| Literature DB >> 26189078 |
Victor S Gehling1, Rishi G Vaswani2, Christopher G Nasveschuk2, Martin Duplessis2, Priyadarshini Iyer2, Srividya Balasubramanian2, Feng Zhao2, Andrew C Good2, Robert Campbell2, Christina Lee2, Les A Dakin2, Andrew S Cook2, Alexandre Gagnon2, Jean-Christophe Harmange2, James E Audia2, Richard T Cummings2, Emmanuel Normant2, Patrick Trojer2, Brian K Albrecht2.
Abstract
The discovery and optimization of a series of small molecule EZH2 inhibitors is described. Starting from dimethylpyridone HTS hit (2), a series of indole-based EZH2 inhibitors were identified. Biochemical potency and microsomal stability were optimized during these studies and afforded compound 22. This compound demonstrates nanomolar levels of biochemical potency (IC50=0.002 μM), cellular potency (EC50=0.080 μM), and afforded tumor regression when dosed (200 mpk SC BID) in an EZH2 dependent tumor xenograft model.Entities:
Keywords: EZH2; Epigenetics; Histone methyltransferase; PRC2; Pyridone
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Year: 2015 PMID： 26189078 DOI： 10.1016/j.bmcl.2015.06.056
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823