CDD-1274 is an inhibitor of the ERα (estrogen receptor α) variant. It facilitates the proteasomal degradation of ERα variants in breast cancer cell lines, leading to the degradation of Y537SERα. CDD-1274 effectively blocks both ligand-dependent and ligand-independent ER signaling pathways in endocrine-resistant breast cancer cells. It is used in breast cancer research.

CDD-1274 at a concentration of 10 μM effectively inhibits the recruitment of SRC3 coactivator peptide to Y537S and D538G mutated ERα LBD. It reduces protein levels of wild-type and Y537S ERα in T47D parental and Y537S mutant cells, along with decreased expression of cyclin D1, survivin, and progesterone receptor (PR). Treatment with 10 μM CDD-1274 for 24 hours also decreases ERα protein levels in MCF-7 parental cells and MCF-7 Y537S and D538G mutants, reduces markers of cell proliferation (cyclin D1, survivin, E2F1), and downregulates ER target genes (TFF1, GREB1, PR), while increasing the expression of the apoptosis marker c-PARP. In palbociclib-resistant MCF-7 WT and Y537S cells, CDD-1274 degrades both WT and Y537S ERα, inhibiting expression of cyclin D1, survivin, and TFF1. In ER-positive cells like T47D and MCF-7, CDD-1274 reduces levels of ERα and proliferation markers. Conversely, in ER-negative cells (MCF-10A, HCC1954, MDA-MB-231, and VCaP), it acts as a pure antagonist. CDD-1274 (10 μM, 24 hours) induces sustained degradation of ERα in T47D parental and T47D Y537S mutant cells.