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"Drug development"

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https://www.readbyqxmd.com/read/28732306/photostability-testing-using-online-reactor-hplc-hyphenation-and-mass-spectrometric-compound-identification-illustrated-by-ketoprofen-as-model-compound
#1
Jaber Assaf, Diego Zulkiewicz Gomes, Bernhard Wuest, Maria Kristina Parr
Investigations on the photochemical stability of pharmaceutical substances are mandatory in drug development and licensing as photo-induced degradation of an active pharmaceutical ingredient (API) may not only lead to decreased API concentrations but also to toxic or reactive products. Thus, the US Food and Drug Administration (FDA) and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) issued Guidance for Industry Q1B "Photostability Testing of New Drug Substances and Products" for testing of pure but also packed drugs...
July 8, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28732198/primary-cell-phenotypic-screening-illuminates-adrs-and-aops
#2
Audrey J Bone, Keith A Houck
Preclinical, in vitro screening for adverse drug reactions continues to present challenges in the field of drug development. In this issue of Cell Chemical Biology, Shah et al. (2017) employ a phenotypic screening strategy using a panel of human primary cells to define a signature response and an adverse outcome pathway for delayed type IV skin hypersensitivity.
July 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28731526/drug-discovery-and-development-for-rare-genetic-disorders
#3
REVIEW
Wei Sun, Wei Zheng, Anton Simeonov
Approximately 7,000 rare diseases affect millions of individuals in the United States. Although rare diseases taken together have an enormous impact, there is a significant gap between basic research and clinical interventions. Opportunities now exist to accelerate drug development for the treatment of rare diseases. Disease foundations and research centers worldwide focus on better understanding rare disorders. Here, the state-of-the-art drug discovery strategies for small molecules and biological approaches for orphan diseases are reviewed...
July 21, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28730966/nicotinic-cholinergic-system-in-the-hypothalamus-modulates-the-activity-of-the-hypothalamic-neuropeptides-during-the-stress-resp
#4
Burcu Balkan, Sakire Pogun
The hypothalamus harbors high levels of cholinergic neurons and axon terminals. Nicotinic acetylcholine receptors, which play an important role in cholinergic neurotransmission, are expressed abundantly in the hypothalamus. Accumulating evidence reveals a regulatory role for nicotine in diverse functions mediated by the hypothalamus, including the regulation of the stress responses. The nicotinic cholinergic system lies at the intersection of homeostatic and reward pathways and shows sex differences in some of its effects...
July 19, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28730936/an-industry-update-what-is-the-latest-news-in-therapeutic-delivery
#5
Iain Simpson
This Industry Update covers the period from 1 through 30 April 2017, and is based on information sourced from company press releases, scientific literature, patents and various news websites. Biogen expanded its portfolio of developmental drugs targeting neurological diseases by licensing a drug from Bristol-Myers Squibb which is currently under investigation for the treatment of progressive supranuclear palsy. Takeda announced a deal with NuBiyota focused on developing treatments for gastrointestinal disorders, based on the manipulation of microbes living in the gut...
July 2017: Therapeutic Delivery
https://www.readbyqxmd.com/read/28730718/impact-of-binding-mechanism-on-selective-inhibition-of-histone-deacetylase-isoforms
#6
Christian Meyners, Franz-Josef Meyer-Almes
Industrialized drug screening campaigns usually deliver hundreds of compounds that are active on a particular pharmaceutical target. In light of high failure rates of drug candidates due to unforeseeable off-target toxicity, the early identification of the most promising compounds with high potential for target selectivity is an urgent need to improve the quality of lead compounds and lower attrition rates in the drug development process. The reliable prediction of the selectivity of active substances for a target protein is a challenging task...
June 14, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28730565/landmark-and-longitudinal-exposure-response-analyses-in-drug-development
#7
Chuanpu Hu, Honghui Zhou, Amarnath Sharma
No abstract text is available yet for this article.
July 20, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28729650/large-scale-analysis-of-drug-side-effects-via-complex-regulatory-modules-composed-of-micrornas-transcription-factors-and-gene-sets
#8
Xiaodong Jia, Qing Jin, Xiangqiong Liu, Xiusen Bian, Yunfeng Wang, Lei Liu, Hongzhe Ma, Fujian Tan, Mingliang Gu, Xiujie Chen
Identifying the occurrence mechanism of drug-induced side effects (SEs) is critical for design of drug target and new drug development. The expression of genes in biological processes is regulated by transcription factors(TFs) and/or microRNAs. Most of previous studies were focused on a single level of gene or gene sets, while studies about regulatory relationships of TFs, miRNAs and biological processes are very rare. Discovering the complex regulating relations among TFs, gene sets and miRNAs will be helpful for researchers to get a more comprehensive understanding about the mechanism of side reaction...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28728898/kbe009-an-antimalarial-bestatin-like-inhibitor-of-the-plasmodium-falciparum-m1-aminopeptidase-discovered-in-an-ugi-multicomponent-reaction-derived-peptidomimetic-library
#9
Jorge González-Bacerio, Sarah El Chamy Maluf, Yanira Méndez, Isel Pascual, Isabelle Florent, Pollyana M S Melo, Alexandre Budu, Juliana C Ferreira, Ernesto Moreno, Adriana K Carmona, Daniel G Rivera, Maday Alonso Del Rivero, Marcos L Gazarini
Malaria is a global human parasitic disease mainly caused by the protozoon Plasmodium falciparum. Increased parasite resistance to current drugs determines the relevance of finding new treatments against new targets. A novel target is the M1 alanyl-aminopeptidase from P. falciparum (PfA-M1), which is essential for parasite development in human erythrocytes and is inhibited by the pseudo-peptide bestatin. In this work, we used a combinatorial multicomponent approach to produce a library of peptidomimetics and screened it for the inhibition of recombinant PfA-M1 (rPfA-M1) and the in vitro growth of P...
