BLU-222 is an orally active and highly selective CDK2 inhibitor. BLU-222 disrupts Rb signaling and causes G1 arrest and apoptosis in CCNE1-amplified endometrial cancer cells.
BLU-222 (25-250 nM; 0-288 h) exhibits antiproliferative activity against KLE and HEC-1-B cell lines[2].
BLU-222 (60 mg/kg; twice daily) shows significant anti-tumor activity in both endometrial cancer PDX models[3].
References:
[1]. Talbot T, et al. Amplified therapeutic targets in high-grade serous ovarian carcinoma - a review of the literature with quantitative appraisal. Cancer Gene Ther. 2023 Jul;30(7):955-963.
[2]. House N, et al. BLU-222, a potent and highly selective CDK2 inhibitor, demonstrated antitumor activity as monotherapy and as combination treatment in CCNE1-aberrant endometrial cancer models[J]. Cancer Research, 2024, 84(6_Supplement): 1959-1959. [3]. Luo L, et al. Abstract PO1-18-05: Combination treatment with CDK2 inhibitor (BLU-222) and either palbociclib or ribociclib is synergistic in pre-clinical models of CDK4/6 inhibitor-resistant breast cancer[J]. Cancer Research, 2024, 84(9_Supplement): PO1-18-05-PO1-18-05.