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Repurposing drugs

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https://www.readbyqxmd.com/read/28088112/a-current-perspective-on-the-oncopreventive-and-oncolytic-properties-of-selective-serotonin-reuptake-inhibitors
#1
REVIEW
Daniel P Radin, Parth Patel
Current cancer research strongly focuses on identifying novel pathways that can be selectively exploited in the clinic and identifying drugs capable of exploiting cancer vulnerabilities. Occasionally, drugs identified to exploit a cancer-specific vulnerability are on the market for clinical indications in another disease area. Rebranding them as anti-cancer drugs is a process commonly referred to as drug repurposing and is typically a faster method than bringing a novel drug to market. Selective serotonin reuptake inhibitors (SSRIs) are primarily used for treating several types of depression, but over the past two decades mounting evidence suggests that drugs in this class have oncolytic properties and reduce the risk of certain cancers...
January 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28078787/targeting-nasopharyngeal-carcinoma-by-artesunate-through-inhibiting-akt-mtor-and-inducing-oxidative-stress
#2
Qin Li, Wei Ni, Zhifeng Deng, Minghe Liu, Lazhi She, Qiong Xie
Drug repurposing has become an alternative therapeutic strategy for cancer treatment given the known pharmacokinetics and toxicity. The inhibitory effects of artesunate have been reported in various cancers. In this work, we investigated the effects of artesunate in nasopharyngeal carcinoma (NPC). We demonstrate that artesunate significantly inhibits proliferation via arresting NPC cells at G2/M phase. It also induces apoptosis through caspase-dependent and mitochondria-independent pathways in multiple NPC cell lines...
January 11, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28076436/correction-a-network-based-data-integration-approach-to-support-drug-repurposing-and-multi-target-therapies-in-triple-negative-breast-cancer
#3
Francesca Vitali, Laurie D Cohen, Andrea Demartini, Angela Amato, Vincenzo Eterno, Alberto Zambelli, Riccardo Bellazzi
[This corrects the article DOI: 10.1371/journal.pone.0162407.].
2017: PloS One
https://www.readbyqxmd.com/read/28075449/construction-of-an-mirna-regulated-drug-pathway-network-reveals-drug-repurposing-candidates-for-myasthenia-gravis
#4
Yuze Cao, Xiaoyan Lu, Jianjian Wang, Huixue Zhang, Zhaojun Liu, Si Xu, Tianfeng Wang, Shangwei Ning, Bo Xiao, Lihua Wang
Myasthenia gravis (MG) is a rare debilitating autoimmune neuromuscular disorder. Many studies have focused on the mechanism and treatment strategies of MG. However, the exact pathogenesis of MG and effective treatment strategies remain unclear. Recent studies have indicated that microRNAs (miRNAs or miRs) can regulate the pathological pathways of MG, suggesting their potential role in novel treatments. In the present study, we created a comprehensive catalog of experimentally confirmed MG risk genes and miRNAs by manually mining published literature and public databases...
January 11, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28073970/estimated-generic-prices-for-novel-treatments-for-drug-resistant-tuberculosis
#5
Dzintars Gotham, Joseph Fortunak, Anton Pozniak, Saye Khoo, Graham Cooke, Frederick E Nytko, Andrew Hill
BACKGROUND: The estimated worldwide annual incidence of MDR-TB is 480 000, representing 5% of TB incidence, but 20% of mortality. Multiple drugs have recently been developed or repurposed for the treatment of MDR-TB. Currently, treatment for MDR-TB costs thousands of dollars per course. OBJECTIVES: To estimate generic prices for novel TB drugs that would be achievable given large-scale competitive manufacture. METHODS: Prices for linezolid, moxifloxacin and clofazimine were estimated based on per-kilogram prices of the active pharmaceutical ingredient (API)...
January 10, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28068604/2-8-bis-trifluoromethyl-quinoline-analogs-show-improved-anti-zika-virus-activity-compared-to-mefloquine
#6
Giselle Barbosa-Lima, Adriana M Moraes, Adriele da S Araújo, Emerson T da Silva, Caroline S de Freitas, Yasmine R Vieira, Andressa Marttorelli, José Cerbino Neto, Patrícia T Bozza, Marcus V N de Souza, Thiago Moreno L Souza
Zika virus (ZIKV), an arthropod-born Flavivirus, has been associated with a wide range of neurological diseases in adults, foetuses and neonates. Since no vaccine is available, repurposing of antiviral drugs currently in medical use is necessary. Mefloquine has confirmed anti-ZIKV activity. We used medicinal chemistry-driven approaches to synthesize and evaluate the ability of a series of new 2,8-bis(trifluoromethyl)quinoline derivatives to inhibit ZIKV replication in vitro, in order to improve the potency of mefloquine...
