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Discovery and Optimization of Tetramethylpiperidinyl Benzamides as Inhibitors of EZH2.

ABSTRACT: The identification and development of a novel series of small molecule Enhancer of Zeste Homologue 2 (EZH2) inhibitors is described. A concise and modular synthesis enabled the rapid development of structure-activity relationships, which led to the identification of 44 as a potent, SAM-competitive inhibitor of EZH2 that dose-dependently decreased global H3K27me3 in KARPAS-422 lymphoma cells.

SUBMITTER: Nasveschuk CG

PROVIDER: S-EPMC4027731 | biostudies-other | 2014 Apr

REPOSITORIES: biostudies-other

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Discovery and Optimization of Tetramethylpiperidinyl Benzamides as Inhibitors of EZH2.

Nasveschuk Christopher G CG Gagnon Alexandre A Garapaty-Rao Shivani S Balasubramanian Srividya S Campbell Robert R Lee Christina C Zhao Feng F Bergeron Louise L Cummings Richard R Trojer Patrick P Audia James E JE Albrecht Brian K BK Harmange Jean-Christophe P JC

ACS medicinal chemistry letters 20140114 4

The identification and development of a novel series of small molecule Enhancer of Zeste Homologue 2 (EZH2) inhibitors is described. A concise and modular synthesis enabled the rapid development of structure-activity relationships, which led to the identification of 44 as a potent, SAM-competitive inhibitor of EZH2 that dose-dependently decreased global H3K27me3 in KARPAS-422 lymphoma cells. ...[more]

PMID: 24900844

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