Journal of medicinal and pharmaceutical chemistry 2011-07-28

Selectivity of kinase inhibitor fragments.

Paul Bamborough, Murray J Brown, John A Christopher, Chun-wa Chung, Geoff W Mellor

Index: J. Med. Chem. 54 , 5131-43, (2011)

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Abstract

A kinase-focused screening set of fragments has been assembled and has proved successful for the discovery of ligand-efficient hits against many targets. Here we present some of our general conclusions from this exercise. Notably, we present the first profiling results for literature fragments that have previously been used as starting points for optimization against individual kinases. We consider the importance of screening format and the extent to which selectivity is helpful in selecting fragments for progression. Results are also outlined for fragments targeting the DFG-out conformation and for atypical kinases such as PIM1 and lipid kinases.