptoms and diseases. However, the molecular mechanisms of TCM in treating these diseases remain unknown. In this study, we employ a systems pharmacology-based approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. We studied 102 TCM components and their target genes by analyzing microarray gene expression experiments. We constructed disease-gene networks from 2558 GWAS studies...
2018: International Journal of Genomics
https://www.readbyqxmd.com/read/29765555/a-protein-folding-molecular-imaging-biosensor-monitors-the-effects-of-drugs-that-restore-mutant-p53-structure-and-its-downstream-function-in-glioblastoma-cells
#2
Ramasamy Paulmurugan, Rayhaneh Afjei, Thillai V Sekar, Husam A Babikir, Tarik F Massoud
Misfolding mutations in the DNA-binding domain of p53 alter its conformation, affecting the efficiency with which it binds to chromatin to regulate target gene expression and cell cycle checkpoint functions in many cancers, including glioblastoma. Small molecule drugs that recover misfolded p53 structure and function may improve chemotherapy by activating p53-mediated senescence. We constructed and optimized a split Renilla luciferase (RLUC) complementation molecular biosensor (NRLUC-p53-CRLUC) to determine small molecule-meditated folding changes in p53 protein...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29764454/screening-a-repurposing-library-the-medicines-for-malaria-venture-stasis-box-against-schistosoma-mansoni
#3
Valérian Pasche, Benoît Laleu, Jennifer Keiser
BACKGROUND: The development of new treatments against schistosomiasis is imperative but lacks commercial interest. Drug repurposing represents a suitable strategy to identify potential treatments, which have already unblocked several essential steps along the drug development path, hence reducing costs and timelines. Promoting this approach, the Medicines for Malaria Venture (MMV) recently distributed a drug repurposing library of 400 advanced lead candidates (Stasis Box). METHODS: All 400 compounds were initially tested in vitro against the larval stage of Schistosoma mansoni at 10 μM...
May 15, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29763317/chemoproteomic-profiling-reveals-ethacrynic-acid-targets-adenine-nucleotide-translocases-to-impair-mitochondrial-function
#4
Zi Ye, Xiaoyun Zhang, Yuangang Zhu, Tong Song, Xiaowei Chen, Xiaoguang Lei, Chu Wang
Ethacrynic acid (EA) is a diuretic drug that is widely used to treat high-blood pressure and swelling caused by congestive heart failure or kidney failure. It acts through noncovalent inhibition of the Na+ -K+ -2Cl- cotransporter in the thick ascending limb of Henle's loop. Chemically, EA contains a Michael acceptor group that can react covalently with nucleophilic residues in proteins; however, the proteome reactivity of EA remains unexplored. Herein, we took a quantitative chemoproteomic approach to globally profile EA's targets in cancer cells...
May 15, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29762783/repurposing-the-anthelminthic-salicylanilide-oxyclozanide-against-susceptible-and-clinical-resistant-candida-albicans-strains
#5
Emilie Pic, Anaïs Burgain, Adnane Sellam
Current antifungal drugs suffer from limitations including toxicity, adverse interactions with other commonly prescribed drugs, and the emergence of resistant strains. Here, we repurposed the anthelmintic oxyclozanide as a potent antifungal agent against both sensitive and resistant clinical isolates of Candida albicans, as well as other human opportunistic fungi. Antifungal activity of oxyclozanide was enhanced when C. albicans grew in nonfermentable carbon sources. Our data support a mechanism of action where oxyclozanide uncoupled the mitochondrial electron transport from oxidative phosphorylation and perturbed the mitochondrial membrane potential...
May 14, 2018: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/29760790/anticancer-properties-of-fenofibrate-a-repurposing-use
#6
REVIEW
Xin Lian, Gang Wang, Honglan Zhou, Zongyu Zheng, Yaowen Fu, Lu Cai
Cancer is a leading cause of death throughout the world, and cancer therapy remains a big medical challenge in terms of both its therapeutic efficacy and safety. Therefore, to find out a safe anticancer drug has been long goal for oncologist and medical scientists. Among clinically used medicines with no or little toxicity, fenofibrate is a drug of the fibrate class that plays an important role in lowering the levels of serum cholesterol and triglycerides while elevating the levels of high-density lipoproteins...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29760165/the-impact-of-transcription-on-metabolism-in-prostate-and-breast-cancers
#7
Ninu Poulose, Ian G Mills, Rebecca E Steele
Metabolic dysregulation is regarded as an important driver in cancer development and progression. The impact of transcriptional changes on metabolism have been intensively studied in hormone-dependent cancers, and in particular in prostate and breast cancer. These cancers have strong similarities in the function of important transcriptional drivers, such as the estrogen and androgen receptor, at the level of dietary risk and epidemiology, genetics and therapeutically. In this review we will focus on the function of these nuclear hormone receptors and their downstream impact on metabolism, with a particular focus on lipid metabolism...
