Histone deacetylase inhibitors in cancer therapy: new compounds and clinical update of benzamide-type agents.
Histone deacetylase (HDAC) inhibitors constitute a novel and growing class of anticancer agents that function by altering intracellular patterns of histone acetylation, the so-called epigenetic "histone code," thereby producing changes in cell cycle arrest, differentiation, and/or apoptosis in tumor cells. This overview describes the chemistry and preliminary characterization of recently disclosed molecules in three major classes of HDAC inhibitors: hydroxamic acids, 2-amino- benzanilides, and cyclic peptides. In addition, results from recent clinical trials on isotype-selective HDAC inhibitors are reviewed. It is clear from the plethora of new molecules and the encouraging results from clinical trials that HDAC inhibitors hold a great deal of promise, particularly as add-on therapy, for the treatment of a variety of solid and hematologic cancers.
Moradei
Oscar
O
MethylGene Inc., Department of Medicinal Chemistry, 7220 Frederick-Banting, Montreal, QC, H4S 2A1, Canada. moradeio@methylgene.com
Vaisburg
Arkadii
A
Martell
Robert E
RE
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D051381:Rats; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001549:Benzamides; D056572:Histone Deacetylase Inhibitors