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Repurposing drugs

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https://www.readbyqxmd.com/read/28715462/cell-specificity-dictates-similarities-in-gene-expression-in-multiple-sclerosis-parkinson-s-disease-and-alzheimer-s-disease
#1
Yuichiro Itoh, Rhonda R Voskuhl
Drug repurposing is an efficient approach in new treatment development since it leverages previous work from one disease to another. While multiple sclerosis (MS), Parkinson's disease (PD), and Alzheimer's disease (AD) are all neurodegenerative diseases of the central nervous system (CNS) and differ in many clinical and pathological aspects, it is possible that they may share some mechanistic features. We hypothesized that focusing on gene expression in a CNS cell type specific manner might uncover similarities between diseases that could be missed using whole tissue gene expression analyses...
2017: PloS One
https://www.readbyqxmd.com/read/28712971/drug-repurposing-in-cancer
#2
REVIEW
Linda Sleire, Hilde Elisabeth Førde, Inger Anne Netland, Lina Leiss, Per Øyvind Enger
Cancer is a major health issue worldwide, and the global burden of cancer is expected to increase in the coming years. Whereas the limited success with current therapies has driven huge investments into drug development, the average number of FDA approvals per year has declined since the 1990s. This unmet need for more effective anti-cancer drugs has sparked a growing interest for drug repurposing, i.e. using drugs already approved for other indications to treat cancer. As such, data both from pre-clinical experiments, clinical trials and observational studies have demonstrated anti-tumor efficacy for compounds within a wide range of drug classes other than cancer...
July 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28711146/drug-repositioning-strategies-for-the-identification-of-novel-therapies-for-rheumatic-autoimmune-inflammatory-diseases
#3
REVIEW
Amrie C Grammer, Peter E Lipsky
Rheumatic Autoimmune Inflammatory Diseases such as Sjögren's and lupus lack modern treatments. Less than 5% of drugs approved by the FDA from 2014 to mid-2016 had a RAID indication. Many RAID standard-of-care drugs were repurposed based on serendipitous observations, similarity-of-disease categorization, and/or off-target effects. Recently, drug repurposing has become more intentional, relying on an evolving awareness of molecular underpinnings, as well as a better understanding of drug-target interactions by computational modeling...
August 2017: Rheumatic Diseases Clinics of North America
https://www.readbyqxmd.com/read/28710230/the-tissue-reconstructing-ability-of-colon-cscs-is-enhanced-by-fk506-and-suppressed-by-gsk3-inhibition
#4
Ryo Ishida, Michiyo Koyanagi-Aoi, Nobu Oshima, Yoshihiro Kakeji, Takashi Aoi
Cancer stem cells (CSCs) are capable of reconstructing cancer tissues, are involved in both recurrence and metastasis, and contribute to therapeutic resistance. Therefore, elucidating the molecular mechanism in CSCs is important to successfully treat unresectable cancers. Previously we observed that colon cancer stem-like cells can be induced from human colon cancer cell lines by retrovirally introducing OCT3/4, SOX2 and KLF4, and we have designated such cells as induced cancer stem cells (iCSCs). In the current study, we used iCSCs to evaluate the molecular mechanism of colon CSCs and developed new methods to control them...
July 14, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28708269/heme-oxygenase-database-hemeoxdb-and-qsar-analysis-of-isoform-1-inhibitors
#5
Emanuele Amata, Agostino Marrazzo, Maria Dichiara, Maria N Modica, Loredana Salerno, Orazio Prezzavento, Giovanni Nastasi, Antonio Rescifina, Giuseppe Romeo, Valeria Pittalà
Due to the increasing interest in the field of heme oxygenases (HOs), we have built a ligand database named HemeOxDB that includes the entire set of known HO-1 and HO-2 inhibitors, resulting in more than 400 compounds. The HemeOxDB is available online at http://www.researchdsf.unict.it/hemeoxdb/, and having a robust search engine allows the end-users to build complex queries, sort tabulated results, generate color coded 2D (two dimension) and 3D (three dimension) graphs, and is will grow to be a tool for the design of potent and selective HO-1 or HO-2 inhibitors...
July 14, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28694231/repurposing-ivacaftor-for-treatment-of-staphylococcus-aureus-infections
#6
Ritesh Thakare, Alok Kumar Singh, Swetarka Das, N Vasudevan, Gorakhnath R Jachak, D Srinivas Reddy, Arunava Dasgupta, Sidharth Chopra
Drug repurposing of non-antimicrobials is a novel method to augment a seriously depleted drug pipeline for targeting drug-resistant pathogens. This article highlights the potent antimicrobial activity of Ivacaftor against Staphylococcus aureus, including vancomycin- and other multidrug-resistant strains. The potent activity of Ivacaftor in vivo is also demonstrated in a murine neutropenic thigh infection model. Taken together, these results support the potential of Ivacaftor as an antimicrobial agent for the treatment of staphylococcal infections...
