1844849-10-0

PF-06821497 is an enhancer of zeste homolog 2 (EZH2) inhibitor (Ki = <0.1 nM for EZH2Y641N).1 It is selective for EZH2 over a panel of 14 methyltransferases, 40 kinases, and 79 additional targets at 10 µM but does bind to EZH1 (Ki = 70 nM). PF-06821497 reduces trimethylation of lysine 27 on histone H3 (H3K27Me3) in, and the proliferation of, Karpas-422 non-Hodgkin lymphoma cells, which endogenously express EZH2Y641N (IC50s = 4 and 6 nM, respectively). In vivo, PF-06821497 (100 mg/kg, s.c.) induces tumor regression in a Karpas-422 mouse xenograft model.WARNING This product is not for human or veterinary use.

[1] PEI-PEI KUNG*. Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors Using Ligand and Property-Based Design Strategies: Identification of Development Candidate (R)-5,8-Dichloro-7-(methoxy(oxetan-3-yl)methyl)-2-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3,4-dihydroisoquinolin-1(2H)-one (PF-06821497)[J]. Journal of Medicinal Chemistry, 2017, 61 3: 650-665. DOI: 10.1021/acs.jmedchem.7b01375