July 4, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28725871/new-anthrarobin-acyl-derivatives-as-butyrylcholinesterase-inhibitors-synthesis-in-vitro-and-in-silico-studies
#10
Mehreen Lateef, Abid Azhar, Bina S Siddiqui, Shamshad Zarina, Nizam Uddin, Muhammad F Anwar, Kauser Siddiqui, Kaniz F Azhar, Lubna Iqbal, Rashad Mehmood, Shagufta Perveen
To treat Alzheimer's disease (AD), the available candidates are effective only against mild AD or have side effects. So, a study was planned to synthesis new candidates that may have good potential to treat AD. A series of new anthrarobin acyl derivatives (2-8) were synthesized by the reaction of anthrarobin (1) and acetic anhydride/acyl chlorides. The product were characterized by (1)H NMR and EI-MS, and evaluated for butyrylcholinesterase (BuChE) inhibition activity. Compounds 5 and 4 showed notable BuChE inhibitory potential with IC50 5...
July 2017: Heliyon
https://www.readbyqxmd.com/read/28725482/systems-biology-driving-drug-development-from-design-to-the-clinical-testing-of-the-anti-erbb3-antibody-seribantumab-mm-121
#11
REVIEW
Birgit Schoeberl, Art Kudla, Kristina Masson, Ashish Kalra, Michael Curley, Gregory Finn, Emily Pace, Brian Harms, Jaeyeon Kim, Jeff Kearns, Aaron Fulgham, Olga Burenkova, Viara Grantcharova, Defne Yarar, Violette Paragas, Jonathan Fitzgerald, Marisa Wainszelbaum, Kip West, Sara Mathews, Rachel Nering, Bambang Adiwijaya, Gabriela Garcia, Bill Kubasek, Victor Moyo, Akos Czibere, Ulrik B Nielsen, Gavin MacBeath
The ErbB family of receptor tyrosine kinases comprises four members: epidermal growth factor receptor (EGFR/ErbB1), human EGFR 2 (HER2/ErbB2), ErbB3/HER3, and ErbB4/HER4. The first two members of this family, EGFR and HER2, have been implicated in tumorigenesis and cancer progression for several decades, and numerous drugs have now been approved that target these two proteins. Less attention, however, has been paid to the role of this family in mediating cancer cell survival and drug tolerance. To better understand the complex signal transduction network triggered by the ErbB receptor family, we built a computational model that quantitatively captures the dynamics of ErbB signaling...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28725194/sophisticated-cloning-fermentation-and-purification-technologies-for-an-enhanced-therapeutic-protein-production-a-review
#12
REVIEW
Sanjeev K Gupta, Pratyoosh Shukla
The protein productions strategies are crucial towards the development of application based research and elucidating the novel purification strategies for industrial production. Currently, there are few innovative avenues are studies for cloning, upstream, and purification through efficient bioprocess development. Such strategies are beneficial for industries as well as proven to be vital for effectual therapeutic protein development. Though, these techniques are well documented, but, there is scope of addition to current knowledge with novel and new approaches and it will pave new avenues in production of recombinant microbial and non-microbial proteins including secondary metabolites...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28724415/identification-and-characterization-of-the-antiplasmodial-activity-of-hsp90-inhibitors
#13
Claribel Murillo-Solano, Chunmin Dong, Cecilia G Sanchez, Juan C Pizarro
BACKGROUND: The recent reduction in mortality due to malaria is being threatened by the appearance of Plasmodium falciparum parasites that are resistant to artemisinin in Southeast Asia. To limit the impact of resistant parasites and their spread across the world, there is a need to validate anti-malarial drug targets and identify new leads that will serve as foundations for future drug development programmes targeting malaria. Towards that end, the antiplasmodial potential of several Hsp90 inhibitors was characterized...
