MRT-50969

MRT-50969 is a preclinical, orally bioavailable molecular glue degrader developed by Monte Rosa Therapeutics. It selectively targets and degrades cyclin E1 (CCNE1), a non-enzymatic driver oncogene frequently amplified or overexpressed in various solid tumors, including breast, gastric, ovarian, and endometrial cancers. By inducing proteasomal degradation of cyclin E1 via cereblon-based molecular glue mechanisms, MRT-50969 suppresses downstream cell cycle pathways—specifically downregulating RB phosphorylation and E2F-driven gene expression—leading to G1-S cell cycle arrest and senescence in CCNE1-amplified cancer cells while sparing non-amplified cells. This selectivity distinguishes it from CDK2 inhibitors and may reduce toxicity associated with broader cyclin/CDK inhibition. Preclinical studies have shown robust tumor growth suppression and regression in CCNE1-amplified breast and gastric cancer models[2][4][5][6][8].