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Drug repurposing

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https://www.readbyqxmd.com/read/28927025/repurposing-itraconazole-for-the-treatment-of-cancer
#1
Rachel Pounds, Sarah Leonard, Christopher Dawson, Sean Kehoe
The repurposing of drugs is becoming increasingly attractive as it avoids the lengthy process and cost implications associated with bringing a novel drug to market. Itraconazole is a broad-spectrum anti-fungal agent. An emerging body of in vivo, in vitro and clinical evidence have confirmed that it also possesses antineoplastic activities and has a synergistic action when combined with other chemotherapeutic agents. It acts via several mechanisms to prevent tumour growth, including inhibition of the Hedgehog pathway, prevention of angiogenesis, decreased endothelial cell proliferation, cell cycle arrest and induction of auto-phagocytosis...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28925030/drug-repurposing-may-generate-novel-approaches-to-treating-depression
#2
REVIEW
Mohamed Elsaed Ebada
OBJECTIVES: The breakthrough advancements in scientific medical research have greatly improved our understanding of the pathogenesis of depression, encouraging drug discoverers to take a shorter path than ever through drug repurposing to generate new antidepressant medications. In addition to reduced noradrenergic and serotonergic neurotransmission in the brain, other coincidence features such as glutamate neurotoxicity, inflammation and/or cerebrovascular insufficiency are implicated in the pathogenesis of major depressive disorder and late-life depression...
September 18, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28924171/a-network-integration-approach-for-drug-target-interaction-prediction-and-computational-drug-repositioning-from-heterogeneous-information
#3
Yunan Luo, Xinbin Zhao, Jingtian Zhou, Jinglin Yang, Yanqing Zhang, Wenhua Kuang, Jian Peng, Ligong Chen, Jianyang Zeng
The emergence of large-scale genomic, chemical and pharmacological data provides new opportunities for drug discovery and repositioning. In this work, we develop a computational pipeline, called DTINet, to predict novel drug-target interactions from a constructed heterogeneous network, which integrates diverse drug-related information. DTINet focuses on learning a low-dimensional vector representation of features, which accurately explains the topological properties of individual nodes in the heterogeneous network, and then makes prediction based on these representations via a vector space projection scheme...
September 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28922811/a-programme-to-create-short-course-chemotherapy-for-pulmonary-mycobacterium-avium-disease-based-on-pharmacokinetics-pharmacodynamics-and-mathematical-forecasting
#4
Devyani Deshpande, Shashikant Srivastava, Tawanda Gumbo
Objectives: Pulmonary Mycobacterium avium complex (MAC) prevalence is on the rise worldwide. The average therapy duration is 1.5 years, which is associated with poor cure rates. Our objective was to develop a programme to design a combination therapy regimen for pulmonary MAC to be administered for 6 months or less with efficacy in > 90% of patients. Methods: We performed a literature search for the following MeSH headings 'Mycobacterium avium' AND 'pharmacokinetics/pharmacodynamics' in PubMed up to 2016...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28916199/erk-and-rock-functionally-interact-in-a-signaling-network-that-is-compensationally-upregulated-in-spinal-muscular-atrophy
#5
Niko Hensel, Svetlana Baskal, Lisa Marie Walter, Hella Brinkmann, Manuela Gernert, Peter Claus
Spinal Muscular Atrophy (SMA) is a motoneuron disease caused by low levels of functional survival of motoneuron protein (SMN). Molecular disease mechanisms downstream of functional SMN loss are still largely unknown. Previous studies suggested an involvement of Rho kinase (ROCK) as well as the extracellular signal-regulated kinases (ERK) pathways in the pathomechanism. Both pathways are bi-directionally linked and inhibit each other. Thus, we hypothesize that both pathways regulate SMA pathophysiology in vivo in a combined manner rather than acting separately...