July 7, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28692063/inflammation-dependent-cerebrospinal-fluid-hypersecretion-by-the-choroid-plexus-epithelium-in-posthemorrhagic-hydrocephalus
#7
Jason K Karimy, Jinwei Zhang, David B Kurland, Brianna Carusillo Theriault, Daniel Duran, Jesse A Stokum, Charuta Gavankar Furey, Xu Zhou, M Shahid Mansuri, Julio Montejo, Alberto Vera, Michael L DiLuna, Eric Delpire, Seth L Alper, Murat Gunel, Volodymyr Gerzanich, Ruslan Medzhitov, J Marc Simard, Kristopher T Kahle
The choroid plexus epithelium (CPE) secretes higher volumes of fluid (cerebrospinal fluid, CSF) than any other epithelium and simultaneously functions as the blood-CSF barrier to gate immune cell entry into the central nervous system. Posthemorrhagic hydrocephalus (PHH), an expansion of the cerebral ventricles due to CSF accumulation following intraventricular hemorrhage (IVH), is a common disease usually treated by suboptimal CSF shunting techniques. PHH is classically attributed to primary impairments in CSF reabsorption, but little experimental evidence supports this concept...
July 10, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28689769/osteoporosis-treatment-recent-developments-and-ongoing-challenges
#8
REVIEW
Sundeep Khosla, Lorenz C Hofbauer
Osteoporosis is an enormous and growing public health problem. Once considered an inevitable consequence of ageing, it is now eminently preventable and treatable. Ironically, despite tremendous therapeutic advances, there is an increasing treatment gap for patients at high fracture risk. In this Series paper, we trace the evolution of drug therapy for osteoporosis, which began in the 1940s with the demonstration by Fuller Albright that treatment with oestrogen could reverse the negative calcium balance that developed in women after menopause or oophorectomy...
July 6, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28685814/drug-repurposing-screens-and-synergistic-drug-combinations-for-infectious-diseases
#9
REVIEW
Wei Zheng, Wei Sun, Anton Simeonov
Infectious diseases account for nearly one fifth of the worldwide death toll every year. Continuous increase of drug-resistant pathogens is a big challenge for treatment of infectious diseases. In addition, emerging outbreaks of infections and new pathogens are potential threats to public health. Lack of effective treatments for drug-resistant bacteria and recent outbreaks of Ebola and Zika viral infections have become a global public health concern. The number of newly approved antibiotics has decreased significantly in the last two decades compared to previous decades...
July 7, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28684712/decaf-discrimination-comparison-alignment-tool-for-2d-pharmacophores
#10
Marta M Stepniewska-Dziubinska, Piotr Zielenkiewicz, Pawel Siedlecki
Comparison of small molecules is a common component of many cheminformatics workflows, including the design of new compounds and libraries as well as side-effect predictions and drug repurposing. Currently, large-scale comparison methods rely mostly on simple fingerprint representation of molecules, which take into account the structural similarities of compounds. Methods that utilize 3D information depend on multiple conformer generation steps, which are computationally expensive and can greatly influence their results...
July 6, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28683214/new-therapeutic-targets-for-osteoarthritis-pain
#11
David A Walsh, Joanne Stocks
Osteoarthritis (OA), the most common form of arthritis, causes pain and disability, as well as emotional distress. While total joint replacement is one of the most effective treatments available for improving the quality of life in people with severe OA, it is not suitable for all patients and all joints. Current pharmacological analgesics have limited efficacy, and their use is often restricted by adverse events. Medications that might reduce pain by slowing or preventing structural disease remain elusive...
July 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28682452/mitochondrial-dysfunction-and-potential-anticancer-therapy
#12
REVIEW
Matilde E Lleonart, Robert Grodzicki, Dmitri M Graifer, Alex Lyakhovich
Mitochondrial dysfunction (MDF) has been identified as an important factor in various diseases ranging from neurological disorders, to diseases of the cardiovascular system and metabolic syndromes. MDF was also found in cancer as well as in cancer predisposition syndromes with defective DNA damage response (DDR) machinery. Moreover, a recent highlight arises from the detection of MDF in eukaryotic cells upon treatment with antibiotics. In this review, we focus on recent studies of MDF in pathological conditions with a particular emphasis on the effects of various classes of antibiotics on mitochondria...
July 6, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28676484/a-therapy-for-fxs
#13
Leslie K Ferrarelli
The antidiabetic drug metformin might be repurposed to treat patients with fragile X syndrome.
July 4, 2017: Science Signaling
https://www.readbyqxmd.com/read/28674055/screening-the-mmv-pathogen-box-across-multiple-pathogens-reclassifies-starting-points-for-open-source-drug-discovery
#14
Sandra Duffy, Melissa L Sykes, Amy J Jones, Todd B Shelper, Moana Simpson, Rebecca Lang, Sally-Ann Poulsen, Brad E Sleebs, Vicky M Avery
Open access drug discovery provides a substantial resource for diseases primarily affecting the poor and disadvantaged. The open access Pathogen Box is comprised of a collection of compounds with demonstrated biological activity against specific pathogenic organisms. The supply of this resource by the Medicines for Malaria Venture has the potential to provide new chemical starting points for a number of tropical and neglected diseases, through repurposing of these compounds for use in drug discovery campaigns for these additional pathogens...