July 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28723506/biomarkers-for-metastatic-castration-resistant-prostate-cancer-mcrpc-yes-or-no-predictive-and-response-biomarkers-towards-precision-medicine-in-mcrpc
#14
Joaquin Mateo
Advances in drug development and molecular studies for castration-resistant prostate cancer (CRPC) render the possibility of more efficient and precise patient care through the use of predictive, response, and resistance biomarkers. Thorough scrutiny of assay validation and clinical qualification processes for biomarkers in development, ideally in parallel with clinical trials, is critical for the success of personalised medicine in CRPC management.
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28722440/life-under-the-microscope-quantifying-live-cell-interactions-to-improve-nanoscale-drug-delivery
#15
Angus P R Johnston
The behavior of cells and how they react to stimuli is critically important for drug development, drug delivery, and understanding the molecular basis of many diseases. However, we still lack a comprehensive understanding of these interactions, particularly in relation to drug delivery from nanoparticles. This Sensors Issues article discusses the importance of quantifying these interactions and highlights some key areas where advances in sensor technology have the potential to transform our understanding of drug delivery and cell biology...
January 27, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28722322/advanced-methods-for-dose-and-regimen-finding-during-drug-development-summary-of-the-ema-efpia-workshop-on-dose-finding-london-4-5-december-2014
#16
F T Musuamba, E Manolis, N Holford, Sya Cheung, L E Friberg, K Ogungbenro, M Posch, Jwt Yates, S Berry, N Thomas, S Corriol-Rohou, B Bornkamp, F Bretz, A C Hooker, P H Van der Graaf, J F Standing, J Hay, S Cole, V Gigante, K Karlsson, T Dumortier, N Benda, F Serone, S Das, A Brochot, F Ehmann, R Hemmings, I Skottheim Rusten
Inadequate dose selection for confirmatory trials is currently still one of the most challenging issues in drug development, as illustrated by high rates of late-stage attritions in clinical development and postmarketing commitments required by regulatory institutions. In an effort to shift the current paradigm in dose and regimen selection and highlight the availability and usefulness of well-established and regulatory-acceptable methods, the European Medicines Agency (EMA) in collaboration with the European Federation of Pharmaceutical Industries Association (EFPIA) hosted a multistakeholder workshop on dose finding (London 4-5 December 2014)...
July 19, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28721009/patient-profiles-and-clinical-utility-of-mepolizumab-in-severe-eosinophilic-asthma
#17
REVIEW
Pranabashis Haldar
Mepolizumab (Nucala(®)) is an effective and specific anti-eosinophil molecular therapy that has recently been approved as add-on therapy for the management of severe eosinophilic asthma by the US Food and Drug Administration (FDA), European Medicines Agency (EMA; European Union) and more recently National Institute for Health and Care Excellence (NICE; UK). It is one of several molecular therapies in development for this indication and is illustrative of the strategic trajectory for pharmaceutical drug development taken over the past decade in several disease areas...
2017: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/28720135/exploring-anti-malarial-potential-of-fda-approved-drugs-an-in-silico-approach
#18
Gayatri Ramakrishnan, Nagasuma Chandra, Narayanaswamy Srinivasan
BACKGROUND: The critically important issue on emergence of drug-resistant malarial parasites is compounded by cross resistance, where resistance to one drug confers resistance to other chemically similar drugs or those that share mode of action. This aspect requires discovery of new anti-malarial compounds or formulation of new combination therapy. The current study attempts to contribute towards accelerating anti-malarial drug development efforts, by exploring the potential of existing FDA-approved drugs to target proteins of Plasmodium falciparum...
July 18, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28720059/cervical-cancer-cell-derived-angiopoietins-promote-tumor-progression
#19
Ping Yang, Na Chen, Dongyun Yang, Janet Crane, Bangxing Huang, Ruiqing Dong, Xiaoqing Yi, Jing Guo, Jing Cai, Zehua Wang
Metastatic or recurrent cervical cancer has limited treatment options and a high rate of mortality. Although anti-vascular endothelial growth factor drugs have shown great promise as a therapeutic target for treatment of advanced cervical cancer, drug resistance and class-specific side effects negate long-term benefits. The identification of alternative anti-angiogenic factors will be critical for future drug development for advanced or recurrent cervical cancer. In this study, we found that angiopoietins and Tie receptors were highly expressed in cervical cancer cells...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28719360/alzheimer-s-disease-dawn-of-a-new-era
#20
Farideh Amirrad, Emira Bousoik, Kiumars Shamloo, Hassan Al-Shiyab, Viet-Huong V Nguyen, Hamidreza Montazeri Aliabadi
Alzheimer's disease (AD) is an irreversible neurodegenerative disease characterized by a progressive decline in cognition and memory, leading to significant impairment in daily activities and ultimately death. It is the most common cause of dementia, the prevalence of which increases with age; however, age is not the only predisposing factor. The pathology of this cognitive impairing disease is still not completely understood, which has limited the development of valid therapeutic options. Recent years have witnessed a wide range of novel approaches to combat this disease, so that they greatly increased our understanding of the disease and of the unique drug development issues associated with this disease...
2017: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
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