September 12, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28912539/diphenyleneiodonium-chloride-dpic-displays-broad-spectrum-bactericidal-activity
#6
Manitosh Pandey, Alok Kumar Singh, Ritesh Thakare, Sakshi Talwar, Pratiksha Karaulia, Arunava Dasgupta, Sidharth Chopra, Amit Kumar Pandey
Indiscriminate use of antibiotics globally has lead to an increase in emergence of drug-resistant pathogens under both nosocomial, as well as more worryingly, in community setting as well. Further, a decrease in the corporate interest and financial commitment has exerted increasing pressure on a rapidly dwindling antimicrobial drug discovery and developmental program. In this context, we have screened the Library of Pharmacologically Active Compounds (LOPAC, Sigma) against Staphylococcus aureus and Mycobacterium tuberculosis to identify potent novel antimicrobial molecules amongst non-antibiotic molecules...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912011/cell-line-dependent-antiviral-activity-of-sofosbuvir-against-zika-virus
#7
Noreen Mumtaz, Leah C Jimmerson, Lane R Bushman, Jennifer J Kiser, Georgina Aron, Chantal B E M Reusken, Marion P G Koopmans, Jeroen J A van Kampen
The recent epidemic of Zika virus (ZIKV) in the Americas and its association with fetal and neurological complications has shown the need to develop a treatment. Repurposing of drugs that are already FDA approved or in clinical development may shorten drug development timelines in case of emerging viral diseases like ZIKV. Initial studies have shown conflicting results when testing sofosbuvir developed for treatment of infections with another Flaviviridae virus, hepatitis C virus. We hypothesized that the conflicting results could be explained by differences in intracellular processing of the compound...
September 11, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28910823/camptothecin-suppresses-nrf2-are-activity-and-sensitises-hepatocellular-carcinoma-cells-to-anticancer-drugs
#8
Feng Chen, Huihui Wang, Jiayu Zhu, Rui Zhao, Peng Xue, Qiang Zhang, M Bud Nelson, Weidong Qu, Bo Feng, Jingbo Pi
BACKGROUND: Resistance to chemotherapy is a major obstacle in the treatment of human hepatocellular carcinoma (HCC). Despite playing an important role in chemoprevention, nuclear factor erythroid 2-related factor 2 (NRF2) also contributes to chemo- and radio-resistance. The current study focusses on camptothecin as a novel NRF2 inhibitor to sensitise HCC to chemotherapy. METHODS: The expression and transcriptional activity of NRF2 in human HCC biopsies and camptothecin-treated culture cells were determined using immunostaining, western blot, reverse-transcription quantitative real-time PCR (RT-qPCR) and luciferase reporter assay...
September 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28900159/computational-cell-cycle-profiling-of-cancer-cells-for-prioritizing-fda-approved-drugs-with-repurposing-potential
#9
Yu-Chen Lo, Silvia Senese, Bryan France, Ankur A Gholkar, Robert Damoiseaux, Jorge Z Torres
Discovery of first-in-class medicines for treating cancer is limited by concerns with their toxicity and safety profiles, while repurposing known drugs for new anticancer indications has become a viable alternative. Here, we have developed a new approach that utilizes cell cycle arresting patterns as unique molecular signatures for prioritizing FDA-approved drugs with repurposing potential. As proof-of-principle, we conducted large-scale cell cycle profiling of 884 FDA-approved drugs. Using cell cycle indexes that measure changes in cell cycle profile patterns upon chemical perturbation, we identified 36 compounds that inhibited cancer cell viability including 6 compounds that were previously undescribed...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28895472/aldo-keto-reductase-akr-1c3-inhibitors-a-patent-review
#10
Trevor M Penning
AKR1C3 is a drug target in hormonal and hormonal independent malignancies and acts as a major peripheral 17β -hydroxysteroid dehydrogenase to yield the potent androgens testosterone and dihydrotestosterone, and as a prostaglandin (PG) F synthase to produce proliferative ligands for the PG FP receptor. AKR1C3 inhibitors may have distinct advantages over existing therapeutics for the treatment of castration resistant prostate cancer, breast cancer and acute myeloid leukemia. Area Covered: This article reviews the patent literature on AKR1C3 inhibitors using SciFinder which identified inhibitors in the following chemical classes: N-phenylsulfonyl-indoles, N-(benzimidazoylylcarbonyl)- N-(indoylylcarbonyl)- and N-(pyridinepyrrolyl)- piperidines, N-benzimidazoles and N-benzindoles, repurposed nonsteroidal antiinflammatory drugs (indole acetic acids, N-phenylanthranilates and aryl propionic acids), isoquinolines, and nitrogen and sulfur substituted estrenes...
September 12, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28880396/drug-repurposing-to-treat-asthma-and-allergic-disorders-progress-and-prospects
#11
REVIEW
Robert L Kruse, Kristine Vanijcharoenkarn
Allergy and atopic asthma have continued to become more prevalent in modern society despite the advent of new treatments, representing a major global health problem. Common medications such as antihistamines and steroids may have undesirable long-term side effects and lack efficacy in some resistant patients. Biologic medications are increasingly given to treat resistant patients, but they can represent high costs, complex dosing and management, and are not widely available around the world. The field needs new, cheap and convenient treatment options in order to bring better symptom relief to patients...
