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Repurposing drugs

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https://www.readbyqxmd.com/read/29456622/does-the-oncology-community-have-a-rejection-bias-when-it-comes-to-repurposed-drugs
#1
EDITORIAL
Bishal Gyawali, Pan Pantziarka, Sergio Crispino, Gauthier Bouche
Among the various measures proposed to combat the challenge of financial toxicity in cancer care, an important strategy is the use of lower-priced drugs instead of expensive alternatives. However, the oncology community seems to either ignore or more readily reject cheaper drugs in cancer care compared to more expensive alternatives. In this commentary, we present three examples of lower-priced drugs rejected or ignored by the oncology community and contrast this with three expensive drugs where persistent optimism remained despite negative clinical trial results...
2018: Ecancermedicalscience
https://www.readbyqxmd.com/read/29448118/calcium-channel-blockers-as-drug-repurposing-candidates-for-gestational-diabetes-mining-large-scale-genomic-and-electronic-health-records-data-to-repurpose-medications
#2
Jeffery A Goldstein, Lisa A Bastarache, Joshua C Denny, Dan M Roden, Jill M Pulley, David M Aronoff
New therapeutic approaches are needed for gestational diabetes mellitus (GDM), but must show safety and efficacy in a historically understudied population. We studied associations between electronic medical record (EMR) phenotypes and genetic variants to uncover drugs currently considered safe in pregnancy that could treat or prevent GDM. We identified 129 systemically active drugs considered safe in pregnancy targeting the proteins produced from 196 genes. We tested for associations between GDM and/or type 2 diabetes (DM2) and 306 SNPs in 130 genes represented on the Illumina Infinium Human Exome Bead Chip (DM2 was included due to shared pathophysiological features with GDM)...
February 12, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29443902/repurposing-plant-virus-nanoparticles
#3
REVIEW
Kathleen L Hefferon
Plants have been explored for many years as inexpensive and versatile platforms for the generation of vaccines and other biopharmaceuticals. Plant viruses have also been engineered to either express subunit vaccines or act as epitope presentation systems. Both icosahedral and helical, filamentous-shaped plant viruses have been used for these purposes. More recently, plant viruses have been utilized as nanoparticles to transport drugs and active molecules into cancer cells. The following review describes the use of both icosahedral and helical plant viruses in a variety of new functions against cancer...
February 14, 2018: Vaccines
https://www.readbyqxmd.com/read/29435139/quantitative-high-throughput-phenotypic-screening-of-pediatric-cancer-cell-lines-identifies-multiple-opportunities-for-drug-repurposing
#4
Min Shen, Rosita Asawa, Ya-Qin Zhang, Elizabeth Cunningham, Hongmao Sun, Alexander Tropsha, William P Janzen, Eugene N Muratov, Stephen J Capuzzi, Sherif Farag, Ajit Jadhav, Julie Blatt, Anton Simeonov, Natalia J Martinez
Drug repurposing approaches have the potential advantage of facilitating rapid and cost-effective development of new therapies. Particularly, the repurposing of drugs with known safety profiles in children could bypass or streamline toxicity studies. We employed a phenotypic screening paradigm on a panel of well-characterized cell lines derived from pediatric solid tumors against a collection of ∼3,800 compounds spanning approved drugs and investigational agents. Specifically, we employed titration-based screening where compounds were tested at multiple concentrations for their effect on cell viability...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29432868/repurposing-niclosamide-for-intestinal-decolonization-of-vancomycin-resistant-enterococci
#5
Haroon Mohammad, Ahmed AbdelKhalek, Nader S Abutaleb, Mohamed N Seleem
Enterococci are commensal microorganisms present in the gastrointestinal (GI) tract of humans. Though normally innocuous to the host, strains of Enterococcus exhibiting resistance to vancomycin (VRE) have been associated with high rates of infection and mortality in immunocompromised patients. Decolonization of VRE represents a key strategy to curb infection in highly-susceptible patients. However, there is a dearth of decolonizing agents available clinically that are effective against VRE. The present study confirms that niclosamide, an anthelmintic drug, has potent antibacterial activity against clinical isolates of vancomycin-resistant E...
