MS177

SKU: orb3054181

Description

MS177 is an effective and fast-acting EZH2 degrader. MS177 is a PROTAC that consists of a CRBN ligand, linker, and a potent enzymatic EZH2 inhibitor C24 (C24 IC50): 12 nM).

Key Properties

• CAS Number: 2225938-86-1
• MW: 914.02
• Purity: >98% (HPLC)
• Formula: C₄₈H₅₅N₁₁O₈
• Solubility: DMSO : 125 mg/mL (136.76 mM; ultraphonic; )

Bioactivity

• In Vivo:
  MS177 (100 mg/kg, i.p. , BID for 6 days) represses tumor growth in PDX Animal model of MLL-r AML, and in subcutaneously xenografted MLL-r leukaemia models. MS177 (50 mg/kg, i.p.) achieves intraplasma concentrations about 1 μM in male Swiss Albino mice. MS177 (100 mg/kg, i.p. , BID for 6 days per week; and 200 mg/kg, i.p. BID 3 days per week) is well tolerated and lacks apparent toxicity in mice. Animal model: PDX Animal model of MLL-r AML. Dosage: 100 mg/kg. Administration: Intraperitoneal injection (i.p.), BID for 6 days. Result: Inhibited tumor growth and prolonged survival.
• In Vitro:
  MS177 inhibits the enzymatic activities of EZH2-PRC2 (IC50: 7 nM). MS177 (5 μM, 24 h) decreases H3K27me3 and increases H3K27activity in HeLa cells. MS177 (0.1-5 μM, 16 h) effectively degrades cellular EZH2-PRC2 and suppresses global H3K27me3 in EOL-1 cells. MS177 (0.1-5 μM, 16 h) induces Myc degradation in EOL-1 and MV4 cells. MS177 (4 days) shows antiproliferation effects in a panel of MLL-r leukaemia cells and samples from patients with AML, with IC50s below 2 μM. MS177 (0.5-2.5 μM, 24 h) decreases colony-forming capabilities in MV4; 11 cells. MS177 (0.5-2.5 μM, 24 h) slows cell cycle progression and induces MOLM-13 cell apoptosis. Cell Viability Assay Cell line: AML cell line: MV4; 11, MOML-13, RS4; 11, KOPN-8 THP-1, EOL-1 (MLL-r cells) Control cell line: K562 (CML cells) Patient sample: AML cells. Concentration: 0-100 μM approximately. Incubation time: 4 days. Result: Inhibited cell proliferation with IC50s of 0.1-0.57 μM for MLL-r cells, 0.09-1.35 μM for Patient sample, >100 μM for K562 cell. Western blot analysis. Cell line: EOL-1 cell. Concentration: 0.1, 0.5, 1, 2.5, 5 μM Incubation time: 16 h. Result: Depleted EZH2, EED and SUZ12 in a concentration-dependent manner and suppressed global H3K27me3.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only