Searching for Chemokine Receptor Binding Antagonists by High Throughput Screening

Author:

Mellor Geoffrey W.1,Fogarty Simon J.1,O'Brien M. Shane1,Congreve Miles2,Banks Martyn N.1,Mills Kirsten M.1,Jefferies Barbara1,Houston John G.1

Affiliation:

1. Lead Discovery Unit, Glaxo Wellcome Research and Development (GW R&D), Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK

2. Exploratory Chemistry Unit, Glaxo Wellcome Research and Development (GW R&D), Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK

Abstract

Identification of putative drug candidates by high throughput screening is assuming enormous importance within the pharmaceutical industry, driven by increasing numbers of valid therapeutic targets from both classical and molecular biological sources. Screening is an applied discipline that requires equipment and, more importantly, thinking that is fundamentally different from more traditional, lower throughput assay methodology. This article describes the process as applied to the discovery of selective antagonists of three chemokine receptor binding systems, from the original biological targets to chemically prosecutable lead compounds, which are currently being investigated using traditional medicinal and combinatorial chemistry methods.

Publisher

Elsevier BV

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