keyword
MENU ▼
Read by QxMD icon Read
search

"Drug development"

keyword
https://www.readbyqxmd.com/read/28544095/phenotypic-assays-for-mycobacterium-tuberculosis-infection
#1
Ok-Ryul Song, Nathalie Deboosere, Vincent Delorme, Christophe J Queval, Gaspard Deloison, Elisabeth Werkmeister, Frank Lafont, Alain Baulard, Raffaella Iantomasi, Priscille Brodin
Tuberculosis (TB) is still a major global threat, killing more than one million persons each year. With the constant increase of Mycobacterium tuberculosis strains resistant to first- and second-line drugs, there is an urgent need for the development of new drugs to control the propagation of TB. Although screenings of small molecules on axenic M. tuberculosis cultures were successful for the identification of novel putative anti-TB drugs, new drugs in the development pipeline remains scarce. Host-directed therapy may represent an alternative for drug development against TB...
May 19, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28543601/influence-of-meals-and-glycemic-changes-on-qt-interval-dynamics
#2
Brenda Cirincione, Philip T Sager, Donald E Mager
Thorough QT/QTc studies have become an integral part of early drug development programs, with major clinical and regulatory implications. This analysis expands on existing pharmacodynamic models of QT interval analysis by incorporating the influence of glycemic changes on the QT interval in a semimechanistic manner. A total of 21 healthy subjects enrolled in an open-label phase 1 pilot study and provided continuous electrocardiogram monitoring and plasma glucose and insulin concentrations associated with a 24-hour baseline assessment...
May 22, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28543393/model-based-evaluation-of-exenatide-effects-on-the-qt-interval-in-healthy-subjects-following-continuous-iv-infusion
#3
Brenda Cirincione, Frank LaCreta, Philip Sager, Donald E Mager
Investigation of the cardiovascular proarrhythmic potential of a new chemical entity is now an integral part of drug development. Studies suggest that meals and glycemic changes can influence QT intervals, and a semimechanistic model has been developed that incorporates the effects of changes in glucose concentrations on heart rate (HR) and QT intervals. This analysis aimed to adapt the glucose-HR-QT model to incorporate the effects of exenatide, a drug that reduces postprandial increases in glucose concentrations...
May 22, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28541222/drug-target-prediction-by-multi-view-low-rank-embedding
#4
Limin Li, Menglan Cai
Drug repositioning has been a key problem in drug development, and heterogeneous data sources are used to predict drug-target interactions by different approaches. However, most of studies focus on a single representation of drugs or proteins. It has been shown that integrating multi-view representations of drugs and proteins can strengthen the prediction ability. For example, a drug can be represented by its chemical structure, or by its chemical response in different cells. A protein can be represented by its sequence, or by its gene expression values in different cells...
May 18, 2017: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/28541090/sixty-years-of-placebo-controlled-antipsychotic-drug-trials-in-acute-schizophrenia-systematic-review-bayesian-meta-analysis-and-meta-regression-of-efficacy-predictors
#5
Stefan Leucht, Claudia Leucht, Maximilian Huhn, Anna Chaimani, Dimitris Mavridis, Bartosz Helfer, Myrto Samara, Matteo Rabaioli, Susanne Bächer, Andrea Cipriani, John R Geddes, Georgia Salanti, John M Davis
OBJECTIVE: Antipsychotic drug efficacy may have decreased over recent decades. The authors present a meta-analysis of all placebo-controlled trials in patients with acute exacerbations of schizophrenia, and they investigate which trial characteristics have changed over the years and which are moderators of drug-placebo efficacy differences. METHOD: The search included multiple electronic databases. The outcomes were overall efficacy (primary outcome); responder and dropout rates; positive, negative, and depressive symptoms; quality of life; functioning; and major side effects...
