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Drug repurposing

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https://www.readbyqxmd.com/read/29331709/what-do-the-genetic-association-data-say-about-the-high-risk-of-suicide-in-people-with-depression-a-novel-network-based-approach-to-find-common-molecular-basis-for-depression-and-suicidal-behavior-and-related-therapeutic-targets
#1
Ali Bozorgmehr, Fatemeh Alizadeh, Sattar Norouzi Ofogh, Mohammad Reza Abdollahzadeh Hamzekalayi, Sara Herati, Atefeh Moradkhani, Ali Shahbazi, Mohammad Ghadirivasfi
BACKGROUND: Available sources indicate that the risk of suicide in people with major depression is higher than other psychiatric disorders. Although it seems that these two conditions may have a shared cause in some cases, no studies have been conducted to identify a common basis for them. METHODS: In this study, following an extensive review of literature, we found almost all the genes that are involved in major depression and suicidal behavior, and we isolated genes shared between the two conditions...
January 8, 2018: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29330123/a-bibliometric-review-of-drug-repurposing
#2
REVIEW
Nancy C Baker, Sean Ekins, Antony J Williams, Alexander Tropsha
We have conducted a bibliometric review of drug repurposing by scanning >25 million papers in PubMed and using text-mining methods to gather, count and analyze chemical-disease therapeutic relationships. We find that >60% of the ∼35 000 drugs or drug candidates identified in our study have been tried in more than one disease, including 189 drugs that have been tried in >300 diseases each. Whereas in the majority of cases these drugs were applied in therapeutic areas close to their original use, there have been striking, and perhaps instructive, successful attempts of drug repurposing for unexpected, novel therapeutic areas...
January 9, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29322935/classifying-cancer-genome-aberrations-by-their-mutually-exclusive-effects-on-transcription
#3
Jonathan B Dayton, Stephen R Piccolo
BACKGROUND: Malignant tumors are typically caused by a conglomeration of genomic aberrations-including point mutations, small insertions, small deletions, and large copy-number variations. In some cases, specific chemotherapies and targeted drug treatments are effective against tumors that harbor certain genomic aberrations. However, predictive aberrations (biomarkers) have not been identified for many tumor types and treatments. One way to address this problem is to examine the downstream, transcriptional effects of genomic aberrations and to identify characteristic patterns...
December 21, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/29322778/using-genome-sequence-to-enable-the-design-of-medicines-and-chemical-probes
#4
Alicia J Angelbello, Jonathan L Chen, Jessica L Childs-Disney, Peiyuan Zhang, Zi-Fu Wang, Matthew D Disney
Rapid progress in genome sequencing technology has put us firmly into a postgenomic era. A key challenge in biomedical research is harnessing genome sequence to fulfill the promise of personalized medicine. This Review describes how genome sequencing has enabled the identification of disease-causing biomolecules and how these data have been converted into chemical probes of function, preclinical lead modalities, and ultimately U.S. Food and Drug Administration (FDA)-approved drugs. In particular, we focus on the use of oligonucleotide-based modalities to target disease-causing RNAs; small molecules that target DNA, RNA, or protein; the rational repurposing of known therapeutic modalities; and the advantages of pharmacogenetics...
January 11, 2018: Chemical Reviews
https://www.readbyqxmd.com/read/29322257/repurposing-drugs-to-treat-neurological-diseases
#5
T H Massey, N P Robertson
No abstract text is available yet for this article.
January 10, 2018: Journal of Neurology
https://www.readbyqxmd.com/read/29321020/meta-analysis-of-human-gene-expression-in-response-to-mycobacterium-tuberculosis-infection-reveals-potential-therapeutic-targets
#6
Zhang Wang, Seda Arat, Michal Magid-Slav, James R Brown
BACKGROUND: With the global emergence of multi-drug resistant strains of Mycobacterium tuberculosis, new strategies to treat tuberculosis are urgently needed such as therapeutics targeting potential human host factors. RESULTS: Here we performed a statistical meta-analysis of human gene expression in response to both latent and active pulmonary tuberculosis infections from nine published datasets. We found 1655 genes that were significantly differentially expressed during active tuberculosis infection...
