Context-dependent cell cycle checkpoint abrogation by a novel kinase inhibitor.

ABSTRACT:

Background

Checkpoint kinase 1 and 2 (Chk1/Chk2), and the Aurora kinases play a critical role in the activation of the DNA damage response and mitotic spindle checkpoints. We have identified a novel inhibitor of these kinases and utilized this molecule to probe the functional interplay between these two checkpoints.

Principal findings

Fragment screening, structure guided design, and kinase cross screening resulted in the identification of a novel, potent small molecule kinase inhibitor (VER-150548) of Chk1 and Chk2 kinases with IC(50)s of 35 and 34 nM as well as the Aurora A and Aurora B kinases with IC(50)s of 101 and 38 nM. The structural rationale for this kinase specificity could be clearly elucidated through the X-ray crystal structure. In human carcinoma cells, VER-150

SUBMITTER: Massey AJ 

PROVIDER: S-EPMC2956624 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature