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MS8847
- Development stage
- Preclinical
- Lead developer
- Icahn School of Medicine
- Modality
- PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules
01
Overview
MS8847 is a highly potent, von Hippel-Lindau (VHL)-recruiting proteolysis-targeting chimera (PROTAC) degrader of Enhancer of Zeste Homolog 2 (EZH2). Developed by the Icahn School of Medicine at Mount Sinai, MS8847 induces EZH2 degradation via the ubiquitin-proteasome system in a concentration-, time-, and ubiquitin-proteasome system (UPS)-dependent manner. It targets both the canonical methyltransferase activity and non-canonical, non-enzymatic oncogenic functions of EZH2. MS8847 has demonstrated superior EZH2 degradation and anti-proliferative activity compared to earlier EZH2 degraders in MLL-rearranged (MLL-r) acute myeloid leukemia (AML) and triple-negative breast cancer (TNBC) models, and possesses a favorable pharmacokinetic profile suitable for in vivo studies.
02
Targets
EZH2 (Histone-lysine N-methyltransferase EZH2)VHL (Von Hippel–Lindau tumor suppressor protein)
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