January 10, 2018: BMC Systems Biology
https://www.readbyqxmd.com/read/29315671/the-antimalarial-drug-amodiaquine-possesses-anti-zika-virus-activities
#7
Yingshan Han, Thibault Mesplède, Hongtao Xu, Yudong Quan, Mark A Wainberg
Zika virus (ZIKV) outbreak has emerged as a global health threat, particularly in tropical areas, over the past few years. No antiviral therapy or vaccine is available at present. For these reasons, repurposing clinically approved drugs against ZIKV infection may provide rapid and cost-effective global health benefits. Here we explored this strategy and screened eight FDA-approved drugs for antiviral activity against ZIKV using a cell-based assay. Our results show that the antimalarial drug amodiaquine has anti-ZIKV activity with EC50 at low micromolar concentrations in cell culture...
January 9, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29313889/inventing-new-therapies-without-reinventing-the-wheel-the-power-of-drug-repurposing
#8
EDITORIAL
Andreas Papapetropoulos, Csaba Szabo
This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc.
January 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29311239/induction-of-il-10-by-borrelia-burgdorferi-is-regulated-by-the-action-of-cd14-dependent-p38-mapk-and-camp-mediated-chromatin-remodeling
#9
Bikash Sahay, Kathleen Bashant, Nicole J Nelson, Rebeca L Patsey, Shiva Kumar Gadila, Rebecca Boohaker, Ashutosh Verma, Klemen Strle, Timothy J Sellati
Host genotype influences the severity of murine Lyme borreliosis, caused by the spirochetal bacterium Borrelia burgdorferi C57BL/6 (B6) mice develop mild, whereas C3H/HeN (C3H) mice develop severe Lyme arthritis. Differential expression of interleukin 10 (IL-10) has long been associated with mouse strain differences in Lyme pathogenesis; however, the underlying mechanism(s) of this genotype-specific IL-10 regulation remained elusive. Herein we reveal a cAMP-mediated mechanism of IL-10 regulation in B6 macrophages that is substantially diminished in C3H macrophages...
January 8, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29311092/pharmacodynamics-of-flubendazole-for-cryptococcal-meningoencephalitis-repurposing-and-reformulation-of-an-anti-parasitic-agent-for-a-neglected-fungal-disease
#10
Gemma L Nixon, Laura McEntee, Adam Johnson, Nikki Farrington, Sarah Whalley, Joanne Livermore, Cristien Natal, Gina Washbourn, Jaclyn Bibby, Neil Berry, Jodi Lestner, Megan Truong, Andrew Owen, David Lalloo, Ian Charles, William Hope
Current therapeutic options for cryptococcal meningitis are limited by toxicity, global supply and emergence of resistance. There is an urgent need to develop additional antifungal agents that are fungicidal within the central nervous system and preferably orally bioavailable. The benzimidazoles have broad-spectrum anti-parasitic activity, but also have in vitro antifungal activity that includes Cryptococcus neoformans Flubendazole (a benzimidazole) has been reformulated by Janssen Pharmaceutica as an amorphous solid drug nanodispersion to develop an orally bioavailable medicine for the treatment of neglected tropical diseases such as onchocerciasis...
January 8, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29311059/g-quadruplex-dna-motifs-in-the-malaria-parasite-plasmodium-falciparum-and-their-potential-as-novel-antimalarial-drug-targets
#11
Lynne M Harris, Katelyn R Monsell, Florian Noulin, M Toyin Famodimu, Nicolas Smargiasso, Christian Damblon, Paul Horrocks, Catherine J Merrick
G-quadruplexes are DNA or RNA secondary structures that can be formed from guanine-rich nucleic acids. These four-stranded structures, composed of stacked quartets of guanine bases, can be highly stable and have been demonstrated to occur in vivo in the DNA of human cells and other systems, where they play important biological roles, influencing processes such as telomere maintenance, DNA replication and transcription, or in the case of RNA G-quadruplexes, RNA translation and processing. We report for the first time that DNA G-quadruplexes can be detected in the nuclei of the malaria parasite Plasmodium falciparum, which has one of the most A/T-biased genomes sequenced and therefore possesses few guanine-rich sequences with the potential to form G-quadruplexes...
