Small Molecule Inhibitors of Zinc-dependent Histone Deacetylases

Neurotherapeutics

Volumn 10, Issue 4, 2013, Pages 589-604

  Wagner, Florence F ^a   Weyiwer, Michel ^a   Lewis, Michael C ^a   Holson, Edward B ^a  

^a BROAD INSTITUTE OF MIT AND HARVARD   (United States)

Author keywords

Acetylation; Chromatin; HDACs; Histone; Isoform selective; Zinc dependent hydrolases

Indexed keywords

APICIDIN; AZUMAMIDE E; BELINOSTAT; BRD 73954; BRD 9757; BUTYRIC ACID; CHLAMYDOCIN; DEPSIPEPTIDE; ENTINOSTAT; GIVINOSTAT; HISTONE DEACETYLASE; HISTONE DEACETYLASE 11; HISTONE DEACETYLASE 2; HISTONE DEACETYLASE 3; HISTONE DEACETYLASE 5; HISTONE DEACETYLASE INHIBITOR; HYDROXAMIC ACID; MOCETINOSTAT; PANDACOSTAT; PANOBINOSTAT; PCI 34051; QUISINOSTAT; RICOLINOSTAT; ROMIDEPSIN; SYNDAX; TACEDINALINE; TUBASTATIN A; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALPROATE SEMISODIUM; VALPROIC ACID; VORINOSTAT;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; AREA UNDER THE CURVE; ATAXIA; AUTISM; BIPOLAR DISORDER; BLOOD BRAIN BARRIER; CELLULAR DISTRIBUTION; CUTANEOUS T CELL LYMPHOMA; CYTOPLASM; DEPRESSION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG PENETRATION; DRUG POTENCY; EPILEPSY; FATIGUE; GENE EXPRESSION; HIPPOCAMPUS; HISTONE ACETYLATION; HUMAN; HUNTINGTON CHOREA; MAJOR DEPRESSION; MAXIMUM PLASMA CONCENTRATION; NAUSEA; NEUROLOGIC DISEASE; NONHUMAN; PRIORITY JOURNAL; PROTEIN LOCALIZATION; REVIEW; SCHIZOPHRENIA; SPINAL MUSCULAR ATROPHY; THROMBOCYTOPENIA;

ACETYLATION; HISTONE DEACETYLASE INHIBITORS; HISTONE DEACETYLASES; HISTONES; HUMANS;

EID: 84886259329     PISSN: 19337213     EISSN: 18787479     Source Type: Journal    
DOI: 10.1007/s13311-013-0226-1     Document Type: Review

References (100)

