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https://www.readbyqxmd.com/read/28635653/virtual-screening-against-phosphoglycerate-kinase-1-in-quest-of-novel-apoptosis-inhibitors
#1
Jie Xia, Bo Feng, Qianhang Shao, Yuhe Yuan, Xiang Simon Wang, Naihong Chen, Song Wu
Inhibition of apoptosis is a potential therapy to treat human diseases such as neurodegenerative disorders (e.g., Parkinson's disease), stroke, and sepsis. Due to the lack of druggable targets, it remains a major challenge to discover apoptosis inhibitors. The recent repositioning of a marketed drug (i.e., terazosin) as an anti-apoptotic agent uncovered a novel target (i.e., human phosphoglycerate kinase 1 (hPgk1)). In this study, we developed a virtual screening (VS) pipeline based on the X-ray structure of Pgk1/terazosin complex and applied it to a screening campaign for potential anti-apoptotic agents...
June 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28634268/30-years-of-the-mineralocorticoid-receptor-mineralocorticoid-receptor-antagonists-60-years-of-research-and-development
#2
REVIEW
Peter Kolkhof, Lars Bärfacker
The cDNA of the mineralocorticoid receptor (MR) was cloned 30 years ago, in 1987. At that time, spirolactone, the first generation of synthetic steroid-based MR antagonists (MRAs), which was identified in preclinical in vivo models, had already been in clinical use for 30 years. Subsequent decades of research and development by Searle & Co., Ciba-Geigy, Roussel Uclaf and Schering AG toward identifying a second generation of much more specific steroidal MRAs were all based on the initial 17-spirolactone construct...
July 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28633899/discovery-of-bms-961955-an-allosteric-inhibitor-of-the-hepatitis-c-virus-ns5b-polymerase
#3
Barbara Zhizhen Zheng, Stanley V D'Andrea, Umesh Hanumegowda, Jay O Knipe, Kathy Mosure, Xiaoliang Zhuo, Julie A Lemm, Mengping Liu, Karen L Rigat, Ying-Kai Wang, Hua Fang, Chris Poronsky, Jingfang Cutrone, Dauh-Rurng Wu, Pirama Nayagam Arunachalam, T J Balapragalathan, Arunachalam Arumugam, Arvind Mathur, Nicholas A Meanwell, Min Gao, Susan B Roberts, John F Kadow
The synthesis, structure-activity relationship (SAR) data, and further optimization of the metabolic stability and pharmacokinetic (PK) properties for a previously disclosed class of cyclopropyl-fused indolobenzazepine HCV NS5B polymerase inhibitors are described. These efforts led to the discovery of BMS-961955 as a viable contingency backup to beclabuvir which was recently approved in Japan for the treatment of HCV as part of a three drug, single pill combination marketed as Ximency(TM).
June 11, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28632830/-declaration-of-the-chilean-academy-of-medicine-of-law-20-850-on-clinical-trials-of-pharmaceutical-products-and-medical-devices-and-of-the-bylaw-that-will-regulate-its-application
#4
Gloría López, Gloría Valdés, Emilio Roessler, Vicente Valdivieso
In Chile, high cost treatments required by selected medical conditions are financed by the State, according to Law 20.850. A bylaw under discussion by the Senate regulates clinical trials, posing complex issues that will endanger local interest in front-line research: 1) The exclusive and mandatory control bestowed to the Institute of Public Health during all stages of the trials and also the surveillance of institutions performing clinical trials, overriding their Clinical Research Review Boards; 2) The 10 year period during which any adverse event is assumed to have been caused by the medication or devise evaluated by the trial, unless the contrary is proven in a judicial process; 3) Individuals submitted to the trials are entitled to free post trial access to the treatment received during the study, financed by the trial supporting entities and as long as the drug or devise is considered to be useful...
April 2017: Revista Chilena de Infectología: órgano Oficial de la Sociedad Chilena de Infectología
https://www.readbyqxmd.com/read/28632332/microscale-disruption-of-microorganisms-for-parallelized-process-development
#5
REVIEW
Cornelia Walther, Astrid Dürauer
Escherichia coli, Saccharomyces cerevisiae, and Pichia pastoris are the standard platforms for biopharmaceutical production with 40% of all between 2010 to 2014 approved protein drugs produced in those microbial hosts. Typically, products overexpressed E. coli and S. cerevisiae remain in the cytosol or are secreted into the periplasm. Consequently, efficient cell disruption is essential for high product recovery during microbial production. Process development platforms at microscale are essential to shorten time to market...
