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Updated: Apr 12, 2026

Identifying Inhibitors of the HBx-DDB1 Interaction Using a Split Luciferase Assay System
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EPZ011989, A Potent, Orally-Available EZH2 Inhibitor with Robust in Vivo Activity

John E Campbell1, Kevin W Kuntz1, Sarah K Knutson1

  • 1Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02139, United States.

ACS Medicinal Chemistry Letters
|May 26, 2015
PubMed

Insights

Researchers developed EPZ011989, a new drug targeting Enhancer of Zeste Homolog 2 (EZH2). This potent compound shows promise for treating B cell lymphomas and aids further study of EZH2 in cancer biology.

Area of Science:

  • Biochemistry
  • Oncology
  • Pharmacology

Background:

  • Enhancer of Zeste Homolog 2 (EZH2) is a protein methyltransferase with therapeutic potential for B cell lymphomas and other cancers.
  • The lack of in vivo-active tool compounds has limited the exploration of EZH2-associated pathobiology.

Purpose of the Study:

  • To discover and characterize a novel, in vivo-active small molecule inhibitor of EZH2.
  • To provide a tool compound for further research into EZH2's role in cancer.

Main Methods:

  • Discovery and characterization of EPZ011989, an orally bioavailable EZH2 inhibitor.
  • Pharmacokinetic profiling and in vivo efficacy studies in a mouse xenograft model.

Main Results:

  • EPZ011989 was identified as a potent and selective inhibitor of EZH2.
  • The compound exhibited favorable pharmacokinetic properties and oral bioavailability.
  • Significant tumor growth inhibition was observed in a mouse xenograft model of human B cell lymphoma.

Conclusions:

  • EPZ011989 is a potent, selective, and orally bioavailable EZH2 inhibitor with demonstrated in vivo activity.
  • This compound serves as a valuable tool for advancing the understanding of EZH2 in cancer biology and therapeutic development.
Keywords:
B cell lymphomaEZH2KARPAS-422MethyltransferasePRC2in vivo chemical probexenograft

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