May 25, 2017: American Journal of Psychiatry
https://www.readbyqxmd.com/read/28540603/positioning-novel-biologicals-in-ckd-mineral-and-bone-disorders
#6
REVIEW
Lida Tartaglione, Marzia Pasquali, Silverio Rotondi, Maria Luisa Muci, Adrian Covic, Sandro Mazzaferro
Renal osteodystrophy (ROD), the histologic bone lesions of chronic kidney disease (CKD), is now included in a wider syndrome with laboratory abnormalities of mineral metabolism and extra-skeletal calcifications or CKD-mineral and bone disorders (CKD-MBD), to highlight the increased burden of mortality. Aging people, frequently identified as early CKD, could suffer from either the classical age-related osteoporosis (OP) or ROD. Distinguishing between these two bone diseases may not be easy without bone biopsy...
May 24, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28539608/development-and-validation-of-a-high-throughput-whole-blood-thrombolysis-plate-assay
#7
T Bonnard, L S Law, Z Tennant, C E Hagemeyer
The objective of this work was to develop a high throughput assay for testing in vitro the thrombolytic activity using citrated whole blood samples, and to overcome the limitations of currently available techniques. We successfully developed a method that involves forming halo shaped, tissue factor induced, whole blood clots in 96 well plates, and then precisely measuring the thrombolysis process with a spectrophotometer plate reader. We here describe the implementation of this novel method, which we refer to as halo assay, and its validation with plasmin, urokinase and tissue plasminogen activator at different doses...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536367/a-brief-review-of-the-pharmacology-of-amitriptyline-and-clinical-outcomes-in-treating-fibromyalgia
#8
REVIEW
Kim Lawson
Fibromyalgia is a complex chronic condition characterized by pain, physical fatigue, sleep disorder and cognitive impairment. Evidence-based guidelines recommend antidepressants as treatments of fibromyalgia where tricyclics are often considered to have the greatest efficacy, with amitriptyline often being a first-line treatment. Amitriptyline evokes a preferential reduction in pain and fatigue of fibromyalgia, and in the Fibromyalgia Impact Questionnaire (FIQ) score, which is a quality of life assessment. The multimodal profile of the mechanisms of action of amitriptyline include monoamine reuptake inhibition, receptor modulation and ion channel modulation...
May 17, 2017: Biomedicines
https://www.readbyqxmd.com/read/28536050/a-systematic-reactor-design-approach-for-the-synthesis-of-active-pharmaceutical-ingredients
#9
Victor N Emenike, René Schenkendorf, Ulrike Krewer
Today's highly competitive pharmaceutical industry is in dire need of an accelerated transition from the drug development phase to the drug production phase. At the heart of this transition are chemical reactors that facilitate the synthesis of active pharmaceutical ingredients (APIs) and whose design can affect subsequent processing steps. Inspired by this challenge, we present a model-based approach for systematic reactor design. The proposed concept is based on the elementary process functions (EPF) methodology to select an optimal reactor configuration from existing state-of-the-art reactor types or can possibly lead to the design of novel reactors...
May 20, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28535992/impact-of-pharmacokinetic-pharmacodynamic-modelling-in-early-clinical-drug-development
#10
Jasper Dingemanse, Andreas Krause
Early clinical pharmacology studies in healthy subjects are often dissociated from patient studies. In this review we encourage the use of modelling and simulation techniques to generate valuable information at an early stage of clinical development. We illustrate these principles by presenting 5 different case studies from a spectrum of therapeutic drug classes. Their application leads to a better understanding of drug characteristics early on, thereby facilitating the design of dose-finding studies in the target patient population and saving resources...
May 20, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28534756/opportunities-for-data-science-in-the-pharmaceutical-industry-the-use-of-data-to-find-efficiencies-in-drug-development-can-t-come-too-soon
#11
Nirmal Keshava
By the numbers, 2016 was not a good year for the U.S. pharmaceutical industry. As of early December, only 19 new drugs had been approved by the Food and Drug Administration (FDA), fewer than half of those approved in 2015 and the lowest number since 2007. Further, the FDA approved only 61% of submissions in 2016, compared to 95% in 2015 [1]. And, among the largest companies, the return on investment for research and development (R&D) fell to 3.7% [2].
