EPZ011989

EPZ011989 is a potent, selective orally bioavailable EZH2 inhibitor with Ki < 3 nM for EZH2 wt and EZH2 Y646; 15-fold selectivity over EZH1 and >3000-fold selectivity over other HMTase.IC50 value: < 3 nM ( Ki for wt EZH2, EZH2 Y646)Target: EZH2 inhibitorIn vitro: EPZ011989 is also a specific EZH2 inhibitor with a >15-fold selectivity over EZH1 and >3000-fold selectivity relative to the Ki of 20 other histone methyltransferases (HMTs) tested. EPZ011989 also exhibits metabolic stability. Furthermore, EPZ011989 reduces cellular H3K27 methylation in the Y641F, mutant-bearing human lymphoma cell line, WSU-DLCL2, with an IC50 below 100 nM. This functional response translates to activity in a long-term proliferation assay where EPZ011989 demonstrates an average lowest cytotoxic concentration (LCC) in WSU-DLCL2 cells of 208 nM. In vivo: The LCC parameter, when corrected for plasma protein-binding, predicts an efficacious plasma level in mouse for EPZ011989 of 158 ng/mL. The pharmacokinetics in SCID mice following oral administration of 125, 250, 500, and 1000 mg/kg indicated that the 1000 mg/kg dose provided coverage over the LCC for 24 h, while the 250 and 500 mg/kg doses provided coverage over this value for approximately 8 h. EPZ011989 demonstrates significant tumor growth inhibition in a mouse xenograft model of human B cell lymphoma.

Product information

CAS Number: 1598383-40-4

Molecular Weight: 605.81

Formula: C35H51N5O4

Chemical Name: N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-3-{ethyl[(1r,4r)-4-[(2-methoxyethyl)(methyl)amino]cyclohexyl]amino}-2-methyl-5-[3-(morpholin-4-yl)prop-1-yn-1-yl]benzamide

Smiles: CN(CCOC)[C@@H]1CC[C@H](CC1)N(CC)C1C=C(C=C(C(=O)NCC2C(=O)NC(C)=CC=2C)C=1C)C#CCN1CCOCC1

InChiKey: XQFINGFCBFHOPE-WXUXXXNLSA-N

InChi: InChI=1S/C35H51N5O4/c1-7-40(30-12-10-29(11-13-30)38(5)15-18-43-6)33-23-28(9-8-14-39-16-19-44-20-17-39)22-31(27(33)4)34(41)36-24-32-25(2)21-26(3)37-35(32)42/h21-23,29-30H,7,10-20,24H2,1-6H3,(H,36,41)(H,37,42)/t29-,30-

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 100 mg/mL (165.07 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

Products are for research use only. Not for human use.