Phenylalanine-containing hydroxamic acids as selective inhibitors of class IIb histone deacetylases (HDACs)

ISSN
0968-0896
Date Issued
2008
Author(s)
Schaefer, Stefan
Saunders, Laura
Eliseeva, Elena
Velena, Alfredo
Jung, Mira
Strasser, Anja
Schlimme, Sonja
Sippl, Wolfgang
Verdin, Eric
Jung, Manfred
DOI
10.1016/j.bmc.2007.10.092
Abstract
We synthesized biarylalanine-containing hydroxamic acids and tested them on immunoprecipitated HDAC1 and HDAC6 and show a subtype selectivity for HDAC6 that was confirmed in cells by Western blot (tubulin vs histones). We obtained an X-ray structure with a HDAC6-selective inhibitor with the bacterial deacetylase HDAH. Docking studies were carried out using HDAC1 and HDAC6 protein models. Antiproliferative activity was shown on cancer cells for selected compounds. (c) 2007 Elsevier Ltd. All rights reserved.