May 2017: IEEE Pulse
https://www.readbyqxmd.com/read/28534432/gastrointestinal-microphysiological-systems
#12
Sarah E Blutt, James R Broughman, Winnie Zou, Xi-Lei Zeng, Umesh C Karandikar, Julie In, Nicholas C Zachos, Olga Kovbasnjuk, Mark Donowitz, Mary K Estes
Gastrointestinal diseases are a significant health care and economic burden. Prevention and treatment of these diseases have been limited by the available human biologic models. Microphysiological systems comprise organ-specific human cultures that recapitulate many structural, biological, and functional properties of the organ in smaller scale including aspects of flow, shear stress and chemical gradients. The development of intestinal microphysiological system platforms represents a critical component in improving our understanding, prevention, and treatment of gastrointestinal diseases...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28534338/-application-and-development-of-patient-derived-tumor-xenograft-model-in-translational-medicine-of-tumor
#13
Zhenqiang Wang, Zhenggang Zhu
Development of novel drugs is an integral part of the translational medicine in the field of cancer research, and the construction and application of preclinical animal models play vital roles in drugs development. Patient-derived tumor xenograft models (PDX) have been shown to be more accurate in prediction of clinical outcomes of novel drugs and are being used for preclinical drug evaluation based on the fact that PDX models mostly retain the principal histologic and genetic characteristics of their donor tumor...
May 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28534261/the-role-of-drug-metabolites-in-the-inhibition-of-cytochrome-p450-enzymes
#14
Momir Mikov, Maja Đanić, Nebojša Pavlović, Bojan Stanimirov, Svetlana Goločorbin-Kon, Karmen Stankov, Hani Al-Salami
Following the drug administration, patients are exposed not only to the parent drug itself, but also to the metabolites generated by drug-metabolizing enzymes. The role of drug metabolites in cytochrome P450 (CYP) inhibition and subsequent drug-drug interactions (DDIs) have recently become a topic of considerable interest and scientific debate. The list of metabolites that were found to significantly contribute to clinically relevant DDIs is constantly being expanded and reported in the literature. New strategies have been developed for better understanding how different metabolites of a drug candidate contribute to its pharmacokinetic properties and pharmacological as well as its toxicological effects...
May 22, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28533246/5-aminopyrazole-4-carboxamide-based-compounds-prevent-the-growth-of-cryptosporidium-parvum
#15
Wenlin Huang, Ryan Choi, Matthew A Hulverson, Zhongsheng Zhang, Molly C McCloskey, Deborah A Schaefer, Grant R Whitman, Lynn K Barrett, Rama Subba Rao Vidadala, Michael W Riggs, Dustin J Maly, Wesley C Van Voorhis, Kayode K Ojo, Erkang Fan
Cryptosporidium parvum calcium-dependent protein kinase 1 (CpCDPK1) is a promising target for drug development against cryptosporidiosis. We report a series of low nanomolar CpCDPK1 5-aminopyrazole-4-carboxamide (AC) scaffold inhibitors that also potently inhibit C. parvum growth in vitro Correlation between anti-CpCDPK1 and C. parvum growth inhibition, as previously reported for pyrazolopyrimidines, was not apparent. Nonetheless, lead AC-compounds exhibited a substantial reduction of parasite burden in the neonatal mouse cryptosporidiosis model when dosed at 25 mg/kg...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533219/obesity-linked-phosphorylation-of-sirt1-by-ck2-inhibits-its-nuclear-localization-and-promotes-fatty-liver
#16
Sung E Choi, Sanghoon Kwon, Sunmi Seok, Zhen Xiao, Kwan-Woo Lee, Yup Kang, Xiaoling Li, Kosaku Shinoda, Shingo Kajimura, Byron Kemper, Jongsook Kim Kemper
Sirtuin1 (SIRT1) deacetylase delays and improves many obesity-related diseases, including non-alcoholic fatty liver disease (NAFLD) and diabetes, and has received great attention as a drug target. SIRT1 function is aberrantly low in obesity, so understanding the underlying mechanisms is important for drug development. Here, we show that obesity-linked phosphorylation of SIRT1 inhibits its function and promotes pathological symptoms of NAFLD. In proteomic analysis, Ser-164 was identified as a major serine phosphorylation site in SIRT1 in obese, but not lean, mice, and this phosphorylation was catalyzed by casein kinase-2 (CK2), the levels of which were dramatically elevated in obesity...
