An orally bioavailable EZH2 inhibitor
The lysine methyltransferase EZH2 (KMT6), part of polycomb repressive complex 2, catalyzes trimethylation of lysine 27 on histone H3 and is involved in proliferation and aggressive cell growth associated with neoplastic cells.1 EPZ011989 is an orally bioavailable EZH2 inhibitor with Ki values that are less than 3 nM for wild type and Tyr646 mutated EZH2.2 It displays 15-fold selectivity for EZH2 over EZH1 and is without effect against an array of other lysine methyltransferases.2 EPZ011989 demonstrates significant tumor growth inhibition in a mouse xenograft model of human B cell lymphoma.2
1.Simon, J.A., and Lange, C.A.Roles of the EZH2 histone methyltransferase in cancer epigeneticsMutat. Res.647(1-2)21-29(2008) 2.Campbell, J.E., Kuntz, K.W., Knutson, S.K., et al.EPZ011989, a potent, orally-available EZH2 inhibitor with robust in vivo activityACS Med. Chem. Lett.6(5)491-495(2015)
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