June 20, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28630942/antimalarial-drugs-and-the-prevalence-of-mental-and-neurological-manifestations-a-systematic-review-and-meta-analysis
#6
Mary A Bitta, Symon M Kariuki, Clifford Mwita, Samson Gwer, Leah Mwai, Charles R J C Newton
Background: Antimalarial drugs affect the central nervous system, but it is difficult to differentiate the effect of these drugs from that of the malaria illness. We conducted a systematic review to determine the association between anti-malarial drugs and mental and neurological impairment in humans.  Methods: We systematically searched online databases, including Medline/PubMed, PsychoInfo, and Embase, for articles published up to 14th July 2016. Pooled prevalence, heterogeneity and factors associated with prevalence of mental and neurological manifestations were determined using meta-analytic techniques...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28630559/drug-policy-and-indigenous-peoples
#7
Julian Burger, Mary Kapron
This paper identifies the principal concerns of indigenous peoples with regard to current international treaties on certain psychoactive substances and policies to control and eradicate their production, trafficking, and sale. Indigenous peoples have a specific interest in the issue since their traditional lands have become integrated over time into the large-scale production of coca, opium poppy, and cannabis crops, in response to high demand from the American and European markets, among others. As a consequence, indigenous peoples are persecuted because of their traditional use of these and other plant-based narcotics and hallucinogens...
June 2017: Health and Human Rights
https://www.readbyqxmd.com/read/28629531/survey-of-traditional-dai-medicine-reveals-species-confusion-and-potential-safety-concerns-a-case-study-on-radix-clerodendri-japonicum
#8
Bao-Zhong Duan, Hai-Lan Fang, Xi-Wen Li, Lin-Fang Huang, Wang Ping, Shi-Lin Chen
The adulteration of herbal products is a threat to consumer safety. In the present study, we surveyed the species composition of commercial Radix Clerodendri Japonicum products using DNA barcoding as a supervisory method. A reference database for plant-material DNA-barcode was successfully constructed with 48 voucher samples from 12 Clerodendrum species. The database was used to identify 27 Radix Clerodendri Japonicum decoction piece samples purchased from drug stores and hospitals. The DNA sequencing results revealed that only 1 decoction piece (3...
June 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28628897/diverted-medications-and-new-psychoactive-substances-a-chemical-network-analysis-of-discarded-injecting-paraphernalia-in-hungary
#9
Valéria Anna Gyarmathy, Anna Péterfi, Tamás Figeczki, József Kiss, Katalin Medgyesi-Frank, János Posta, József Csorba
BACKGROUND: Until about 2010, people who inject drugs (PWIDs) injected almost exclusively heroin and amphetamines in Hungary. After 2010, self-reported studies have indicated a dominance of new psychoactive substances on the drug market for injectable drugs. METHODS: Between March 2015 and February 2016, we collected used and discarded injecting paraphernalia. We utilized chemical analysis to assess and UCINet to visualize the connections between the most prevalent main substances and their respective co-occurring additional components at 7 locations in Hungary...
June 16, 2017: International Journal on Drug Policy
https://www.readbyqxmd.com/read/28628687/the-infatuation-with-biotin-supplementation-is-there-truth-behind-its-rising-popularity-a-comparative-analysis-of-clinical-efficacy-versus-social-popularity
#10
Teo Soleymani, Kristen Lo Sicco, Jerry Shapiro
<p>Biotin, also known as Vitamin B7 or vitamin H, is a water-soluble B vitamin that acts as an essential cofactor for several carboxylases involved in the cellular metabolism of fatty acids, amino acids, and gluconeogenesis. Although there exists an incredible amount of social media hype and market advertising touting its efficacy for the improvement of hair quantity and quality, biotin's efficacy for hair remains largely unsubstantiated in scientific literature. We reviewed all pertinent scientific literature regarding the efficacy of biotin supplementation for hair growth and quality improvement, and we also investigated its popularity in society defined as a function of market analytics...
