MS1943

MS1943 is a proteolysis-targeting chimera (PROTAC) that contains the selective enhancer of zeste homolog 2 (EZH2) inhibitor C24 linked to an adamantyl group. It inhibits EZH2 (IC50 = 120 nM) and is selective for EZH2 over EZH1, as well as a panel of 45 kinases at 10 µM. MS1943 (4 µM) induces EZH2 degradation and reduces histone H3 lysine 27 trimethylation (H3K27me3), as well as induces activation of the unfolded protein response pathway in MDA-MB-468 triple-negative breast cancer (TNBC) cells. It inhibits the growth of MDA-MB-468 cells in vitro (GI50 = 2.2 µM) and reduces tumor volume in an MDA-MB-468 mouse xenograft model when administered at a dose of 50 mg/kg.Formal Name: N-[(1,2-dihydro-4,6-dimethyl-2-oxo-3-pyridinyl)methyl]-1-(1-methylethyl)-6-[6-[4-[2-[(2-tricyclo[3.3.1.13,7]dec-1-ylacetyl)amino]ethyl]-1-piperazinyl]-3-pyridinyl]-1H-indazole-4-carboxamide. CAS Number: 2225938-17-8. Molecular Formula: C42H54N8O3. Formula Weight: 718.9. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMF: 2 mg/ml, DMSO: 2 mg/ml, Ethanol: 2 mg/ml, PBS (pH 7.2): insol. lambdamax: 228, 284, 317 nm. SMILES: CC(C)N1N=CC2=C(C=C(C3=CC=C(N4CCN(CC4)CCNC(CC56CC7CC(C6)CC(C5)C7)=O)N=C3)C=C21)C(NCC8=C(C)C=C(C)NC8=O)=O. InChi Code: InChI=1S/C42H54N8O3/c1-26(2)50-37-18-33(17-34(36(37)25-46-50)40(52)45-24-35-27(3)13-28(4)47-41(35)53)32-5-6-38(44-23-32)49-11-9-48(10-12-49)8-7-43-39(51)22-42-19-29-14-30(20-42)16-31(15-29)21-42/h5-6,13,17-18,23,25-26,29-31H,7-12,14-16,19-22,24H2,1-4H3,(H,43,51)(H,45,52)(H,47,53). InChi Key: WQIQJFXBAJJKNT-UHFFFAOYSA-N.