Isoform-selective histone deacetylase inhibitors.

Histone deacetylase (HDAC) proteins are transcription regulators linked to cancer. As a result, multiple small molecule HDAC inhibitors are in various phases of clinical trials as anti-cancer drugs. The majority of HDAC inhibitors non-selectively influence the activities of eleven human HDAC isoforms, which are divided into distinct classes. This tutorial review focuses on the recent progress toward the identification of class-selective and isoform-selective HDAC inhibitors. The emerging trends suggest that subtle differences in the active sites of the HDAC isoforms can be exploited to dictate selectivity.

[1]  S. Haggarty,et al.  Multidimensional chemical genetic analysis of diversity-oriented synthesis-derived deacetylase inhibitors using cell-based assays. , 2003, Chemistry & biology.

[2]  Eric Verdin,et al.  Design and evaluation of 'Linkerless' hydroxamic acids as selective HDAC8 inhibitors. , 2007, Bioorganic & medicinal chemistry letters.

[3]  T. Yao,et al.  Molecular Cloning and Characterization of a Novel Histone Deacetylase HDAC10* , 2002, The Journal of Biological Chemistry.

[4]  Daniel Delorme,et al.  Novel hydroxamate and anilide derivatives as potent histone deacetylase inhibitors: synthesis and antiproliferative evaluation. , 2003, Current medicinal chemistry.

[5]  J. Adams,et al.  Kinetic and catalytic mechanisms of protein kinases. , 2001, Chemical reviews.

[6]  Stuart L Schreiber,et al.  Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[7]  P. Marks,et al.  Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors , 1999, Nature.

[8]  O. Wiest,et al.  Toward selective histone deacetylase inhibitor design: homology modeling, docking studies, and molecular dynamics simulations of human class I histone deacetylases. , 2005, Journal of medicinal chemistry.

[9]  Ivan V. Gregoretti,et al.  Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. , 2004, Journal of molecular biology.

[10]  P. Finn,et al.  Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors. , 2008, The Biochemical journal.

[11]  F. Dequiedt,et al.  Subtype selective substrates for histone deacetylases. , 2004, Journal of medicinal chemistry.

[12]  Ping Zhu,et al.  Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells , 2001, The EMBO journal.

[13]  A. Kral,et al.  Design of novel histone deacetylase inhibitors. , 2007, Bioorganic & medicinal chemistry letters.

[14]  J. Meinkoth,et al.  Histone Deacetylase Is a Target of Valproic Acid-Mediated Cellular Differentiation , 2004, Cancer Research.

[15]  Y. Hashimoto,et al.  Design, synthesis, and evaluation of cyclic amide/imide-bearing hydroxamic acid derivatives as class-selective histone deacetylase (HDAC) inhibitors. , 2006, Bioorganic & medicinal chemistry.

[16]  Yukihiro Itoh,et al.  Highly potent and selective histone deacetylase 6 inhibitors designed based on a small-molecular substrate. , 2006, Journal of medicinal chemistry.

[17]  M. Yoshida,et al.  Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[18]  M. V. Van Dyke,et al.  Parthenolide specifically depletes histone deacetylase 1 protein and induces cell death through ataxia telangiectasia mutated. , 2007, Chemistry & biology.

[19]  Michael J Meaney,et al.  Epigenetic programming by maternal behavior , 2004, Nature Neuroscience.

[20]  Suk Woo Nam,et al.  Increased expression of histone deacetylase 2 is found in human gastric cancer , 2005, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[21]  W. Sippl,et al.  Phenylalanine-containing hydroxamic acids as selective inhibitors of class IIb histone deacetylases (HDACs). , 2008, Bioorganic & medicinal chemistry.

[22]  Melissa Chenard,et al.  Optimization of biaryl Selective HDAC1&2 Inhibitors (SHI-1:2). , 2008, Bioorganic & medicinal chemistry letters.

[23]  O. Moradei,et al.  Novel aminophenyl benzamide-type histone deacetylase inhibitors with enhanced potency and selectivity. , 2007, Journal of medicinal chemistry.

[24]  Michael Rowley,et al.  A series of novel, potent, and selective histone deacetylase inhibitors. , 2006, Bioorganic & medicinal chemistry letters.

[25]  K. Garber.  HDAC inhibitors overcome first hurdle , 2007, Nature Biotechnology.

[26]  A. Ganesan,et al.  The first biologically active synthetic analogues of FK228, the depsipeptide histone deacetylase inhibitor. , 2007, Journal of medicinal chemistry.

[27]  Minoru Yoshida,et al.  FK228 (depsipeptide) as a natural prodrug that inhibits class I histone deacetylases. , 2002, Cancer research.

[28]  M. Janicot,et al.  R306465 is a novel potent inhibitor of class I histone deacetylases with broad-spectrum antitumoral activity against solid and haematological malignancies , 2007, British Journal of Cancer.

