Cirtociclib (BLU-222) is a potent, highly selective, ATP-competitive CDK2 inhibitor with IC50 of 2.6 nM (CDK2/cyclinE1) with strong selectivity (>200-fold) over CDK family members (1/4/6/7/9).
BLU-222 has excellent kinome selectivity with an S(10) of 0.045, measured by KINOMEscan at 3 µM.
BLU-222 displays nanomolar cellular potency on phosphorylated Rb (pRb) T821/826 with strong selectivity over pLamin S22, a measure of CDK1 activity in CDK2-dependent cell line OVCAR-3.
BLU-222 displays nanomolar cellular potency on phosphorylated Rb (pRb) T821/826 with strong selectivity over pLamin S22, a measure of CDK1 activity. BLU-222 potently and dose-dependently inhibited proliferation in CCNE1amplified ovarian/endometrial cancer cell lines, while sparing CCNE1-normal (diploid, mRNA not overexpressed) cell lines.
BLU-222 disrupts Rb signaling in CCNE1-amplified cells to arrest cell cycle progression. BLU-222 demonstrated robust activity in combination with carboplatin or paclitaxel in CCNE1-aberrant models, rendering chemotherapy-resistant tumors strongly sensitive to the combination.