Development of the pan-DAC inhibitor panobinostat (LBH589): Successes and challenges

被引：349

作者：

Atadja, Peter ^{[1
]}

机构：

[1] Novartis Inst Biomed Res, Cambridge, MA USA

来源：

CANCER LETTERS | 2009年 / 280卷 / 02期

关键词：

Panobinostat; LBH589; Histone deacetylase inhibitors; Pharmacodynamics; Hematologic malignancies; Solid tumors; HISTONE DEACETYLASE INHIBITOR; CHAPERONE FUNCTION; GENE-EXPRESSION; CANCER; HYPERACETYLATION; EPIGENOMICS; PROTEASOME; BORTEZOMIB; INDUCTION;

D O I：

10.1016/j.canlet.2009.02.019

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The histone deacetylase (HDAC) inhibitors are emerging as a highly useful class of anticancer agents that inhibit the enzyme HDAC involved in the deacetylation of histone and nonhistone cellular proteins. The HDAC inhibitor, panobinostat (LBH589, Novartis Pharmaceuticals), achieves potent inhibition of all HDAC enzymes implicated in cancer and has demonstrated potent anti-tumor activity in preclinical models and promising clinical efficacy in cancer patients. In this review we discuss the successes and challenges surrounding the development of panobinostat, focusing on its proposed mechanism of action, preclinical anti-tumor activity, and early clinical efficacy in hematologic and solid tumors. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

引用

页码：233 / 241

页数：9

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