May 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28627961/microsomal-prostaglandin-e2-synthase-1-inhibitors-a-patent-review
#11
Anastasia Psarra, Aikaterini Nikolaou, Maroula G Kokotou, Dimitris Limnios, George Kokotos
Microsomal prostaglandin E2 synthase-1 (mPGES-1) catalyzes the terminal step of prostaglandin E2 (PGE2) generation. It is strongly upregulated in inflamed tissues and overexpressed in tumors and it has been recognized as a key enzyme in inflammatory diseases such as arthritis, atherosclerosis, stroke and cancer. Thus, a great effort has been devoted in developing synthetic mPGES-1 inhibitors as novel anti-inflammatory agents. Areas covered: This review article summarizes the mPGES-1 inhibitors presented in patent literature from 2000 to August 2016 and their biological evaluation, discussing their activities in vitro and in vivo...
June 19, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28627937/the-safety-of-intra-articular-injections-for-the-treatment-of-knee-osteoarthritis-a-critical-narrative-review
#12
Christelle Nguyen, François Rannou
International guidelines recommend that the management of knee osteoarthritis (OA) combine both nonpharmacological and pharmacological interventions. Intra-articular (IA) therapies are considered part of this multimodal approach and are well-established Food and Drug Administration (FDA) and European Medicines Agency (EMA)-approved treatments. Areas covered. Safety data for knee OA, including IA corticosteroids, hyaluronic acid, platelet-rich plasma and botulinum toxin are critically reviewed, and evidence- and pratice-based measures to improve safety of IA therapies are discussed...
June 19, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28627808/evaluation-of-a-pharmaceutical-risk-sharing-agreement-when-patients-are-screened-for-the-probability-of-success
#13
Reza Mahjoub, Fredrik Ødegaard, Gregory S Zaric
We analyze a game-theoretic model of a risk-sharing agreement between a payer and a pharmaceutical firm. The drug manufacturer chooses the price while the payer sets the rebate rate and decides which patients are eligible for treatment. The manufacturer provides the payer with a rebate for nonresponding patients. We generalize on the existing literature, by making both price and rebate rate decision variables, allowing the rebate rate to be different from 100%, and incorporating 2 types of administrative costs...
June 19, 2017: Health Economics
https://www.readbyqxmd.com/read/28627268/the-significance-of-drug-to-lipid-ratio-to-the-development-of-optimized-liposomal-formulation
#14
Maria Chountoulesi, Nikolaos Naziris, Natassa Pippa, Costas Demetzos
Liposomes are considered to be one of the most extensively investigated drug delivery nanosystems. Each drug can be loaded either in the liposomal hydrophilic core or within the lipidic bilayer and delivered eventually to the proper site into the organism. There are already many marketed approved liposomal products. The development of a liposomal product is a quite complicated process, while many critical parameters have to be investigated during the preparation process. The present study deals with the drug-to-lipid ratio (D/L ratio), which is a critical process parameter, expresses the actual capacity of the liposome to accommodate the drug and can play a key role at the optimization of every liposomal formulation...
June 18, 2017: Journal of Liposome Research
https://www.readbyqxmd.com/read/28625973/prevalence-and-correlates-of-electronic-cigarette-use-among-canadian-students-cross-sectional-findings-from-the-2014-15-canadian-student-tobacco-alcohol-and-drugs-survey
#15
Annie Montreuil, Marjorie MacDonald, Mark Asbridge, T Cameron Wild, David Hammond, Steve Manske, Erin Rutherford
BACKGROUND: Over the past decade, youth tobacco use has declined, and electronic cigarettes (e-cigarettes) have entered the market. The aims of this study were to describe the prevalence of e-cigarette use among youth in Canada, by province, across sociodemographic variables and smoking-related correlates; and to examine associations among e-cigarette use, sociodemographic variables and smoking-related correlates, with adjustment for other factors. METHODS: The 2014/15 Canadian Student Tobacco, Alcohol and Drugs Survey, a biennial, school-based survey, was administered to students in grades 6-12 in all Canadian provinces...
