Virtual screening for kinase inhibitors


Paul D. Lyne, Cancer Discovery, Cancer Discovery, AstraZeneca, 35 Gatehouse Drive, Waltham, MA 02451
A virtual screen of a subsection of our corporate collection was performed for checkpoint-1 kinase using a knowledge-based strategy. This involved initial filtering of the compound collection by application of generic physical properties followed by removal of compounds with undesirable functionality. Subsequently a 3-D pharmacophore screen for compounds with a kinase binding motif was applied. The remaining compounds were docked and rescored, resulting in 103 compounds being tested. This yielded 36 hits in the IC50 range of 110nM to 68uM, corresponding to four chemical classes.