CCT241533 is a selective inhibitor of checkpoint kinase 2 (Chk2; IC50 = 3 nM). In human cancer cell lines, CCT241533 blocks Chk2 activity and potentiates the cytotoxicity of the PARP inhibitors, rucaparib, AG-1447; and olaparib .
cct241533 inhibited chk2 with an ic50 of 3 nmol/l and showed minimal cross-reactivity against a panel of kinases at 1 mmol/l. cct241533 did not potentiate the cytotoxicity of a selection of genotoxic agents in several cell lines [1]. moreover, as the most potent chk2 inhibitor identified in the series, cct241533 showed potent selectivity (63-fold) over chk1 and low herg inhibition [2].
[1] anderson ve, walton mi, eve pd, boxall kj, antoni l, caldwell jj, aherne w, pearl lh, oliver aw, collins i, garrett md. cct241533 is a potent and selective inhibitor of chk2 that potentiates the cytotoxicity of parp inhibitors. cancer res. 2011;71(2):463-72.
[2] caldwell jj, welsh ej, matijssen c, anderson ve, antoni l, boxall k, urban f, hayes a, raynaud fi, rigoreau lj, raynham t, aherne gw, pearl lh, oliver aw, garrett md, collins i. structure-based design of potent and selective 2-(quinazolin-2-yl)phenol inhibitors of checkpoint kinase 2. j med chem. 2011;54(2):580-90.