February 9, 2018: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/29429370/facile-development-characterization-and-optimization-of-new-metformin-loaded-nanocarrier-system-for-efficient-colon-cancer-adjunct-therapy
#6
Kholoud Arafa, Rehab N Shamma, Omaima N El-Gazayerly, Ibrahim M El-Sherbiny
PURPOSE: Metformin hydrochloride (MF) repurposing as adjuvant anticancer therapy for colorectal cancer (CRC) proved effective. Several studies attempted to develop MF-loaded nanoparticles (NPs), however the entrapment efficiency (EE%) was poor. Thus, the present study aimed at the facile development of a new series of chitosan (CS)-based semi-interpenetrating network (semi-IPN) NPs incorporating Pluronic ® nanomicelles as nanocarriers for enhanced entrapment and sustained release of MF for efficient treatment of CRC...
February 12, 2018: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29428725/antibiotic-ivermectin-selectively-induces-apoptosis-in-chronic-myeloid-leukemia-through-inducing-mitochondrial-dysfunction-and-oxidative-stress
#7
Jiaqiao Wang, Yanhua Xu, Huihui Wan, June Hu
Mitochondria has been a promising target in blood cancer given their unique dependencies on mitochondrial functions compared to normal hematopoietic cells. In line with this concept, we show that an anthelminthic drug ivermectin selectively kills chronic myeloid leukemia (CML) cells via inducing mitochondrial dysfunctions and oxidative stress. Ivermectin is significantly more effective in inducing caspase-dependent apoptosis in CML cell line K562 and primary CML CD34 than normal bone marrow (NBM) CD34 cells...
February 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29423610/repurposed-drugs-for-use-in-parkinson-s-disease
#8
Matthew D Smith, Kathryn J Peall
No abstract text is available yet for this article.
February 8, 2018: Journal of Neurology
https://www.readbyqxmd.com/read/29423540/do-statins-ace-inhibitors-or-sartans-improve-outcome-in-primary-glioblastoma
#9
Caroline Happold, Thierry Gorlia, L Burt Nabors, Sara C Erridge, David A Reardon, Christine Hicking, Martin Picard, Roger Stupp, Michael Weller
Glioblastomas are malignant brain tumors with poor prognosis. Lately, data from clinical studies assessing the role of co-medications in different cancer types suggested reduced mortality and potential anti-tumor activity for statins, angiotensin-I converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (sartans). Here, we analysed the association of co-treatment with statins, ACEI or sartans with outcome in a cohort of 810 patients enrolled in the phase III CENTRIC and phase II CORE trials on the role of the integrin antagonist, cilengitide, in newly diagnosed glioblastoma with or without O6-methylguanine DNA methyltransferase (MGMT) promoter methylation...
February 8, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29423274/a-diseasome-cluster-based-drug-repurposing-of-soluble-guanylate-cyclase-activators-from-smooth-muscle-relaxation-to-direct-neuroprotection
#10
Friederike Langhauser, Ana I Casas, Vu-Thao-Vi Dao, Emre Guney, Jörg Menche, Eva Geuss, Pamela W M Kleikers, Manuela G López, Albert-L Barabási, Christoph Kleinschnitz, Harald H H W Schmidt
Network medicine utilizes common genetic origins, markers and co-morbidities to uncover mechanistic links between diseases. These links can be summarized in the diseasome, a comprehensive network of disease-disease relationships and clusters. The diseasome has been influential during the past decade, although most of its links are not followed up experimentally. Here, we investigate a high prevalence unmet medical need cluster of disease phenotypes linked to cyclic GMP. Hitherto, the central cGMP-forming enzyme, soluble guanylate cyclase (sGC), has been targeted pharmacologically exclusively for smooth muscle modulation in cardiology and pulmonology...
2018: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/29423059/brain-and-brain-tumor-penetrating-disulfiram-nanoparticles-sequence-of-cytotoxic-events-and-efficacy-in-human-glioma-cell-lines-and-intracranial-xenografts
#11
Hanumantha Rao Madala, Surendra R Punganuru, Francis Ali-Osman, Ruiwen Zhang, Kalkunte S Srivenugopal
There is great interest in repurposing disulfiram (DSF), a rapidly metabolizing nontoxic drug, for brain cancers and other cancers. To overcome the instability and low therapeutic efficacy, we engineered passively-targeted DSF-nanoparticles (DSFNPs) using biodegradable monomethoxy (polyethylene glycol) d,l-lactic-co-glycolic acid (mPEG-PLGA) matrix. The physicochemical properties, cellular uptake and the blood brain-barrier permeability of DSFNPs were investigated. The DSFNPs were highly stable with a size of ∼70 nm with a >90% entrapment...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29414306/repurposing-psychiatric-drugs-as-anti-cancer-agents
#12
Jing Huang, Danwei Zhao, Zhixiong Liu, Fangkun Liu
Cancer is a major public health problem and one of the leading contributors to the global disease burden. The high cost of development of new drugs and the increasingly severe burden of cancer globally have led to increased interest in the search and development of novel, affordable anti-neoplastic medications. Antipsychotic drugs have a long history of clinical use and tolerable safety; they have been used as good targets for drug repurposing. Being used for various psychiatric diseases for decades, antipsychotic drugs are now reported to have potent anti-cancer properties against a wide variety of malignancies in addition to their antipsychotic effects...
February 1, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29407962/discovery-of-novel-mifepristone-derivatives-via-suppressing-klf5-expression-for-the-treatment-of-triple-negative-breast-cancer
#13
Yuqi Lin, Rong Liu, Ping Zhao, Jinxiang Ye, Zheng Zheng, Jingan Huang, Yingying Zhang, Yu Gao, Haiying Chen, Suling Liu, Jia Zhou, Ceshi Chen, Haijun Chen
Triple-negative breast cancer (TNBC) is one of the most malignant breast cancers currently with a lack of targeted therapeutic drugs. Accumulating evidence supports that KLF5 represents a novel therapeutic target for the treatment of basal TNBC. Our previous studies revealed that mifepristone is capable of suppressing TNBC cell proliferation and promoting cancer cell apoptosis by inhibiting KLF5 expression. Nevertheless, its anticancer efficacy is only modest with high dose. Moreover, its main metabolite N-desmethyl mifepristone with the removal of one methyl moiety results in a significant loss of antiproliferative activity, indicating an important pharmacophore domain around this methyl moiety...
February 2, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29405440/ebselen-inhibits-the-activity-of-acetylcholinesterase-globular-isoform-g4-in-vitro-and-attenuates-scopolamine-induced-amnesia-in-mice
#14
Franciele Martini, Ana Paula Pesarico, César Augusto Brüning, Gilson Zeni, Cristina Wayne Nogueira
There is a well-known relationship between the cholinergic system and learning, memory and other common cognitive processes. The process for researching and developing new drugs has lead researchers to repurpose older ones. This study investigated the effects of ebselen on the activity of acethylcholinesterase (AChE) isoforms in vitro and in an amnesia model induced by scopolamine in Swiss mice. In vitro, ebselen at concentrations equal or higher than 10 µM inhibited the activity of cortical and hippocampal G4/AChE, but not G1/AChE isoform...
February 5, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29401734/drug-repurposing-for-schistosomiasis-combinations-of-drugs-or-biomolecules
#15
REVIEW
Maria João Gouveia, Paul J Brindley, Fátima Gärtner, José M Correia da Costa, Nuno Vale
Schistosomiasis is a major neglected tropical disease. Control of schistosomiasis currently relies on a single drug, praziquantel, and despite its efficacy against the all schistosome species that parasitize humans, it displays some problematic drawbacks and alone is ineffective in counteracting adverse pathologies associated with infection. Moreover, due to the development of the potential emergence of PZQ-resistant strains, the search for additional or alternative antischistosomal drugs have become a public health priority...
February 5, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29399533/pathogenesis-of-thrombosis-cellular-and-pharmacogenetic-contributions
#16
REVIEW
Dileep D Monie, Emma P DeLoughery
Our understanding of thrombosis formation has evolved significantly ever since physician Rudolf Virchow proposed his "triad" theory in 1856. Modern science has elucidated the mechanisms of stasis, hypercoagulability, and endothelial dysfunction. Today, we have a firm understanding of the key molecular factors involved in the coagulation cascade and fibrinolytic system, as well as the underlying genetic influences. This knowledge of cellular and genetic contributors has been translated into diverse pharmaceutical interventions...