January 8, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29305880/distinct-effects-of-hiv-protease-inhibitors-and-erad-inhibitors-on-zygote-to-ookinete-transition-of-the-malaria-parasite
#12
Evi Goulielmaki, Sofia Kaforou, Kannan Venugopal, Thanasis G Loukeris, Inga Siden-Kiamos, Konstantinos Koussis
In an effort to eradicate malaria, new interventions are proposed to include compound/vaccine development against pre-erythrocytic, erythrocytic and mosquito stages of Plasmodium. Drug repurposing might be an alternative approach to new antimalarials reducing the cost and the time required for drug development. Previous in vitro studies have examined the effects of protease inhibitors on different stages of the Plasmodium parasite, although the clinical relevance of this remains unclear. In this study we tested the putative effect of three HIV protease inhibitors, two general aspartyl protease inhibitors and three AAA-p97 ATPase inhibitors on the zygote to ookinete transition of the Plasmodium parasite...
January 3, 2018: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/29301833/establishing-a-preclinical-multidisciplinary-board-for-brain-tumors
#13
Birgit Nimmervoll, Nidal Boulos, Brandon M Bianski, Jason Dapper, Michael DeCuypere, Anang A Shelat, Sabrina Terranova, Hope Elizabeth Terhune, Amar Gajjar, Yogesh T Patel, Burgess B Freeman, Arzu Onar-Thomas, Clinton F Stewart, Martine F Roussel, R Kiplin Guy, Thomas E Merchant, Christopher Calabrese, Karen D Wright, Richard J Gilbertson
PURPOSE: Curing all children with brain tumors will require an understanding of how each subtype responds to conventional treatments and how best to combine existing and novel therapies.  It is extremely challenging to acquire this knowledge in the clinic alone, especially among patients with rare tumors.  Therefore, we developed a preclinical brain tumor platform to test combinations of conventional and novel therapies in a manner that closely recapitulates clinic trials.  Experimental Design: A multidisciplinary team was established to design and conduct neurosurgical, fractionated radiotherapy and chemotherapy studies, alone or in combination, in accurate mouse models of supratentorial ependymoma (SEP) subtypes and choroid plexus carcinoma (CPC)...
January 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29300993/the-existing-drug-vorinostat-as-a-new-lead-against-cryptosporidiosis-by-targeting-the-parasite-histone-deacetylases
#14
Fengguang Guo, Haili Zhang, Nina N McNair, Jan R Mead, Guan Zhu
Background: Cryptosporidiosis affects all human populations, but can be much more severe or life-threatening in children and individuals with weak or weakened immune systems. However, current options to treat cryptosporidiosis are limited. Methods: An in vitro phenotypic screening assay was employed to screen 1,200 existing drugs for their anti-cryptosporidial activity, and to determine the inhibitory kinetics of top hits. Selected top hits were further evaluated in mice...
January 2, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29300762/drug-repurposing-in-vitro-anti-glycation-properties-of-18-common-drugs
#15
Saima Rasheed, Sara S Sánchez, Sammer Yousuf, Stella M Honoré, M Iqbal Choudhary
Drug repositioning or repurposing, i.e. identifying new indications for existing drugs, has gained increasing attention in the recent years. This approach enables the scientists to discover "new targets" for known drugs in a cost and time efficient manner. Glycation, the non-enzymatic reaction of sugars with proteins or nucleic acids to form early glycation (Amadori or fructosamine) products, is a key molecular basis of diabetic complications. Inhibiting the process of non-enzymatic protein glycation is one of the key strategies to prevent glycation-mediated diabetic complications...