July 3, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28674046/repurposing-thiram-and-disulfiram-as-antibacterial-agents-for-multi-drug-resistant-staphylococcus-aureus-infections
#15
Timothy E Long
Thiram and disulfiram were evaluated as antibacterial agents against multidrug resistant Staphylococcus aureus Against a 30 member panel comprised of vancomycin-susceptible (VSSA), vancomycin-intermediate (VISA) and vancomycin-resistant (VRSA) strains, the MIC90 values of the respective test agents were 4 and 16 μg/mL. Additional analyses revealed that thiram and disulfiram are rapid-acting bacteriostatic agents with narrow, Gram-positive bacteria spectrum activity. Synergy studies further determined that disulfiram increases the vancomycin susceptibility of three clinical VRSA strains in vitro, thus establishing a potential use in combination therapy...
July 3, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28663722/bacoside-a-induces-tumor-cell-death-in-human-glioblastoma-cell-lines-through-catastrophic-macropinocytosis
#16
Sebastian John, K C Sivakumar, Rashmi Mishra
Glioblastoma multiforme (GBM) is a highly aggressive type of brain tumor with an extremely poor prognosis. Recent evidences have shown that the "biomechanical imbalances" induced in GBM patient-derived glioblastoma cells (GC) and in vivo via the administration of synthetic small molecules, may effectively inhibit disease progression and prolong survival of GBM animal models. This novel concept associated with de novo anti-GBM drug development has however suffered obstacles in adequate clinical utility due to the appearance of unrelated toxicity in the prolonged therapeutic windows...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28662711/repurposing-propranolol-as-a-drug-for-the-treatment-of-retinal-haemangioblastomas-in-von-hippel-lindau-disease
#17
Virginia Albiñana, Rosa María Jiménez Escribano, Isabel Soler, Luis Rodríguez Padial, Lucia Recio-Poveda, Karina Villar Gómez de Las Heras, Luisa María Botella
BACKGROUND: Von Hippel-Lindau (VHL) disease is a rare oncological disease with an incidence of 1:36,000, and is characterized by the growth of different types of tumours. Haemangioblastomas in the central nervous system (CNS) and retina, renal carcinoma and pheochromocytomas are the most common tumours. The absence of treatment for VHL leads to the need of repeated surgeries as the only option for these patients. Targeting VHL-derived tumours with drugs with reduced side effects is urgent to avoid repeated CNS surgeries...
June 29, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28655823/can-an-fda-approved-alzheimer-s-drug-be-repurposed-for-alleviating-neuronal-symptoms-of-zika-virus
#18
Devika Sirohi, Richard J Kuhn
Zika virus caught the world by surprise by its rapid spread and frightening disease outcomes. This major epidemic motivated many scientists to focus their attention on controlling this emerging pathogen. As many as 45 vaccine candidates are being developed, but progress in the antiviral arena has been slower. In a recent article (mBio 8:e00350-17, 2017, https://doi.org/10.1128/mBio.00350-17), Costa and colleagues showed that an FDA-approved drug used to treat Alzheimer's disease may moderate Zika virus-induced neuronal damage...
June 27, 2017: MBio
https://www.readbyqxmd.com/read/28652232/characterization-of-a-francisella-tularensis-caenorhabditis-elegans-pathosystem-for-the-evaluation-of-therapeutic-compounds
#19
Elamparithi Jayamani, Nagendran Tharmalingam, Rajmohan Rajamuthiah, Jeffrey J Coleman, Wooseong Kim, Ikechukwu Okoli, Ana M Hernandez, Kiho Lee, Gerard J Nau, Frederick M Ausubel, Eleftherios Mylonakis
Francisella tularensis is a highly infectious Gram-negative intracellular pathogen that causes tularemia. Because of its potential as a bioterrorism agent, there is a need for new therapeutic agents. We therefore developed a whole animal Caenorhabditis elegans-F. tularensis pathosystem for high throughput screening to identify and characterize potential therapeutic compounds. We found that the C. elegans p38 MAP kinase cascade is involved in the immune response to F. tularensis and we developed a robust F. tularensis-mediated C...
June 26, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28644007/cyclotides-as-tools-in-chemical-biology
#20
Simon J de Veer, Joachim Weidmann, David J Craik
Among the various molecules that plants produce for defense against pests and pathogens, cyclotides stand out as exceptionally stable and structurally unique. These ribosomally synthesized peptides are around 30 amino acids in size, and are stabilized by a head-to-tail cyclic peptide backbone and three disulfide bonds that form a cystine knot. They occur in certain plants of the Rubiaceae, Violaceae, Cucurbitaceae, Fabaceae, and Solanaceae families, with an individual plant producing up to hundreds of different cyclotides...
June 23, 2017: Accounts of Chemical Research
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