December 2017: Cardiovascular Diagnosis and Therapy
https://www.readbyqxmd.com/read/29386360/therapeutic-synergy-between-tigecycline-and-venetoclax-in-a-preclinical-model-of-myc-bcl2-double-hit-b-cell-lymphoma
#17
Micol Ravà, Aleco D'Andrea, Paola Nicoli, Ilaria Gritti, Giulio Donati, Mirko Doni, Marco Giorgio, Daniela Olivero, Bruno Amati
High-grade B cell lymphomas with concurrent activation of the MYC and BCL2 oncogenes, also known as double-hit lymphomas (DHL), show dismal prognosis with current therapies. MYC activation sensitizes cells to inhibition of mitochondrial translation by the antibiotic tigecycline, and treatment with this compound provides a therapeutic window in a mouse model of MYC-driven lymphoma. We now addressed the utility of this antibiotic for treatment of DHL. BCL2 activation in mouse Eμ-myc lymphomas antagonized tigecycline-induced cell death, which was specifically restored by combined treatment with the BCL2 inhibitor venetoclax...
January 31, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29382857/neuroprotective-drug-for-nerve-trauma-revealed-using-artificial-intelligence
#18
David Romeo-Guitart, Joaquim Forés, Mireia Herrando-Grabulosa, Raquel Valls, Tatiana Leiva-Rodríguez, Elena Galea, Francisco González-Pérez, Xavier Navarro, Valerie Petegnief, Assumpció Bosch, Mireia Coma, José Manuel Mas, Caty Casas
Here we used a systems biology approach and artificial intelligence to identify a neuroprotective agent for the treatment of peripheral nerve root avulsion. Based on accumulated knowledge of the neurodegenerative and neuroprotective processes that occur in motoneurons after root avulsion, we built up protein networks and converted them into mathematical models. Unbiased proteomic data from our preclinical models were used for machine learning algorithms and for restrictions to be imposed on mathematical solutions...
January 30, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29380703/structural-basis-of-antisickling-effects-of-selected-fda-approved-drugs-a-drug-repurposing-study
#19
Olujide O Olubiyi, Maryam O Olagunju, James O Oni, Abidemi O Olubiyi
Sickle cell disease is characterized by a point mutation involving substitution of glutamic acid at position 6 to valine. Encoded in this hydrophobic mutation is both an intrinsic capacity for the beta globin molecules to assemble into thermodynamically favoured polymeric states as well as a rational way of interrupting the aggregation. In this work, starting with a theoretical model that employs occlusive binding onto the beta globin aggregation surface and using a range of computational methods and an effective energy for screening, a number of FDA approved drugs with computed aggregation inhibitory activities were identified...
January 29, 2018: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/29367740/combined-chemical-genetics-and-data-driven-bioinformatics-approach-identifies-receptor-tyrosine-kinase-inhibitors-as-host-directed-antimicrobials
#20
Cornelis J Korbee, Matthias T Heemskerk, Dragi Kocev, Elisabeth van Strijen, Omid Rabiee, Kees L M C Franken, Louis Wilson, Nigel D L Savage, Sašo Džeroski, Mariëlle C Haks, Tom H M Ottenhoff
Antibiotic resistance poses rapidly increasing global problems in combatting multidrug-resistant (MDR) infectious diseases like MDR tuberculosis, prompting for novel approaches including host-directed therapies (HDT). Intracellular pathogens like Salmonellae and Mycobacterium tuberculosis (Mtb) exploit host pathways to survive. Only very few HDT compounds targeting host pathways are currently known. In a library of pharmacologically active compounds (LOPAC)-based drug-repurposing screen, we identify multiple compounds, which target receptor tyrosine kinases (RTKs) and inhibit intracellular Mtb and Salmonellae more potently than currently known HDT compounds...
January 24, 2018: Nature Communications
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