MRT-9643

MRT-9643 is a potent, selective, and orally active molecular glue degrader that targets cyclin-dependent kinase 2 (CDK2). It induces deep degradation of CDK2, resulting in inhibition of CDK2-dependent cancer cell growth. Unlike traditional catalytic-site inhibitors, MRT-9643 engages CDK2 through a novel binding mode that does not utilize the catalytic site, enabling superior selectivity over other conserved cyclin-dependent kinases and kinases. In preclinical models—particularly for hormone receptor-positive (HR-positive), HER2-negative breast cancer—MRT-9643 demonstrated robust downstream pathway suppression and deep tumor regression when combined with standard-of-care therapies such as CDK4/6 inhibitors or endocrine therapy. The drug is being developed by Monte Rosa Therapeutics and remains in the preclinical stage[1][4][5][6].