A Novel Approach to Combinatorial Library Design

Author(s): Ramaswamy Nilakantan, Fred Immermann, Kevin Haraki

Journal Name: Combinatorial Chemistry & High Throughput Screening
Accelerated Technologies for Biotechnology, Bioassays, Medicinal Chemistry and Natural Products Research

Volume 5 , Issue 2 , 2002

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Abstract:

We address the problem of designing a general-purpose combinatorial library to screen for pharmaceutical leads. Conventional approaches focus on diversity as the primary factor in designing such libraries. We suggest making screening libraries out of a set of pharmaceutically relevant scaffolds, with multiple analogs per scaffold. The rationale for this rests on the fact that even though the hit-rate in active series is much higher than in the database as a whole, often a large fraction of the compounds in active series are inactive. This is especially true when the series has not been optimized for the target under study. We introduce the concept of ”hit-rate within a series“ and use historic screening data to arrive at a crude estimate for it. We then use simple probability arguments to show that 50-100 compounds are required in each series in order to be nearly certain of finding at least one active compound in each true active series for any given target.

Keywords: Combinatorial Library Design

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Article Details

VOLUME: 5
ISSUE: 2
Year: 2002
Page: [105 - 110]
Pages: 6
DOI: 10.2174/1386207024607310
Price: $65

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