2. Academic Validation
  3. Novel HDAC6 isoform selective chiral small molecule histone deacetylase inhibitors

Novel HDAC6 isoform selective chiral small molecule histone deacetylase inhibitors

  • Bioorg Med Chem Lett. 2009 Feb 1;19(3):688-92. doi: 10.1016/j.bmcl.2008.12.045.
David V Smil 1,  Sukhdev Manku,  Yves A Chantigny,  Silvana Leit,  Amal Wahhab,  Theresa P Yan,  Marielle Fournel,  Christiane Maroun,  Zuomei Li,  Anne-Marie Lemieux,  Alina Nicolescu,  Jubrail Rahil,  Sylvain Lefebvre,  Anthony Panetta,  Jeffrey M Besterman,  Robert Déziel
Affiliations

Affiliation

  • 1 MethylGene Inc, Department of Medicinal Chemistry, 7220 Frederick-Banting, Montréal, Que., Canada H4S 2A1. [email protected]
PMID: 19111466 DOI: 10.1016/j.bmcl.2008.12.045
Abstract

In an effort to identify HDAC isoform selective inhibitors, we designed and synthesized novel, chiral 3,4-dihydroquinoxalin-2(1H)-one and piperazine-2,5-dione aryl hydroxamates showing selectivity (up to 40-fold) for human HDAC6 over Other class I/IIa HDACs. The observed selectivity and potency (IC(50) values 10-200 nM against HDAC6) is markedly dependent on the absolute configuration of the chiral moiety, and suggests new possibilities for use of chiral compounds in selective HDAC isoform inhibition.

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