1. Khorasanizadeh S. The nucleosome: from genomic organization to genomic regulation. Cell 2004;116: 259-272.
2. Kornberg RD, Lorch Y. Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell 1999;98: 285-294.
3. Sengupta N, Seto E. Regulation of histone deacetylase activities. J Cell Biochem 2004;93: 57-67.
4. Chuang DM, Leng Y, Marinova Z, Kim HJ, Chiu CT. Multiple roles of HDAC inhibition in neurodegenerative conditions. Trends Neurosci 2009;32: 591-601.
5. de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB. Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 2003;370: 737-749.
6. Rodriquez M, Aquino M, Bruno I, et al. Chemistry and biology of chromatin remodeling agents: state of art and future perspectives of HDAC inhibitors. Curr Med Chem 2006;13: 1119-1139.
7. Fass DM, Kemp MM, Schroeder FA, et al. Histone acetylation and deacetylation. Epigenet Regul Epigenomics 2012;1: 515-561.
8. Peart MJ, Smyth GK, van Laar RK, et al. Identification and functional significance of genes regulated by structurally different histone deacetylase inhibitors. Proc Natl Acad Sci U S A 2005;102: 3697-3702.
9. Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 2006;5: 769-784.
10. Kazantsev AG, Thompson LM. Therapeutic application of histone deacetylase inhibitors for central nervous system disorders. Nat Rev Drug Discov 2008;7: 854-868.
11. Broide RS, Redwine JM, Aftahi N, et al. Distribution of histone deacetylases 1-11 in the rat brain. J Mol Neurosci 2007;31: 47-58.
12. Fischle W, Dequiedt F, Fillion M, et al. Human HDAC7 histone deacetylase activity is associated with HDAC3 in vivo. J Biol Chem 2001;276: 35826-35835.
13. Fischle W, Dequiedt F, Hendzel MJ, et al. Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR. Mol Cell 2002;9: 45-57.
14. Arrowsmith CH, Bountra C, Fish PV, Lee K, Schapira M. Epigenetic protein families: a new frontier for drug discovery. Nat Rev Drug Discov 2012;11: 384-400.
15. Kim T, Park JK, Kim HJ, Chung JH, Kim JW. Association of histone deacetylase genes with schizophrenia in Korean population. Psychiatry Res 2010;178: 266-269.
16. Tam GW, van de Lagemaat LN, Redon R, et al. Confirmed rare copy number variants implicate novel genes in schizophrenia. Biochem Soc Trans 2010;38: 445-451.
17. Guidotti A, Auta J, Davis JM, et al. Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study. Arch Gen Psychiatry 2000;57: 1061-1069.
18. Simonini MV, Camargo LM, Dong E, et al. The benzamide MS-275 is a potent, long-lasting brain region-selective inhibitor of histone deacetylases. Proc Natl Acad Sci U S A 2006;103: 1587-1592.
19. Graff J, Tsai L-H. The potential of HDAC inhibitors as cognitive enhancers. Annu Rev Pharmacol Toxicol 2013;53: 311-330.
20. Abel T, Zukin RS. Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders. Curr Opin Pharmacol 2008;8: 57-64.
21. Saha RN, Pahan K. HATs and HDACs in neurodegeneration: a tale of disconcerted acetylation homeostasis. Cell Death Diff 2006;13: 539-550.
22. Morris MJ, Monteggia LM. Unique functional roles for class I and class II histone deacetylases in central nervous system development and function. Int J Dev Neurosci 2013;31: 370-381.
23. Foley AG, Gannon S, Rombach-Mullan N, et al. Class I histone deacetylase inhibition ameliorates social cognition and cell adhesion molecule plasticity deficits in a rodent model of autism spectrum disorder. Neuropharmacology 2012;63: 750-760.
24. Machado-Vieira R, Ibrahim L, Zarate CA, Jr. Histone deacetylases and mood disorders: epigenetic programming in gene-environment interactions. CNS Neurosci Ther 2011;17: 699-704.
25. Guidotti A, Auta J, Chen Y, et al. Epigenetic GABAergic targets in schizophrenia and bipolar disorder. Neuropharmacology 2011;60: 1007-1016.
26. Grayson DR, Kundakovic M, Sharma RP. Is there a future for histone deacetylase inhibitors in the pharmacotherapy of psychiatric disorders? Mol Pharmacol 2010;77: 126-135.
27. Schmalbach S, Petri S. Histone deacetylation and motor neuron degeneration. CNS Neurol Disord Drug Targets 2010;9: 279-284.
28. Sleiman SF, Basso M, Mahishi L, et al. Putting the 'HAT' back on survival signalling: the promises and challenges of HDAC inhibition in the treatment of neurological conditions. Expert Opin Investig Drugs. 2009;18: 573-584.
29. Kozikowski AP, Chen Y, Subhasish T, et al. Searching for disease modifiers-PKC activation and HDAC inhibition-a dual drug approach to Alzheimer's disease that decreases Aβ production while blocking oxidative stress. Chem Med Chem 2009;4: 1095-1105.
30. Fraczek J, Vanhaecke T, Rogiers V. Toxicological and metabolic considerations for histone deacetylase inhibitors. Expert Opin Drug Metab Toxicol 2013;9: 441-457.
31. Bishton MJ, Harrison SJ, Martin BP, et al. Deciphering the molecular and biologic processes that mediate histone deacetylase inhibitor-induced thrombocytopenia. Blood 2011;117: 3658-3668.
32. Subramanian S, Bates SE, Wright JJ, Espinoza-Delgado I, Piekarz RL. Clinical toxicities of histone deacetylase inhibitors. Pharmaceuticals 2010;3: 2751-2767.
33. Wilting RH, Yanover E, Heideman MR, et al. Overlapping functions of HDAC1 and HDAC2 in cell cycle regulation and haematopoiesis. EMBO J 2010;29: 2586-2597.
34. Finnin MS, Donigian JR, Cohen A, et al. Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors. Nature 1999;401: 188-193.
35. Rosenberg G. The mechanisms of action of valproate in neuropsychiatric disorders: can we see the forest for the trees? Cell Mol Life Sci 2007;64: 2090-2103.
36. Bottomley MJ, