Melanoma Molecular Maps Projects



Title: List of histone deacetylase inhibitors (HDAI)
Legend: Acetylation and deacetylation of histones play a key role in transcription regulation. Acetylation status of histones and non-histone proteins is determined by histone deacetylases (HDAC; there are 18 HDAC, usually classified into four classes) and histone acetyl-transferases (HAT). HAT add and HDAC remove acetyl groups to lysine residues. In general, acetylation of histone promotes a more relaxed chromatin structure, allowing transcriptional activation. HDAC promote histone deacetylation > chromatin condensation > transcription repression. HDAC inhibitors (HDACI) selectively alter gene transcription, in part, by chromatin remodeling and by changes in the structure of proteins in transcription factor complexes. Further, HDAC have many non-histone proteins substrates such as hormone receptors, chaperone proteins and cytoskeleton proteins, which regulate cell proliferation and cell death. Inhibition of HDAC causes accumulation of acetylated forms of these proteins, altering their function. Thus, HDACI-induced cell death involves transcription-dependent and transcription-independent mechanisms. HDACI induce different phenotypes in various transformed cells, including growth arrest, activation of the extrinsic and/or intrinsic apoptotic pathways, autophagic cell death, reactive oxygen species (ROS)-induced cell death, mitotic cell death and senescence. In comparison, normal cells are relatively more resistant to HDACI-induced cell death. To date, several structural unrelated classes of HDACI demonstrating antitumor activity both in vitro and in vivo in animal models have been identified. These include: ABHA, AN-9 (Pivanex), Apicidine, Baceca, CBHA, CI-994, FK228 (depsipeptide), HDAC42, HTPB, ITF2357, LAQ-824, LBH589, MGCD0103, MS-275, Oxamflatin, PCI-24781, Phenylacetate, Phenylbutyrate (PBNA), PXD101, Pyroxamide, Scriptaid, Sodium butyrate, Trapoxin, Trichostatin-A, Trifluoromethyl ketone, Valproic acid, Vorinostat (Suberoylanilide hydroxamic acid, SAHA, Zolinza)
Author: The MMMP Team (updated: Dec 2007)

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