May 14, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29759926/drug-repurposing-for-viral-infectious-diseases-how-far-are-we
#8
REVIEW
Beatrice Mercorelli, Giorgio Palù, Arianna Loregian
Despite the recent advances in controlling some viral pathogens, most viral infections still lack specific treatment. Indeed, the need for effective therapeutic strategies to combat 'old', emergent, and re-emergent viruses is not paralleled by the approval of new antivirals. In the past years, drug repurposing combined with innovative approaches for drug validation, and with appropriate animal models, significantly contributed to the identification of new antiviral molecules and targets for therapeutic intervention...
May 11, 2018: Trends in Microbiology
https://www.readbyqxmd.com/read/29758010/combined-transcriptomics-proteomics-and-bioinformatics-identify-drug-targets-in-spinal-cord-injury
#9
Jure Tica, Elizabeth J Bradbury, Athanasios Didangelos
Spinal cord injury (SCI) causes irreversible tissue damage and severe loss of neurological function. Currently, there are no approved treatments and very few therapeutic targets are under investigation. Here, we combined 4 high-throughput transcriptomics and proteomics datasets, 7 days and 8 weeks following clinically-relevant rat SCI to identify proteins with persistent differential expression post-injury. Out of thousands of differentially regulated entities our combined analysis identified 40 significantly upregulated versus 48 significantly downregulated molecules, which were persistently altered at the mRNA and protein level, 7 days and 8 weeks post-SCI...
May 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29753658/feasibility-and-biological-rationale-of-repurposing-sunitinib-and-erlotinib-for-dengue-treatment
#10
Szuyuan Pu, Fei Xiao, Stanford Schor, Elena Bekerman, Fabio Zanini, Rina Barouch-Bentov, Claude M Nagamine, Shirit Einav
There is an urgent need for strategies to combat dengue virus (DENV) infection; a major global threat. We reported that the cellular kinases AAK1 and GAK regulate intracellular trafficking of multiple viruses and that sunitinib and erlotinib, approved anticancer drugs with potent activity against these kinases, protect DENV-infected mice from mortality. Nevertheless, further characterization of the therapeutic potential and underlying mechanism of this approach is required prior to clinical evaluation. Here, we demonstrate that sunitinib/erlotinib combination achieves sustained suppression of systemic infection at approved dose in DENV-infected IFN-α/β and IFN-γ receptor-deficient mice...
May 10, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29753379/the-antiarrhythmic-drug-amiodarone-decreases-akt-activity-and-sensitizes-human-acute-myeloid-leukemia-cells-to-apoptosis-by-abt-263
#11
Corey J Ketchem, Cory Kucera, Aditya Barve, Levi J Beverly
BACKGROUND: Successful treatment of leukemia requires new medications to combat drug resistance, but the development of novel therapies is an arduous and risky endeavor. Repurposing currently approved drugs or those already in clinical development to treat other indications is a more practical approach. Moreover, combinatorial therapeutics are often more efficacious than single agent therapeutics because the former can simultaneously target multiple pathways that mitigate tumor aggressiveness and induce cancer cell death...
May 2018: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/29751602/old-drugs-as-new-treatments-for-neurodegenerative-diseases
#12
REVIEW
Fernando Durães, Madalena Pinto, Emília Sousa
Neurodegenerative diseases are increasing in number, given that the general global population is becoming older. They manifest themselves through mechanisms that are not fully understood, in many cases, and impair memory, cognition and movement. Currently, no neurodegenerative disease is curable, and the treatments available only manage the symptoms or halt the progression of the disease. Therefore, there is an urgent need for new treatments for this kind of disease, since the World Health Organization has predicted that neurodegenerative diseases affecting motor function will become the second-most prevalent cause of death in the next 20 years...
May 11, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29751486/current-strategies-for-inhibition-of-chikungunya-infection
#13
REVIEW
Bharat Bhusan Subudhi, Soma Chattopadhyay, Priyadarsee Mishra, Abhishek Kumar
Increasing incidences of Chikungunya virus (CHIKV) infection and co-infections with Dengue/Zika virus have highlighted the urgency for CHIKV management. Failure in developing effective vaccines or specific antivirals has fuelled further research. This review discusses updated strategies of CHIKV inhibition and provides possible future directions. In addition, it analyzes advances in CHIKV lifecycle, drug-target development, and potential hits obtained by in silico and experimental methods. Molecules identified with anti-CHIKV properties using traditional/rational drug design and their potential to succeed in subsequent stages of drug development have also been discussed...
May 3, 2018: Viruses
https://www.readbyqxmd.com/read/29751356/exploring-novel-pharmacotherapeutic-applications-and-repurposing-potential-of-sodium-glucose-cotransporter-2-sglt2-inhibitors
#14
REVIEW
Tushar Madaan, Ibraheem Husain, Mohamad Akhtar, Abul Kalam Najmi
Sodium glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of anti-hyperglycemic drugs with a distinctive mechanism of action focusing on renal absorption ofglucose. Apart from its anti-hyperglycemic effects, a multitude of research studies on this classhave revealed that these drugs have far more versatile and comprehensive pharmacologicaleffects than previously believed. Approximately 30% of FDA approved drugs are repurposedand used for indications other than those they were initially intended for...
