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- Volume 13, Issue 2, 2010
Combinatorial Chemistry & High Throughput Screening - Volume 13, Issue 2, 2010
Volume 13, Issue 2, 2010
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Editorial [Hot topic: Preclinical Profiling in Drug Discovery (Guest Editor: Larry C. Wienkers)]
More LessThe nomination of a lead discovery molecule to a viable drug candidate is a key step in the drug discovery/development continuum. Transition through this critical milestone requires the knowledge of the pharmacological action as well as insights into the absorption, distribution, metabolism, excretion and toxicity (ADMET) profile of the compound. The current motivation to balance the pharmacological attributes Read More
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Preformulation Designed to Enable Discovery and Assess Developability
More LessPhysicochemical properties of drug molecules impact many aspects of both in vivo and in vitro behavior. Poor physicochemical properties can often create a significant impediment to establishing reliable SAR, establishing proof of principle type studies using in vivo models, and eventually leading to added performance variability and costs throughout the development life cycle; in the worst case scenario, even preventing executio Read More
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Solubility and Permeability Measurement and Applications in Drug Discovery
Authors: Philip S. Burton and Jay T. GoodwinSolubility and cellular permeability are two of the most important biopharmaceutical properties impacting the successful development of drug substances. Given the importance of these properties, most pharmaceutical companies have invested in medium to high throughput technologies for early evaluation of these characteristics in the drug discovery funnel in order to select, prioritize or eliminate compounds with unfav Read More
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Evaluation of Drug Transporter Interactions in Drug Discovery and Development
Authors: Yurong Lai, Kathleen E. Sampson and Jeffrey C. StevensDrug transporters play an important role in the absorption, distribution, excretion and toxicity of both endogenous and exogenous compounds. Transporters may act as physiological ‘gatekeepers’ in the regulation of the pharmacological and/or toxicological effects of drugs by limiting distribution to tissues responsible for their effect and/or toxicity. This review will first provide a brief outline of the characteristics of mem Read More
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Enzyme Induction: Translating Multiple Approaches, Assays, Endpoints, and Opinions into a Valuable Induction Screening Strategy
Authors: Adrian Fretland and Mario MonshouwerDrug metabolizing enzyme induction, or the process of generating excess drug metabolizing enzyme in important tissues of drug disposition such as liver and intestine, can give rise to pharmacokinetic situations whereby drug interactions occur. There are two major concerns associated with enzyme induction. First is the potential loss of efficacy due to more rapid metabolism and second is the risk of an increase in the formati Read More
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Application of Cytochrome P450 Drug Interaction Screening in Drug Discovery
Authors: Robert S. Foti, Larry C. Wienkers and Jan L. WahlstromAdvances in drug interaction screening have resulted in reduced compound attrition rates due to unfavorable CYP-mediated drug interactions in clinical trials and improved patient safety. A major driver for the success in predicting drug interactions is a better understanding of the biological, chemical or mechanical factors that can impact the prediction of drug interactions in vitro. The enzyme source, probe substrate, access Read More
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Scaling In Vivo Pharmacokinetics from In Vitro Metabolic Stability Data in Drug Discovery
Authors: Wendy Klopf and Philip WorboysIn this review, the current approach to predicting hepatic clearance from in vitro metabolic systems is discussed along with a survey of current industry practice. The definitive method of determining intrinsic clearance remains the measurement of Michaelis-Menten parameters derived from metabolite formation rate data. However, in drug discovery this method has limitations which result in the method most commonly Read More
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Plasma Protein Binding in Drug Discovery and Development
Authors: Monique L. Howard, John J. Hill, Gerald R. Galluppi and Matthew A. McLeanThis review describes methods for quantifying the binding of small molecule drug candidates to plasma proteins and the application of these methods in drug discovery and development. Particular attention is devoted to methods amenable to medium-to-high throughput analysis and those well suited for measurement of compounds that are highly protein bound. The methods reviewed herein include the conventional Read More
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Building a Tiered Approach to In Vitro Predictive Toxicity Screening: A Focus on Assays with In Vivo Relevance
More LessOne of the greatest challenges facing the pharmaceutical industry today is the failure of promising new drug candidates due to unanticipated adverse effects discovered during preclinical animal safety studies and clinical trials. Late stage attrition increases the time required to bring a new drug to market, inflates development costs, and represents a major source of inefficiency in the drug discovery/development process. It Read More
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Application of In Vivo Animal Models to Characterize the Pharmacokinetic and Pharmacodynamic Properties of Drug Candidates in Discovery Settings
Authors: Benny M. Amore, John P. Gibbs and Maurice G. EmeryA goal of preclinical discovery is the identification of drug candidates suitable for clinical testing. Successful integration of in vitro and in vivo experimental data sets can afford projections of human dose regimens anticipated to be safe and therapeutically beneficial. While in vitro experiments guide new chemical syntheses and are essential to understanding drug action and disposition, in vivo characterizations pro Read More
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Meet the Guest Editor
More LessLarry C. Wienkers is currently the Executive Director for the Department of Pharmacokinetics and Drug Metabolism at Amgen in Seattle, WA. Larry's areas of scientific interest include: understanding of the mechanisms of cytochrome P450 oxidation reactions; the application of novel in vitro metabolism techniques to understand the enzymatic basis for biotransformation of potential therapeutic agents at the drug discov Read More
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Volumes & issues
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Volume 28 (2025)
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Volume 27 (2024)
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Volume 26 (2023)
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Volume 25 (2022)
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Volume 24 (2021)
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Volume 23 (2020)
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Volume 22 (2019)
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Volume 21 (2018)
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Volume 20 (2017)
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Volume 19 (2016)
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Volume 18 (2015)
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Volume 17 (2014)
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Volume 16 (2013)
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Volume 15 (2012)
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Volume 14 (2011)
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Volume 13 (2010)
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Volume 12 (2009)
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Volume 11 (2008)
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Volume 10 (2007)
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Volume 9 (2006)
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Volume 8 (2005)
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Volume 7 (2004)
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Volume 6 (2003)
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Volume 5 (2002)
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Volume 4 (2001)
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Volume 3 (2000)
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Label-Free Detection of Biomolecular Interactions Using BioLayer Interferometry for Kinetic Characterization
Authors: Joy Concepcion, Krista Witte, Charles Wartchow, Sae Choo, Danfeng Yao, Henrik Persson, Jing Wei, Pu Li, Bettina Heidecker, Weilei Ma, Ram Varma, Lian-She Zhao, Donald Perillat, Greg Carricato, Michael Recknor, Kevin Du, Huddee Ho, Tim Ellis, Juan Gamez, Michael Howes, Janette Phi-Wilson, Scott Lockard, Robert Zuk and Hong Tan
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