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Title: Human HDAC isoform selectivity achieved via exploitation of the acetate release channel with structurally unique small molecule inhibitors

Herein we report the discovery of a family of novel yet simple, amino-acid derived class I HDAC inhibitors that demonstrate isoform selectivity via access to the internal acetate release channel. Isoform selectivity criteria is discussed on the basis of X-ray crystallography and molecular modeling of these novel inhibitors bound to HDAC8, potentially revealing insights into the mechanism of enzymatic function through novel structural features revealed at the atomic level.
Authors:
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;  [1]
  1. (Novartis)
Publication Date:
OSTI Identifier:
1025628
Resource Type:
Journal Article
Resource Relation:
Journal Name: Bioorg. Med. Chem. Lett.; Journal Volume: 19; Journal Issue: (15) ; 08, 2011
Research Org:
Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
Sponsoring Org:
INDUSTRY
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; ACETATES; CRYSTALLOGRAPHY; HISTONES; HYPOTHESIS; SIMULATION