Histone deacetylase inhibitors with a primary amide zinc binding group display antitumor activity in xenograft model

被引：27

作者：

Attenni, Barbara ^{[1
]}

Ontoria, Jesus M. ^{[1
]}

Cruz, Jonathan C. ^{[2
]}

Rowley, Michael ^{[1
]}

Schultz-Fademrecht, Carsten ^{[1
]}

Steinkuehler, Christian ^{[1
]}

Jones, Philip ^{[1
]}

机构：

[1] IRBM Merck Res Labs, I-00040 Rome, Italy

[2] MRL Boston, Boston, MA 02115 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 11期

关键词：

HDAC inhibitors; Primary carboxamide; Zinc binding group; POTENT; SERIES; AGENT;

D O I：

10.1016/j.bmcl.2009.04.011

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Histone deacetylase (HDAC) inhibition causes hyperacetylation of histones leading to differentiation, growth arrest and apoptosis of malignant cells, representing a new strategy in cancer therapy. Many of the known HDAC inhibitors (HDACi) that are in clinical trials possess a hydroxamic acid, that is a strong Zn(2+) binding group, thereby inhibiting some of the class I and class II isoforms. Herein we describe the identification of a selective class I HDAC inhibitor bearing a primary carboxamide moiety as zinc binding group. This HDACi displays good antiproliferative activity against multiple cancer cell lines, and demonstrates efficacy in a xenograft model comparable to vorinostat. (C) 2009 Elsevier Ltd. All rights reserved.

引用

收藏

页码：3081 / 3084

页数：4

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