2018: PloS One
https://www.readbyqxmd.com/read/29300482/chemotext-a-publicly-available-web-server-for-mining-drug-target-disease-relationships-in-pubmed
#16
Stephen Joseph Capuzzi, Thomas Thornton, Kammy Liu, Nancy Baker, Wai In Lam, Colin O'Banion, Eugene N Muratov, Diane Pozefsky, Alexander Tropsha
Elucidation of the mechanistic relationships between drugs, their targets, and diseases is at the core of modern drug discovery research. Thousands of studies relevant to the drug-target-disease (DTD) triangle have been published and annotated in the Medline/PubMed database. Mining this database affords rapid identification of all published studies that confirm connections between vertices of this triangle or enable new inferences of such connections. To this end, we describe the development of Chemotext, a publicly-available Web server that mines the entire compendium of published literature in PubMed annotated by Medline Subject Heading (MeSH) terms...
January 4, 2018: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29299939/repurposing-drugs-for-use-against-zika-virus-infection
#17
J Devillers
Zika virus (ZIKV) is a mosquito-borne flavivirus for which there are no vaccines or specific therapeutics. To find drugs active on the virus is a complex, expensive and time-consuming process. The prospect of drug repurposing, which consists of finding new indications for existing drugs, is an interesting alternative to expedite drug development for specific diseases. In theory, drug repurposing is also able to respond much more rapidly to a crisis than a classical drug discovery process. Consequently, the methodology is attractive for vector-borne diseases that can emerge or re-emerge worldwide with the risk to become pandemic quickly...
January 4, 2018: SAR and QSAR in Environmental Research
https://www.readbyqxmd.com/read/29298813/gpcrs-as-targets-for-approved-drugs-how-many-targets-and-how-many-drugs
#18
Krishna Sriram, Paul A Insel
Estimates vary regarding the number of G protein-coupled receptors, GPCRs, the largest family of membrane receptors that are targeted by approved drugs and the number of such drugs that target GPCRs. We review current knowledge regarding GPCRs as drug targets by integrating data from public databases (CHEMBL, IUPHAR and DRUGBANK) and from the Broad drug repurposing initiative. To account for discrepancies among these sources, we curated a list of GPCRs currently targeted by approved drugs. As of November, 2017, 134 GPCRs are targets for drugs approved in the United States or European Union; 128 GPCRs are targets for drugs listed in the FDA orange book...
January 3, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29298032/combating-intracellular-pathogens-with-repurposed-host-targeted-drugs
#19
Stanford Schor, Shirit Einav
There is a large, global unmet need for the development of countermeasures to combat intracellular pathogens. The development of novel antimicrobials is expensive and slow and typically focuses on selective inhibition of proteins encoded by a single pathogen, thereby providing a narrow spectrum of coverage. The repurposing of approved drugs targeting host functions required for microbial infections represents a promising alternative. This review summarizes progress and challenges in the repurposing of approved drugs as host-targeted broad-spectrum agents for the treatment of intracellular pathogens...
January 3, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29297423/meropenem-clavulanate-for-drug-resistant-tuberculosis-a-follow-up-of-relapse-free-cases
#20
M C Payen, I Muylle, O Vandenberg, V Mathys, M Delforge, S Van den Wijngaert, N Clumeck, S De Wit
BACKGROUND: Extensively drug-resistant tuberculosis (XDR-TB), defined as TB caused by a Mycobacterium strain resistant to at least rifampicin, isoniazid, any fluoroquinolone and one of the injectable anti-tuberculosis drugs, remains a worldwide public health threat. Among repurposed drugs empirically used for XDR-TB cases, carbapenems have been studied in vitro and in animal models, with encouraging results. However, only short-term follow-up data from clinical studies are currently available...
January 1, 2018: International Journal of Tuberculosis and Lung Disease
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