Histone deacetylase inhibitors: From target to clinical trials Journal Article
| Authors: | Kelly, W. K.; O'Connor, O. A.; Marks, P. A. |
| Article Title: | Histone deacetylase inhibitors: From target to clinical trials |
| Abstract: | Transformed cells, characterised by inappropriate cell proliferation, do not necessarily lose the capacity to undergo growth arrest under certain stimuli. DNA, genetic information, is packaged in chromatin proteins, for example, histones. The structure of chromatin may be altered by post-translational modifications (e.g., acetylation, phosphorylation, methylation and ubiquitylation) which play a role in regulating gene expression. Two groups of enzymes, histone deacetylases (HDACs) and acetyl transferases, determine the acetylation status of histones. This review focuses on compounds that inhibit HDAC activity. These agents have been shown to be active in vitro and in vivo in causing cancer cell growth arrest, differentiation and/or apoptosis. Several HDAC inhibitors are currently in clinical trials as anticancer agents and, in particular, hydroxamic acid-based HDAC inhibitors have shown activity against cancers at well-tolerated doses. |
| Keywords: | protein phosphorylation; unclassified drug; histone deacetylase inhibitor; clinical trial; drug activity; drug tolerability; fatigue; review; cancer growth; nonhuman; solid tumor; antineoplastic agents; drug targeting; capecitabine; antineoplastic agent; genetic analysis; neoplasm; neoplasms; cell proliferation; unindexed drug; edema; apoptosis; enzyme inhibition; lung non small cell cancer; animal experiment; animal model; in vivo study; cell differentiation; cancer cell culture; drug structure; in vitro study; enzyme inhibitor; enzyme activity; gene expression regulation; confusion; drug antagonism; hematologic malignancy; dna; protein processing; enzyme inhibitors; histone; cell transformation; chromatin; sulfonamide; glioblastoma; vorinostat; histone deacetylase inhibitors; hydroxamic acids; nausea and vomiting; malignant neoplastic disease; drug bioavailability; drug half life; dyspepsia; chromosome protein; neurologic disease; histones; histone deacetylases; retinoic acid; hydroxamic acid; clinical trials; peptides, cyclic; azacitidine; cyclopeptide; acyltransferase; protein methylation; valproic acid; histone deacetylase; 3 phenylsulfamoylcinnamohydroxamic acid; arylbutyric acid derivative; n (2 aminophenyl) 4 (3 pyridinylmethoxycarbonylaminomethyl)benzamide; pivaloyloxymethyl butyrate; 4 [n (2 hydroxyethyl) n [2 (3 indolyl)ethyl]aminomethyl]cinnamohydroxamic acid; 4 n acetyldinaline; cg 1521; trapoxin; trichostatin a; acetylation; chromatin structure; amide; growth inhibition; phenylacetic acid derivative; benzamide derivative; benzamides; suberoylanilide hydroxamic acid; mitosis inhibition; hydroxamic acid derivative; stimulus response; histone acetyl transferases; fr 901228; oxamflatin; butyric acid derivative; humans; human; depudecin; 7 [4 (4 cyanophenyl)phenoxy]heptanohydroxamic acid; apidicin; chlamydocin |
| Journal Title: | Expert Opinion on Investigational Drugs |
| Volume: | 11 |
| Issue: | 12 |
| ISSN: | 1354-3784 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 2002-12-01 |
| Start Page: | 1695 |
| End Page: | 1713 |
| Language: | English |
| DOI: | 10.1517/13543784.11.12.1695 |
| PUBMED: | 12457432 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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