June 14, 2017: CMAJ Open
https://www.readbyqxmd.com/read/28625144/detection-of-poor-quality-artemisinin-based-combination-therapy-act-medicines-marketed-in-benin-using-simple-and-advanced-analytical-techniques
#16
Achille Yemoa, Védaste Habyalimana, Jérémie K Mbinze, Victoria Crickboom, Benjamin Muhigirwa, Agnès Ngoya, Pierre-Yves Sacré, Fernand Gbaguidi, Joëlle Quetin-Leclercq, Philippe Hubert, Roland D Marini
BACKGROUND: Poor quality antimalarial medicines still represent a threat to the public health, especially in Sub-Saharan Africa who bears a disproportionate share of the global burden of malaria. It is essential and urgent to strengthen mechanisms against counterfeit medicines. One of the approaches is regular market surveillance through quality controls. METHODS: 12 samples of artemether/lumefantrine were collected from formal and informal drug sellers in Cotonou (Benin) as well as additional other similar samples from Rwanda (13 samples) and from D...
June 15, 2017: Current Drug Safety
https://www.readbyqxmd.com/read/28625003/when-science-is-not-enough-a-framework-towards-more-customer-focused-drug-development
#17
REVIEW
Nektarios Oraiopoulos, William C N Dunlop
INTRODUCTION: The purpose of this study was to identify the key barriers to a customer-focused drug development process and develop a comprehensive framework to overcome them. METHODS: The paper draws on existing literature, both academic and practitioner, across a range of disciplines (innovation management, marketing, organizational behavior, behavioral economics, health economics, industry reports). On the basis of this extensive review, a conceptual framework is developed that offers concrete suggestions on how organizations can overcome the barriers and enable a more customer-focused development process...
June 17, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28624673/a-geographical-analysis-of-trafficking-on-a-popular-darknet-market
#18
Julian Broséus, Damien Rhumorbarbe, Marie Morelato, Ludovic Staehli, Quentin Rossy
Cryptomarkets are online marketplaces, located on the darknet, that facilitate the trading of a variety of illegal goods, mostly drugs. While the literature essentially focus on drugs, various other goods and products related to financial or identity fraud, firearms, counterfeit goods, as well as doping products are also offered on these marketplaces. Through the analysis of relevant data collected on a popular marketplace in 2014-2015, Evolution, this research provides an analysis of the structure of trafficking (types and proportions of products, number of vendors and shipping countries)...
June 4, 2017: Forensic Science International
https://www.readbyqxmd.com/read/28621572/changes-to-international-non-proprietary-names-for-antibody-therapeutics-2017-and-beyond-of-mice-men-and-more%C3%A2
#19
Paul W H I Parren, Paul J Carter, Andreas Plückthun
Active pharmaceutical substances require an International Nonproprietary Name (INN)assigned by the World Health Organization (WHO) to obtain market authorization as a medicinal product. INNsare selected to represent a unique, generic namefor a drug enablingunambiguous identification by stakeholders worldwide. INNs may be requested after initiating clinical development of an investigational drug. Pharmaceutical classes are indicated by a common stem or suffix. Currently, INNsfor monoclonal antibody-based drugs are recognized by the suffix, -mab,preceded by a source infixsuch as-xi- (chimeric),-zu- (humanized) or -u- (human) designating the species from which the antibody was derived...
June 16, 2017: MAbs
https://www.readbyqxmd.com/read/28620728/contents-of-heavy-metals-in-chinese-edible-herbs-evidence-from-a-case-study-of-epimedii-folium
#20
Xiao-Hua Yang, Hua-Feng Zhang, Li-Li Niu, Ying Wang, Jiang-Hua Lai
Toxic heavy metal contamination in Chinese edible herbs has raised a worldwide concern. In this study, heavy metals in Epimedii Folium, an edible medicinal plant in China, were quantitatively analyzed. Variations of heavy metals in different species, in various organs (i.e., leaves, stems, and roots), in wild-growing and cultivated plants, and in 35 market samples of Epimedii Folium, were systematically investigated. In all of Epimedium samples, Hg (mercury) was not detectable (0.00 μg/g). Four species, Epimedium pubescens, Epimedium sagittatum, Epimedium brevicornu, and Epimedium wushanense, were found to contain Cu (copper) and Pb (lead)...
June 16, 2017: Biological Trace Element Research
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