MS8815

**MS8815** is a bifunctional PROTAC degrader designed to target **enhancer of zeste homolog 2 (EZH2)**, a histone methyltransferase overexpressed in triple-negative breast cancer (TNBC) and associated with poor prognosis. It recruits the **von Hippel-Lindau (VHL)** E3 ubiquitin ligase using the VHL-1 ligand (VH032) linked to the EZH2 inhibitor **tazemetostat (EPZ-6438)**, inducing concentration-, time-, and proteasome-dependent degradation of EZH2 with DC50 of 140 nM in TNBC cells, alongside degradation of PRC2 components EED and SUZ12, and reduction of H3K27me3. MS8815 demonstrates nanomolar potency, high selectivity over other methyltransferases (except biochemical inhibition of EZH1 without degradation), superior anti-proliferative effects (GI50 ~1-3 μM) compared to inhibitors like tazemetostat or YM281 in multiple TNBC cell lines and primary patient TNBC cells, good mouse bioavailability via IP (Cmax 3.7 μM at 50 mg/kg), and no off-target degradation.[1][2][3][5][8]

Other names

MS-8815MS8815MS 8815