Analysis of Chemical Space

Chapter Details

Pub Date: 1 Oct 2002
Pages: 36
Chapter Category: Drug Design
Taken from the Book: Adaptive Systems in Drug Design
Book Series: Intelligence Unit
Edited by: Gisbert Schneider and Sung-Sau So

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Analysis of Chemical Space

Gisbert Schneider

About this Chapter

A main goal of virtual screening is to select activity-enriched sets of molecules — or single molecules exhibiting desired activity—from the space of all synthetically accessible structures. Currently the most advanced HTS techniques allow for testing of ~105 compounds per day, and a typical corporate screening library contains several hundred thousand samples. Although these facts alone represent a technological revolution, the turnover numbers still are extremely small compared with the total size of chemical space.1 As a consequence, even ultra HTS combined with fast, parallel combinatorial chemistry can only be successful if a reasonable pre-selection of molecules (or molecular building blocks) for screening is done. Otherwise this approach will more or less represent a random search with a very small probability of success. While HTS and ultraHTS have made significant progress in recent years, we should bear in mind that it will be very costly to screen a million of compounds for activity in all the new receptor assays (estimated $0.1 to $10 per compound per screen). Even if a company has these resources, it is rare that they have access to a diverse one-million-compound screening library. Thus it can be advantageous to integrate VS tools into the drug discovery process to find leads with novel scaffolds by either starting from competitor compounds described in the literature and/or from a proprietary, existing scaffold. Once a reliable VS process has been defined it can save resources and limit experimental efforts by suggesting defined sets of molecules.

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