EPZ-6438 --- EZH2 Methyltransferase Inhibitor

Overview
Catalog #	bs-60122c-2-mg-solid
Product Name	EPZ-6438 --- EZH2 Methyltransferase Inhibitor
Specifications
Storage Buffer	Powder
Storage Condition	Store in dry, dark place at -20C for 1 year.
Target
Product Information	Molecular Weight: 572.74 Formula: C34 H44 N4 O4 CAS Number: 1403254-99-8 InChi Key: NSQSAUGJQHDYNO-UHFFFAOYSA-N InChi: InChI=1S/C34H44N4O4/c1-5-38(29-10-14-41-15-11-29)32-20-28(27-8-6-26(7-9-27)22-37-12-16-42-17-13-37)19-30(25(32)4)33(39)35-21-31-23(2)18-24(3)36-34(31)40/h6-9,18-20,29H,5,10-17,21-22H2,1-4H3,(H,35,39)(H,36,40) Smiles: CCN(C1CCOCC1)C1=CC(=CC(C(=O)NCC2C(=O)NC(C)=CC=2C)=C1C)C1=CC=C(CN2CCOCC2)C=C1 Purity: 98.0 Solubility: DMSO up to 100 mM Appearance: Solid Power. Shelf Life: 1.0 years
Description	EPZ-6438 (E7438) is a potent and selective small molecule inhibitor of histone methyltransferase EZH2. It inhibited the activity of human PRC2-containing wild-type EZH2 with an inhibition constant (Ki) value of 2.5 ± 0.5 nM, and similar potency was observed for EZH2 proteins bearing all known lymphoma change-of-function mutations. EPZ-6438 inhibits EZH2 in a manner competitive with the substrate S-adenosylmethionine (SAM). EPZ-6438 displayed a 35-fold selectivity versus EZH1 and >4, 500-fold selectivity relative to 14 other HMTs (encompassing both lysine and arginine HMTs) tested. It specifically inhibits cellular H3K27 methylation leading to selective apoptotic killing of SMARCB1 mutant MRT Cells. It also induced genes of neuronal differentiation and cell cycle inhibition while suppressing expression of Hedgehog pathway genes, MYC and EZH2. Moreover EPZ-6438 leads to complete and sustained regression of SMARCB1 mutant MRT xenografts, and sevral EZH2 mutant xenografts including WSU-DLCL2 (Y614F), Pfeiffer (Y677G), KARPAS-422 (Y641N) etc. Epizyme has initiated a Phase 1/2 clinical trials targeting the treatment of non-Hodgkin lymphoma.