MS147

Description

MS147 is a VHL-based PROTAC degrader of PRC1 Polycomb Repressive Complex 1 . The dissociation constants Kd of MS147 for EED Embryonic Ectoderm Development and VHL Von Hippel-Lindau are 3.0 ?M and 450 nM, respectively. MS147 specifically binds to the EED protein through its EED-binding moiety; EED is a core component of PRC2 Polycomb Repressive Complex 2 and interacts with the core components of PRC1, BMI1 B-lymphoma Mo-MLV insertion region 1 homolog and RING1B Ring Finger Protein 1B . By this binding, MS147 is able to recruit BMI1 and RING1B near to VHL. Through the degradation of BMI1 and RING1B, MS147 reduces the level of H2AK119ub histone H2A lysine 119 ubiquitination , affecting the proliferation of cancer cells. Blue: VHL ligand HY-125845 , Black: linker ; Pink: PRC1 ligand HY-158771 .