BLU-020

BLU-020 is an orally bioavailable, potent, and selective small molecule degrader of cyclin-dependent kinase 2 (CDK2) developed by Blueprint Medicines. It is designed to treat cancers characterized by *CCNE1* aberrations, such as CCNE1-amplified ovarian cancer. By selectively inducing the degradation of CDK2, BLU-020 aims to inhibit the Cyclin E1/CDK2 complex, leading to pRb inhibition, G1 cell cycle arrest, and suppression of E2F-targeted genes. This targeted protein degradation approach is intended to provide superior selectivity over other CDK family members, potentially reducing off-target toxicities commonly associated with pan-CDK inhibitors. Preclinical studies have demonstrated robust anti-tumor activity in models of CCNE1-amplified cancers, both as a monotherapy and in combination with other agents like ribociclib.