May 22, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28533120/evaluation-of-new-chemical-entities-as-substrates-of-liver-transporters-in-the-pharmaceutical-industry-response-to-regulatory-requirements-and-future-steps
#17
Noriko Okudaira
This article discusses the evaluation of drug candidates as hepatic transporter substrates. Recently, research on the applications of hepatic transporters in the pharmaceutical industry has improved to meet the requirements of the regulatory guidelines for the evaluation of drug interactions. To identify the risk of transporter-mediated drug-drug interactions (DDIs) at an early stage of drug development, we employed a strategy of reviewing the in vivo animal pharmacokinetics and tissue distribution data obtained in the discovery stage together with the in vitro data obtained for regulatory submission...
May 19, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28532202/experiences-of-establishing-an-academic-early-phase-clinical-trials-unit
#18
Sarah R Brown, Debbie Sherratt, Gill Booth, Julia Brown, Fiona Collinson, Walter Gregory, Louise Flanagan
BACKGROUND: Early phase trials are essential in drug development, determining appropriate dose levels and assessing preliminary activity. These trials are undertaken by industry and academia, with increasing collaborations between the two. There is pressure to perform these trials quickly, safely, and robustly. However, there are inherent differences between developing and managing early phase, compared to late phase, drug trials. This article describes an approach to establishing an academically led early phase trial portfolio, highlighting lessons learned and sharing experiences...
May 1, 2017: Clinical Trials: Journal of the Society for Clinical Trials
https://www.readbyqxmd.com/read/28531943/recent-trends-in-zikv-research-a-step-away-from-cure
#19
REVIEW
Aftab Alam, Nikhat Imam, Anam Farooqui, Shahnawaz Ali, Md Zubbair Malik, Romana Ishrat
Zika virus (ZikV) is a member of the Flaviviridae virus family, genus Flavivirus has emerged as a potential threat to human health worldwide. Consequences of vertical infections includes microcephaly with brain and eye anomalies, and adult infections includes Guillain-Barrésyndrome (GBS), brain ischemia, myelitis and meningoencephalitis. To develop a better treatment, many efforts are being made, like drug-repurposing concept for FDA-approved drugs for antiviral activity are screened against ZikV infection and emerging as a promising alternative to expedite drug development and various vaccines like DNA, ZPIV, LAIV, mRNA and AGS-v vaccines have been designed and in under clinical trial phases...
May 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28531912/from-bench-to-market-preparing-human-pluripotent-stem-cells-derived-cardiomyocytes-for-various-applications
#20
REVIEW
Sung-Hwan Moon, Daekyeong Bae, Taek-Hee Jung, Eun-Bin Chung, Young-Hoon Jeong, Soon-Jung Park, Hyung-Min Chung
Human cardiomyocytes (CMs) cease to proliferate and remain terminally differentiated thereafter, when humans reach the mid-20s. Thus, any damages sustained by myocardium tissue are irreversible, and they require medical interventions to regain functionality. To date, new surgical procedures and drugs have been developed, albeit with limited success, to treat various heart diseases including myocardial infarction. Hence, there is a pressing need to develop more effective treatment methods to address the increasing mortality rate of the heart diseases...
May 30, 2017: International Journal of Stem Cells
keyword
keyword
47312
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"