September 7, 2017: Allergy
https://www.readbyqxmd.com/read/28877446/role-of-ion-channels-in-natural-killer-cell-function-towards-cancer
#12
John Redmond, Debbie O'Rilley, Paul Buchanan
Progression of cancer to advanced states is associated with treatment resistance and metastatic spread -- features that are linked to poor prognosis and patient mortality. Investigations into potential new treatments to reduce cancer spread are ongoing, with immunotherapy generating much interest. Natural killer (NK) cells are part of the body's innate immune system and are known for their ability to target and lyse cancer cells. Ion channels have previously been linked to the growth and development of tumors, but recent research suggests that these channels may also serve to alter immune cell functioning...
June 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28874314/drug-discovery-for-the-treatment-of-substance-use-disorders-novel-targets-repurposing-and-the-need-for-new-paradigms
#13
REVIEW
Cristiano Chiamulera, Laura Padovani, Mauro Corsi
Drug addiction treatment medications available nowadays are limited in both efficacy and number. The increased understanding of drug addiction circuitries leads the scientific community to look for better molecules and targets for detoxification and relapse prevention. This review focus on known targets (e.g., metabotropic glutamate receptor 5 and GABAB receptor) and on novel potential treatment acting on oxytocin system, which interacts with diverse neurotransmitters, has proved successful in both preclinical and clinical studies on ethanol, cocaine and methamphetamine...
September 2, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28873428/evaluation-of-robenidine-analog-ncl195-as-a-novel-broad-spectrum-antibacterial-agent
#14
Abiodun D Ogunniyi, Manouchehr Khazandi, Andrew J Stevens, Sarah K Sims, Stephen W Page, Sanjay Garg, Henrietta Venter, Andrew Powell, Karen White, Kiro R Petrovski, Geraldine Laven-Law, Eliane G Tótoli, Hérida R Salgado, Hongfei Pi, Geoffrey W Coombs, Dean L Shinabarger, John D Turnidge, James C Paton, Adam McCluskey, Darren J Trott
The spread of multidrug resistance among bacterial pathogens poses a serious threat to public health worldwide. Recent approaches towards combating antimicrobial resistance include repurposing old compounds with known safety and development pathways as new antibacterial classes with novel mechanisms of action. Here we show that an analog of the anticoccidial drug robenidine (4,6-bis(2-((E)-4-methylbenzylidene)hydrazinyl)pyrimidin-2-amine; NCL195) displays potent bactericidal activity against Streptococcus pneumoniae and Staphylococcus aureus by disrupting the cell membrane potential...
2017: PloS One
https://www.readbyqxmd.com/read/28870526/drug-repurposing-strategy-against-trypanosoma-cruzi-infection-in-vitro-and-in-vivo-assessment-of-the-activity-of-metronidazole-in-mono-and-combined-therapy
#15
M R Simões-Silva, J S De Araújo, G M Oliveira, K C Demarque, R B Peres, I D'Almeida-Melo, D G J Batista, C F Da Silva, C Cardoso-Santos, P B Da Silva, M M Batista, M T Bahia, M N C Soeiro
Metronidazole (Mtz) is a commercial broad-spectrum nitroimidazolic derivative with relevant antimicrobial activity and relative safety profile. Therefore, it is fair to consider Mtz a candidate for drug repurposing for other neglected conditions such as Chagas disease (CD), a parasitic pathology caused by Trypanosoma cruzi. CD is treated only with benznidazole (Bz) and nifurtimox, both introduced in clinics decades ago despite important limitations, including low efficacy on the later disease stage (chronic form) and severe side effects...
September 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28864377/antiviral-drug-ribavirin-targets-thyroid-cancer-cells-by-inhibiting-the-eif4e-%C3%AE-catenin-axis
#16
Xiawei Shen, Yali Zhu, Zuixuan Xiao, Xuemei Dai, Dan Liu, Lin Li, Baolai Xiao
BACKGROUND: Although eukaryotic translation initiation factor 4E (eIF4E) is important in cancer development and progression, its role in thyroid cancer is not well understood. Ribavirin, an anti-viral drug, has been identified as an eIF4E inhibitor. Herein, we investigated the effects of ribavirin on thyroid cancer and its molecular mechanisms of action. MATERIALS AND METHODS: The effects of ribavirin on thyroid cancer was investigated using in vitro cellular assays and in vivo xenograft mouse model...
