The structural requirements of histone deacetylase inhibitors: Suberoylanilide hydroxamic acid analogs modified at the C3 position display isoform selectivity

被引：25
作者：
Choi, Sun Ea [1 ]
Weerasinghe, Sujith V. W. [1 ]
Pflum, Mary Kay H. [1 ]
机构：
[1] Wayne State Univ, Dept Chem, Detroit, MI 48202 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 20期
基金：
美国国家卫生研究院;
关键词：
Histone deaceylases; HDAC inhibitors; Vorinostat; Isoform selectivity; HDAC INHIBITORS; CANCER; DESIGN; POTENT; PROTEASOME; EXPRESSION; THERAPY; CELLS;
D O I：
10.1016/j.bmcl.2011.08.027
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The FDA-approved drug suberoylanilide hydroxamic acid (SAHA, Vorinostat) was modified to improve its selectivity for a single histone deaetylase (HDAC) isoform. We show that attaching an ethyl group at the C3 position transforms SAHA from nonselective to an HDAC6-selective inhibitor. Theses results indicate that small structural changes in SAHA can significantly influence selectivity, which will lead future anticancer design efforts targeting HDAC proteins. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码：6139 / 6142
页数：4
相关论文
共 32 条
[1]   Non-Natural Macrocyclic Inhibitors of Histone Deacetylases: Design, Synthesis, and Activity [J].
Auzzas, Luciana ;
Larsson, Andreas ;
Matera, Riccardo ;
Baraldi, Annamaria ;
Deschenes-Simard, Benoit ;
Giannini, Giuseppe ;
Cabri, Walter ;
Battistuzzi, Gianfranco ;
Gallo, Grazia ;
Ciacci, Andrea ;
Vesci, Loredana ;
Pisano, Claudio ;
Hanessian, Stephen .
JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (23) :8387-8399
[2]   Comparative application of antibody and gene array for expression profiling in human squamous cell lung carcinoma [J].
Bartling, B ;
Hofmann, HS ;
Boettger, T ;
Hansen, G ;
Burdach, S ;
Silber, RE ;
Simm, A .
LUNG CANCER, 2005, 49 (02) :145-154
[3]   Ubiquitin Proteasome System Stress Underlies Synergistic Killing of Ovarian Cancer Cells by Bortezomib and a Novel HDAC6 Inhibitor [J].
Bazzaro, Martina ;
Lin, Zhenhua ;
Santillan, Antonio ;
Lee, Michael K. ;
Wang, Mei-Cheng ;
Chan, Kwun C. ;
Bristow, Robert E. ;
Mazitschek, Ralph ;
Bradner, James ;
Roden, Richard B. S. .
CLINICAL CANCER RESEARCH, 2008, 14 (22) :7340-7347
[4]   Distinct pharmacological properties of second generation HDAC inhibitors with the benzamide or hydroxamate head group [J].
Beckers, Thomas ;
Burkhardt, Carmen ;
Wieland, Heike ;
Gimmnich, Petra ;
Ciossek, Thomas ;
Maier, Thomas ;
Sanders, Karl .
INTERNATIONAL JOURNAL OF CANCER, 2007, 121 (05) :1138-1148
[5]   Isoform-selective histone deacetylase inhibitors [J].
Bieliauskas, Anton V. ;
Pflum, Mary Kay H. .
CHEMICAL SOCIETY REVIEWS, 2008, 37 (07) :1402-1413
[6]   Structural requirements of HDAC inhibitors: SAHA analogs functionalized a lacent to the hydroxamic acid [J].
Bieliauskas, Anton V. ;
Weerasinghe, Sujith V. W. ;
Pflum, Mary Kay H. .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (08) :2216-2219
[7]   Structural origin of selectivity in class II-selective histone deacetylase inhibitors [J].
Estiu, Guillermina ;
Greenberg, Edward ;
Harrison, Christopher B. ;
Kwiatkowski, Nicholas P. ;
Mazitschek, Ralph ;
Bradner, James E. ;
Wiest, Olaf .
JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (10) :2898-2906
[8]   Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors [J].
Finnin M.S. ;
Donigian J.R. ;
Cohen A. ;
Richon V.M. ;
Rifkind R.A. ;
Marks P.A. ;
Breslow R. ;
Pavletich N.P. .
Nature, 1999, 401 (6749) :188-193
[9]   Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin [J].
Furumai, R ;
Komatsu, Y ;
Nishino, N ;
Khochbin, S ;
Yoshida, M ;
Horinouchi, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (01) :87-92
[10]   HDAC inhibitors overcome first hurdle [J].
Garber, Ken .
NATURE BIOTECHNOLOGY, 2007, 25 (01) :17-19
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