Home
Resources
Publications
Histone Deacetylase Inhibitors

Histone Deacetylase Inhibitors

Claude Monneret

Eur J Med Chem. 2005 Jan;40(1):1-13.

PMID: 15642405

Abstract:

Histones are small basic proteins that, by complexing wtih DNA, form the nucleosome core. Repetitive units of this nucleosome led to the chromatin in which all the human genome is packaged. Histones can be in one of the two antagonist forms, acetylated or deacetylated, equilibrium regulated by the corresponding enzymes, histone acetylases and histones deacetylases (HDACs). Inhibition of HDACs represents a new strategy in human cancer therapy since these enzymes play a fundamental role in regulating gene expression and chromatin assembly. They are potent inducers of growth arrest, differentiation and apoptosis of tumor cells. A wide variety of HDACs of both natural and synthetic origin has been reported. Except depsispeptide FK228, natural HDACs (trichostatin (TSA), depudecin, trapoxins, apicidins) as well as sodium butyrate, phenylbutyrate and suberoyl anilide hydroxamic acid (SAHA), while effective in vivo, are inefficient due to instability and low retention. Subsequently, synthetic analogs isolated from screening libraries (oxamflatin, scriptaid) were discovered as havind a common structure with TSA and SAHA: an hydroxamic acid zinc-binding group linked via a spacer (5 or 6 CH2) to a hydrophobic group. Design of a second generation of HDACs was based upon these data affording potent HDACs such as LAQ824 and PDX101 currently under phase I clinical trials. Simultaneously, synthetic benzamide-containing HDACs were reported and two of them, MS-275 and CI-994, have reached phase II and I clinical trials, respectively.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP112522642	CI−994		112522-64-2	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: