CDD-1274

CDD-1274 is a novel, small-molecule selective estrogen receptor degrader (SERD) and variant inhibitor discovered using a DNA-encoded chemical library (DECL) platform. It is designed to target both wild-type (WT) and mutant forms of estrogen receptor alpha (ERα), specifically the Y537S and D538G mutations in the ligand-binding domain (LBD) that drive endocrine resistance in metastatic ER-positive breast cancer. CDD-1274 acts by blocking the recruitment of the coactivator SRC3 to the ERα LBD, thereby inhibiting both ligand-dependent and ligand-independent ER signaling. Furthermore, it induces proteasome-dependent degradation of both wild-type and mutant ERα variants, leading to decreased expression of downstream proliferation markers (such as cyclin D1, survivin, and progesterone receptor) and triggering apoptosis in ER-positive breast cancer cells.