[29]  Ricardo Macarron,et al.  Identification of Novel Isoform-Selective Inhibitors within Class I Histone Deacetylases , 2003, Journal of Pharmacology and Experimental Therapeutics.

[30]  Yukihiro Itoh,et al.  Design, synthesis, structure--selectivity relationship, and effect on human cancer cells of a novel series of histone deacetylase 6-selective inhibitors. , 2007, Journal of medicinal chemistry.

[31]  G. Bifulco,et al.  Molecular insights into azumamide e histone deacetylases inhibitory activity. , 2007, Journal of the American Chemical Society.

[32]  Silvio Massa,et al.  Histone deacetylation in epigenetics: An attractive target for anticancer therapy , 2005, Medicinal research reviews.

[33]  A. Mai,et al.  Discovery of (aryloxopropenyl)pyrrolyl hydroxyamides as selective inhibitors of class IIa histone deacetylase homologue HD1-A. , 2003, Journal of medicinal chemistry.

[34]  K. Glaser,et al.  Expression and functional characterization of recombinant human HDAC1 and HDAC3. , 2004, Life sciences.

[35]  J. Mariadason,et al.  Drug-induced inactivation or gene silencing of class I histone deacetylases suppresses ovarian cancer cell growth: Implications for therapy , 2007, Cancer biology & therapy.

[36]  R. Ficner,et al.  Substrate and inhibitor specificity of class 1 and class 2 histone deacetylases. , 2006, Journal of biotechnology.

[37]  R. Ficner,et al.  Crystal structure of a bacterial class 2 histone deacetylase homologue. , 2005, Journal of molecular biology.

[38]  Stuart L Schreiber,et al.  Deacetylase enzymes: biological functions and the use of small-molecule inhibitors. , 2002, Chemistry & biology.

[39]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[40]  Tao Liu,et al.  Design and synthesis of a potent histone deacetylase inhibitor. , 2007, Journal of medicinal chemistry.

[41]  J. R. Somoza,et al.  Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases. , 2004, Structure.

[42]  M. Grunstein,et al.  25 years after the nucleosome model: chromatin modifications. , 2000, Trends in biochemical sciences.

[43]  R. De Francesco,et al.  Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[44]  L. Altucci,et al.  Class II (IIa)-selective histone deacetylase inhibitors. 1. Synthesis and biological evaluation of novel (aryloxopropenyl)pyrrolyl hydroxyamides. , 2005, Journal of medicinal chemistry.

[45]  J. Buggy,et al.  Interferon-α is able to maintain complete molecular remission induced by imatinib after its discontinuation , 2008, Leukemia.

[46]  S. Schreiber,et al.  Significance of HDAC6 regulation via estrogen signaling for cell motility and prognosis in estrogen receptor-positive breast cancer , 2005, Oncogene.

[47]  Sang Gyun Kim,et al.  Class I Histone Deacetylase-Selective Novel Synthetic Inhibitors Potently Inhibit Human Tumor Proliferation , 2004, Clinical Cancer Research.

[48]  A. Kral,et al.  The discovery of 6-amino nicotinamides as potent and selective histone deacetylase inhibitors. , 2007, Bioorganic & medicinal chemistry letters.

[49]  O. Wiest,et al.  On the function of the 14 A long internal cavity of histone deacetylase-like protein: implications for the design of histone deacetylase inhibitors. , 2004, Journal of medicinal chemistry.

[50]  P. Cohen.  Protein kinases — the major drug targets of the twenty-first century? , 2002, Nature reviews. Drug discovery.

[51]  S. Schreiber,et al.  Structural biasing elements for in-cell histone deacetylase paralog selectivity. , 2003, Journal of the American Chemical Society.

[52]  S. Minucci,et al.  Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer , 2006, Nature Reviews Cancer.

[53]  Minoru Yoshida,et al.  Cyclic tetrapeptides bearing a sulfhydryl group potently inhibit histone deacetylases. , 2003, Organic letters.

[54]  Joshua Close,et al.  Exploration of the internal cavity of histone deacetylase (HDAC) with selective HDAC1/HDAC2 inhibitors (SHI-1:2). , 2008, Bioorganic & medicinal chemistry letters.

[55]  L. Altucci,et al.  Bispyridinium dienes: histone deacetylase inhibitors with selective activities. , 2007, Journal of medicinal chemistry.

[56]  Gesine Hansen,et al.  Comparative application of antibody and gene array for expression profiling in human squamous cell lung carcinoma. , 2005, Lung cancer.

[57]  Minoru Yoshida,et al.  Chlamydocin analogs bearing carbonyl group as possible ligand toward zinc atom in histone deacetylases. , 2006, Bioorganic & medicinal chemistry.

[58]  T. Beckers,et al.  Distinct pharmacological properties of second generation HDAC inhibitors with the benzamide or hydroxamate head group , 2007, International journal of cancer.