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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 μM 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 , Black: linker ; Pink: PRC1 ligand ).