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Large biotechnology based initiatives, like the Human Genome Project, in addition to accelerating scientific progress and improving the understanding of basic biological process, are responsible for an increased demand for high quality drug candidates. In this regard, combinatorial libraries have become a subject of intense interest, as chemists and biologists attempt to generate large numbers of compounds that bind to the increasing number of newly discovered and potentially medically relevant proteins. Now that a variety of exploratory combinatorial chemistry efforts have been reported, it is appropriate to evaluate the utility of these procedures which have often outpaced conservative chemical characterization regarding composition and purity of products. The use of assay formats dictated by the needs of the synthetic protocol have also often circumvented disciplined evaluation of how relevant the assay data is to realistic drug‐target interactions. This commentary examines procedural details whereby commonly used combinatorial practices can generate less useful information than anticipated. Concrete, practical suggestions are made for using combinatorial chemistry in a more focused manner in lead generation and development, so that disappointing results can be avoided and the high potential of this technology more effectively realized. © 1995 Wiley‐Liss, Inc.
Drug Development Research – Wiley
Published: Aug 1, 1995
Keywords: chemistry; pharmaceutical; methods
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