May 11, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29746793/high-throughput-flow-cytometry-identifies-small-molecule-inhibitors-for-drug-repurposing-in-t-all
#15
Dominique R Perez, Christian K Nickl, Anna Waller, Cristina Delgado-Martin, Travis Woods, Nitesh D Sharma, Michelle L Hermiston, Mignon L Loh, Stephen P Hunger, Stuart S Winter, Alexandre Chigaev, Bruce Edwards, Larry A Sklar, Ksenia Matlawska-Wasowska
Kinase inhibitors have dramatically increased patient survival in a multitude of cancers, including hematological malignancies. However, kinase inhibitors have not yet been integrated into current clinical trials for patients with T-cell-lineage acute lymphoblastic leukemia (T-ALL). In this study, we used a high-throughput flow cytometry (HTFC) approach to test a collection of small-molecule inhibitors, including 26 FDA-approved tyrosine kinase inhibitors in a panel of T-ALL cell lines and patient-derived xenografts...
May 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29743944/repurposing-drugs-in-oncology-redo-selective-pde5-inhibitors-as-anti-cancer-agents
#16
Pan Pantziarka, Vidula Sukhatme, Sergio Crispino, Gauthier Bouche, Lydie Meheus, Vikas P Sukhatme
Selective phosphodiesterase 5 inhibitors, including sildenafil, tadalafil and vardenafil, are widely-used in the treatment of erectile dysfunction and pulmonary arterial hypertension. They are also well-known as examples of successful drug repurposing in that they were initially developed for angina and only later developed for erectile dysfunction. However, these drugs may also be effective cancer treatments. A range of evidentiary sources are assessed in this paper and the case made that there is pre-clinical and clinical evidence that these drugs may offer clinical benefit in a range of cancers...
2018: Ecancermedicalscience
https://www.readbyqxmd.com/read/29743517/identification-of-new-epha4-inhibitors-by-virtual-screening-of-fda-approved-drugs
#17
Shuo Gu, Wing-Yu Fu, Amy K Y Fu, Estella Pui Sze Tong, Fanny C F Ip, Xuhui Huang, Nancy Y Ip
The receptor tyrosine kinase, erythropoietin-producing hepatocellular A4 (EphA4), was recently identified as a molecular target for Alzheimer's disease (AD). We found that blockade of the interaction of the receptor and its ligands, ephrins, alleviates the disease phenotype in an AD transgenic mouse model, suggesting that targeting EphA4 is a potential approach for developing AD interventions. In this study, we identified five FDA-approved drugs-ergoloid, cyproheptadine, nilotinib, abiraterone, and retapamulin-as potential inhibitors of EphA4 by using an integrated approach combining virtual screening with biochemical and cellular assays...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29741655/cooperative-recognition-of-t-t-mismatch-by-echinomycin-causes-structural-distortions-in-dna-duplex
#18
Pei-Ching Wu, Shu-Ling Tzeng, Chung-Ke Chang, Ya-Fen Kao, Michael J Waring, Ming-Hon Hou
Small-molecule compounds that target mismatched base pairs in DNA offer a novel prospective for cancer diagnosis and therapy. The potent anticancer antibiotic echinomycin functions by intercalating into DNA at CpG sites. Surprisingly, we found that the drug strongly prefers to bind to consecutive CpG steps separated by a single T:T mismatch. The preference appears to result from enhanced cooperativity associated with the binding of the second echinomycin molecule. Crystallographic studies reveal that this preference originates from the staggered quinoxaline rings of the two neighboring antibiotic molecules that surround the T:T mismatch forming continuous stacking interactions within the duplex...
May 8, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29740519/repurposing-drugs-to-fast-track-therapeutic-agents-for-the-treatment-of-cryptococcosis
#19
Megan Truong, Leigh G Monahan, Dee A Carter, Ian G Charles
Many infectious diseases disproportionately affect people in the developing world. Cryptococcal meningitis is one of the most common mycoses in HIV-AIDS patients, with the highest burden of disease in sub-Saharan Africa. Current best treatment regimens still result in unacceptably high mortality rates, and more effective antifungal agents are needed urgently. Drug development is hampered by the difficulty of developing effective antifungal agents that are not also toxic to human cells, and by a reluctance among pharmaceutical companies to invest in drugs that cannot guarantee a high financial return...
2018: PeerJ
https://www.readbyqxmd.com/read/29737455/current-and-future-use-of-chloroquine-and-hydroxychloroquine-in-infectious-immune-neoplastic-and-neurological-diseases-a-mini-review
#20
REVIEW
Domenico Plantone, Tatiana Koudriavtseva
The process of finding new therapeutic indications for currently used drugs, defined as 'repurposing', is receiving growing attention. Chloroquine and hydroxychloroquine, with an original indication to prevent or cure malaria, have been successfully used to treat several infectious (HIV, Q fever, Whipple's disease, fungal infections), rheumatological (systemic lupus erythematosus, antiphospholipid antibody syndrome, rheumatoid arthritis, Sjögren's syndrome), and other immunological diseases. Indeed, they have anti-inflammatory, immunomodulating, anti-infective, antithrombotic, and metabolic effects...
May 8, 2018: Clinical Drug Investigation
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