CPI-169

CPI-169 (R) is a novel and potent EZH2 inhibitor.

Product information

CAS Number: 1802175-07-0

Molecular Weight: 528.66

Formula: C27H36N4O5S

Synonym:

CPI169 R-enantiomer

CPI 169 R-enantiomer

Chemical Name: 1-[(1R)-1-[1-(ethanesulfonyl)piperidin-4-yl]ethyl]-N-[(4-methoxy-6-methyl-2-oxo-1, 2-dihydropyridin-3-yl)methyl]-2-methyl-1H-indole-3-carboxamide

Smiles: C[C@H](C1CCN(CC1)S(=O)(=O)CC)N1C2=CC=CC=C2C(C(=O)NCC2=C(C=C(C)NC2=O)OC)=C1C

InChiKey: LHGUZCKPFXXVPV-GOSISDBHSA-N

InChi: InChI=1S/C27H36N4O5S/c1-6-37(34,35)30-13-11-20(12-14-30)18(3)31-19(4)25(21-9-7-8-10-23(21)31)27(33)28-16-22-24(36-5)15-17(2)29-26(22)32/h7-10,15,18,20H,6,11-14,16H2,1-5H3,(H,28,33)(H,29,32)/t18-/m1/s1

Technical Data

Appearance: Solid Power

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

Solubility: DMSO : ≥ 100 mg/mL (189.16 mM)

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

How to use

In Vitro:

CPI-169 (CPI 169 R-enantiomer) inhibits the catalytic activity of PRC2 with an IC50 of < 1nM, decreases cellular levels of H3K27me3 with an EC50 of 70 nM, and triggers cell cycle arrest and apoptosis in a variety of cell lines. In KARPAS-422 cells, CPI-169 shows a dose-dependent inhibitory effect on cell viability, and produces synergy anti-proliferative activity when used in combination with ABT-199. In 16 out of 25 NHL cell lines, CPI-169 also suppresses cell growth with GI50 of <5 μM.

In Vivo:

CPI-169 (CPI 169 R-enantiomer) (200 mpk, s.c. BID) is well tolerated in mice with no observed toxic effect or body weight loss. CPI-169 treatment leads to tumor growth inhibition (TGI) of an EZH2 mutant KARPAS-422 DLBCL xenograft. CPI-169 (100 mpk, BID) with a single dose of CHOP leads tumors to rapidly regress and become unpalpable. In mice bearing KARPAS-422 xenografts, CPI-169 (200 mg/kg, s.c.) effectively suppresses H3K27me3 levels and results in lymphoma tumor regression without affecting body weight or causing any overt adverse effects.

References:

1. Vidya Balasubramanian, et al. CPI-169, a novel and potent EZH2 inhibitor, synergizes with CHOP in vivoand achieves complete regression in lymphoma xenograft models. Cancer Res October 1, 2014 74; 1697
2. Bradley WD, et al. EZH2 inhibitor efficacy in non-Hodgkin's lymphoma does not require suppression of H3K27 monomethylation. Chem Biol. 2014 Nov 20;21(11):1463-75

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