INCB127443 is a potent, selective and orally bioavailable CDK2 inhibitor with IC50 of 0.99 nM (CDK2/cyclin E1), 316-fold selective over CDK1.
INCB127443 has 12- and 86-fold selectivity over CDK4 and CDK6.
INCB127443 potently inhibits retinoblastoma protein (Rb) S780 phosphorylation with IC50 of 21 nM in CCNE1-high COV318 cells.
INCB127443 inhibits Rb S780 phosphorylation with IC50 of 310 nM in whole-blood assays.
INCB127443 demonstrates robust selectivity over CDK5/p35 (245-fold).
INCB127443 displays strong activity in the CDK2-dependent COV318 cell line (IC50=21 nM) and maintains selectivity over CDK4 and CDK6, with IC50 values of 445 and 448 nM in CDK4-dependent JeKo-1 and CAL-51 cells (21-fold) and 416 nM in the CDK6-dependent MV-4-11 cell line (20-fold).
INCB127443 induced potent S-phase suppression in CCNE1-high COV318 (IC50=6.7 nM) and OVCAR-3 (IC50=27 nM) cells.
INCB127443 demonstrates robust pharmacodynamic inhibition of Rb phosphorylation and significant antitumor activity in the OVCAR-3 xenograft model.