December 30, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28067623/seizure-control-through-genetic-and-pharmacological-manipulation-of-pumilio-a-key-component-of-neuronal-homeostasis
#7
Wei-Hsiang Lin, Carlo N G Giachello, Richard A Baines
Epilepsy is a significant disorder for which approximately one-third of patients do not respond to drug treatments. Next-generation drugs, which interact with novel targets, are required to provide a better clinical outcome for these individuals. To identify potential novel targets for antiepileptic drug (AED) design, we used RNA sequencing to identify changes in gene transcription in two seizure models of the fruitfly Drosophila melanogaster The first model compared gene transcription between wildtype (WT) and the bangsenseless(1) (para(bss)) mutant; a gain-of-function in the sole fly voltage-gated sodium channel (paralytic)...
December 14, 2016: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28063067/dockingapp-a-user-friendly-interface-for-facilitated-docking-simulations-with-autodock-vina
#8
Elena Di Muzio, Daniele Toti, Fabio Polticelli
Molecular docking is a powerful technique that helps uncover the structural and energetic bases of the interaction between macromolecules and substrates, endogenous and exogenous ligands, and inhibitors. Moreover, this technique plays a pivotal role in accelerating the screening of large libraries of compounds for drug development purposes. The need to promote community-driven drug development efforts, especially as far as neglected diseases are concerned, calls for user-friendly tools to allow non-expert users to exploit the full potential of molecular docking...
January 6, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28060329/drug-repurposing-hypothesis-generation-using-the-re-fine-drugs-system
#9
Kelly Regan, Soheil Moosavinasab, Philip Payne, Simon Lin
The promise of drug repurposing is that existing drugs may be used for new disease indications in order to curb the high costs and time for approval. The goal of computational methods for drug repurposing is to enable solutions for safer, cheaper and faster drug discovery. Towards this end, we developed a novel method that integrates genetic and clinical phenotype data from large-scale GWAS and PheWAS studies with detailed drug information on the concept of transitive Drug-Gene-Disease triads. We created "RE:fine Drugs," a freely available, interactive dashboard that automates gene, disease and drug-based searches to identify drug repurposing candidates...
December 11, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28057171/predicting-high-impact-pharmacological-targets-by-integrating-transcriptome-and-text-mining-features
#10
Anatoly Mayburd, Ancha Baranova
PURPOSE: Novel, "outside of the box" approaches are needed for evaluating candidate molecules, especially in oncology. Throughout the years of 2000-2010, the efficiency of drug development fell to barely acceptable levels, and in the second decade of this century, levels have improved only marginally. This dismal condition continues despite unprecedented progress in the development of a variety of high-throughput tools, computational methods, aggregated databases, drug repurposing programs and innovative chemistries...
October 2016: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28053048/identifying-new-antiepileptic-drugs-through-genomics-based-drug-repurposing
#11
Nasir Mirza, Greame J Sills, Munir Pirmohamed, Anthony G Marson
Currently available antiepileptic drugs (AEDs) fail to control seizures in 30% of patients. Genomics-based drug repurposing (GBR) offers the potential of savings in the time and cost of developing new AEDs. In the current study, we used published data and software to identify the transcriptomic signature of chornic temporal lobe epilepsy and the drugs that reverse it. After filtering out compounds based on exclusion criteria, such as toxicity, 36 drugs were retained. 11 of the 36 drugs identified (>30%) have published evidence of antiepileptic efficacy (for example, curcumin) or antiepileptogenic affect (for example, atorvastatin) in recognised rodent models or patients...
January 4, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28052010/a-screen-for-fli-1-transcriptional-modulators-identifies-pkc-agonists-that-induce-erythroid-to-megakaryocytic-differentiation-and-suppress-leukemogenesis
#12
Tangjingjun Liu, Yao Yao, Gang Zhang, Ye Wang, Bin Deng, Jialei Song, Xiaogang Li, Fei Han, Xiao Xiao, Jue Yang, Lei Xia, You-Jun Li, Maksym Plachynta, Mu Zhang, Chen Yan, Shuzhen Mu, Heng Luo, Eldad Zacksenhaus, Xiaojiang Hao, Yaacov Ben-David
The ETS-related transcription factor Fli-1 affects many developmental programs including erythroid and megakaryocytic differentiation, and is frequently de-regulated in cancer. Fli-1 was initially isolated following retrovirus insertional mutagenesis screens for leukemic initiator genes, and accordingly, inhibition of this transcription factor can suppress leukemia through induction of erythroid differentiation. To search for modulators of Fli-1, we hereby performed repurposing drug screens with compounds isolated from Chinese medicinal plants...
December 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/28051114/novel-therapeutics-identification-for-fibrosis-in-renal-allograft-using-integrative-informatics-approach
#13
Li Li, Ilana Greene, Benjamin Readhead, Madhav C Menon, Brian A Kidd, Andrew V Uzilov, Chengguo Wei, Nimrod Philippe, Bernd Schroppel, John Cijiang He, Rong Chen, Joel T Dudley, Barbara Murphy
Chronic allograft damage, defined by interstitial fibrosis and tubular atrophy (IF/TA), is a leading cause of allograft failure. Few effective therapeutic options are available to prevent the progression of IF/TA. We applied a meta-analysis approach on IF/TA molecular datasets in Gene Expression Omnibus to identify a robust 85-gene signature, which was used for computational drug repurposing analysis. Among the top ranked compounds predicted to be therapeutic for IF/TA were azathioprine, a drug to prevent acute rejection in renal transplantation, and kaempferol and esculetin, two drugs not previously described to have efficacy for IF/TA...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28045897/correction-large-scale-off-target-identification-using-fast-and-accurate-dual-regularized-one-class-collaborative-filtering-and-its-application-to-drug-repurposing
#14
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pcbi.1005135.].
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28042066/repurposing-medications-for-hospice-palliative-care-symptom-control-is-no-longer-sufficient-a-manifesto-for-change
#15
David C Currow, Amy P Abernethy, Marie Fallon, Russell K Portenoy
The World Health Organisation (WHO) essential medications list for hospice / palliative care reflects that, with the judicious use of currently available medications, the majority of symptoms can be lessened, and some controlled completely. Even with optimal use of current medications, symptom control is still unacceptable for many people. Currently available medications offer great benefit to a minority of patients, some benefit to an additional group, and no benefit or harms to others. In symptom control, development of new drugs is advancing at a glacial pace, contrasting to the rapid advances seen in many other disciplines...
December 29, 2016: Journal of Pain and Symptom Management
https://www.readbyqxmd.com/read/28038466/drug-dependent-functionalization-of-wild-type-and-mutant-p53-in-cisplatin-resistant-human-ovarian-tumor-cells
#16
Michelle Bhatt, Cristina Ivan, Xiaolei Xie, Zahid H Siddik
Cisplatin (cis-Pt) resistance in tumor cells from p53 dysfunction is a significant clinical problem. Although mutation can inhibit p53 function, >60% of p53 mutants retain normal function according to literature reports. Therefore, we examined the status of p53 in cisplatin-resistant ovarian tumor models and its functional response to cis-Pt and the mechanistically-distinct non-cross-resistant oxaliplatin (oxali-Pt). Relative to sensitive A2780 cells harboring wild-type p53, the 2780CP/Cl-16, OVCAR-10, Hey and OVCA-433 cell lines were 10- to 30-fold resistant to cis-Pt, but was substantially circumvented by oxali-Pt...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28035920/using-drugs-as-molecular-probes-a%C3%A2-computational-chemical-biology-approach-in-neurodegenerative-diseases
#17
Mohammad Asif Emran Khan Emon, Alpha Tom Kodamullil, Reagon Karki, Erfan Younesi, Martin Hofmann-Apitius
Neurodegenerative diseases including Alzheimer's disease are complex to tackle because of the complexity of the brain, both in structure and function. Such complexity is reflected by the involvement of various brain regions and multiple pathways in the etiology of neurodegenerative diseases that render single drug target approaches ineffective. Particularly in the area of neurodegeneration, attention has been drawn to repurposing existing drugs with proven efficacy and safety profiles. However, there is a lack of systematic analysis of the brain chemical space to predict the feasibility of repurposing strategies...
December 30, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28025934/drug-repurposing-in-anticancer-reagent-development
#18
Peng-Chen Chen, Xaiolong Liu, Yao Lin
The development process for cancer drugs is risky, lengthy and costly. Exploration of the anticancer potential of listed non-cancer drugs has become a popular research field in the pharmaceutical industry. The efficacy of various drugs are tested in multiple cancer types and the mechanisms underlying their effect were investigated. In this review, we have summarized the drug relocation instances for different cancer types in recent years and discussed the future direction of drug repurposing.
December 26, 2016: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28025347/hedd-the-human-epigenetic-drug-database
#19
Yunfeng Qi, Dadong Wang, Daying Wang, Taicheng Jin, Liping Yang, Hui Wu, Yaoyao Li, Jing Zhao, Fengping Du, Mingxia Song, Renjun Wang
Epigenetic drugs are chemical compounds that target disordered post-translational modification of histone proteins and DNA through enzymes, and the recognition of these changes by adaptor proteins. Epigenetic drug-related experimental data such as gene expression probed by high-throughput sequencing, co-crystal structure probed by X-RAY diffraction and binding constants probed by bio-assay have become widely available. The mining and integration of multiple kinds of data can be beneficial to drug discovery and drug repurposing...
2016: Database: the Journal of Biological Databases and Curation
https://www.readbyqxmd.com/read/28018344/adjunct-strategies-for-tuberculosis-vaccines-modulating-key-immune-cell-regulatory-mechanisms-to-potentiate-vaccination
#20
REVIEW
Lakshmi Jayashankar, Richard Hafner
Tuberculosis (TB) remains a global health threat of alarming proportions, resulting in 1.5 million deaths worldwide. The only available licensed vaccine, Bacillus Calmette-Guérin, does not confer lifelong protection against active TB. To date, development of an effective vaccine against TB has proven to be elusive, and devising newer approaches for improved vaccination outcomes is an essential goal. Insights gained over the last several years have revealed multiple mechanisms of immune manipulation by Mycobacterium tuberculosis (Mtb) in infected macrophages and dendritic cells that support disease progression and block development of protective immunity...
2016: Frontiers in Immunology
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