EPZ011989, A Potent, Orally-Available EZH2 Inhibitor with Robust in Vivo Activity
- PMID: 26005520
- PMCID: PMC4434464
- DOI: 10.1021/acsmedchemlett.5b00037
EPZ011989, A Potent, Orally-Available EZH2 Inhibitor with Robust in Vivo Activity
Abstract
Inhibitors of the protein methyltransferase Enhancer of Zeste Homolog 2 (EZH2) may have significant therapeutic potential for the treatment of B cell lymphomas and other cancer indications. The ability of the scientific community to explore fully the spectrum of EZH2-associated pathobiology has been hampered by the lack of in vivo-active tool compounds for this enzyme. Here we report the discovery and characterization of EPZ011989, a potent, selective, orally bioavailable inhibitor of EZH2 with useful pharmacokinetic properties. EPZ011989 demonstrates significant tumor growth inhibition in a mouse xenograft model of human B cell lymphoma. Hence, this compound represents a powerful tool for the expanded exploration of EZH2 activity in biology.
Keywords: B cell lymphoma; EZH2; KARPAS-422; Methyltransferase; PRC2; in vivo chemical probe; xenograft.
Conflict of interest statement
The authors declare the following competing financial interest(s): J.E.C., K.W.K., S.K.K., N.M.W., H.K., T.J.W., A.R., C.R.K., N.R., M.P.S., N.J.W., J.J.S., R.C., M.P.M., and R.A.C. have ownership interest (including patents) in Epizyme.
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