2. Academic Validation
  3. Discovery and Optimization of Tetramethylpiperidinyl Benzamides as Inhibitors of EZH2

Discovery and Optimization of Tetramethylpiperidinyl Benzamides as Inhibitors of EZH2

  • ACS Med Chem Lett. 2014 Jan 14;5(4):378-83. doi: 10.1021/ml400494b.
Christopher G Nasveschuk 1,  Alexandre Gagnon 1,  Shivani Garapaty-Rao 1,  Srividya Balasubramanian 1,  Robert Campbell 1,  Christina Lee 1,  Feng Zhao 1,  Louise Bergeron 1,  Richard Cummings 1,  Patrick Trojer 1,  James E Audia 1,  Brian K Albrecht 1,  Jean-Christophe P Harmange 1
Affiliations

Affiliation

  • 1 Constellation Pharmaceuticals , 215 1st Street, Suite 200, Cambridge, Massachusetts 02142, United States.
PMID: 24900844 DOI: 10.1021/ml400494b
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.

Keywords

EZH2; KARPAS-422; PRC2; diphenylether; methyltransferase; tetramethylpiperidine.

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