August 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28864360/current-treatment-options-and-the-role-of-peptides-as-potential-therapeutic-components-for-middle-east-respiratory-syndrome-mers-a-review
#17
REVIEW
Sabeena Mustafa, Hanan Balkhy, Musa Nur Gabere
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a highly pathogenic respiratory virus with mechanisms that may be driven by innate immune responses. Despite the effort of scientific studies related to this virus, Middle East Respiratory Syndrome (MERS) is still a public health concern. MERS-CoV infection has a high mortality rate, and to date, no therapeutic or vaccine has been discovered, that is effective in treating or preventing the disease. In this review, we summarize our understanding of the molecular and biological events of compounds acting as MERS-CoV inhibitors, the outcomes of existing therapeutic options and the various drugs undergoing clinical trials...
August 29, 2017: Journal of Infection and Public Health
https://www.readbyqxmd.com/read/28864067/a-novel-chemoradiation-targeting-stem-and-nonstem-pancreatic-cancer-cells-by-repurposing-disulfiram
#18
Juan Cong, Yangyang Wang, Xiao Zhang, Nan Zhang, Ling Liu, Klara Soukup, Theodoros Michelakos, Theodore Hong, Albert DeLeo, Lei Cai, Francesco Sabbatino, Soldano Ferrone, Hang Lee, Vera Levina, Bryan Fuchs, Kenneth Tanabe, Keith Lillemoe, Cristina Ferrone, Xinhui Wang
Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate of 6% and is projected to be the second leading cause of cancer death by 2030, underscoring the urgency to develop new strategies to improve current therapeutic modalities for PDAC. Targeting pancreatic cancer stem cells (PCSCs), which are resistant to radiation and chemotherapy, is a promising strategy. A novel approach which can be readily clinically translated is to repurpose disulfiram (DSF), a drug for treating alcoholism, to target PCSCs...
August 30, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28860008/a-signalome-screening-approach-in-the-autoinflammatory-disease-tnf-receptor-associated-periodic-syndrome-traps-highlights-the-anti-inflammatory-properties-of-drugs-for-repurposing
#19
Ian Todd, Ola H Negm, Jenna Reps, Paul Radford, Grazziela Figueredo, Elizabeth M McDermott, Elizabeth Drewe, Richard J Powell, Susan Bainbridge, Mohamed Hamed, Sharon Crouch, Jon Garibaldi, Steve St-Gallay, Lucy C Fairclough, Patrick J Tighe
TNF Receptor Associated Periodic Syndrome (TRAPS) is an autoinflammatory disease caused by mutations in TNF Receptor 1 (TNFR1). Current therapies for TRAPS are limited and do not target the pro-inflammatory signalling pathways that are central to the disease mechanism. Our aim was to identify drugs for repurposing as anti-inflammatories based on their ability to down-regulate molecules associated with inflammatory signalling pathways that are activated in TRAPS. This was achieved using rigorously optimised, high through-put cell culture and reverse phase protein microarray systems to screen compounds for their effects on the TRAPS-associated inflammatory signalome...
August 28, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28855357/chemogenomic-landscape-of-runx1-mutated-aml-reveals-importance-of-runx1-allele-dosage-in-genetics-and-glucocorticoid-sensitivity
#20
Laura Simon, Vincent-Philippe Lavallée, Marie-Eve Bordeleau, Jana Krosl, Irene Baccelli, Geneviève Boucher, Bernhard Lehnertz, Jalila Chagraoui, Tara MacRae, Réjean Ruel, Yves A Chantigny, Sébastien Lemieux, Anne Marinier, Josée Hébert, Guy Sauvageau
PURPOSE: RUNX1-mutated (RUNX1mut) Acute Myeloid Leukemia (AML) is associated with adverse outcome, highlighting the urgent need for a better genetic characterization of this AML subgroup and for the design of efficient therapeutic strategies for this disease. Towards this goal, we further dissected the mutational spectrum and gene expression profile of RUNX1mut AML and correlated these results to drug sensitivity to identify novel compounds targeting this AML subgroup. EXPERIMENTAL DESIGN: RNA-sequencing of 47 RUNX1mut primary AML specimens was performed and sequencing results were compared to those of RUNX1 wild-type samples...
August 30, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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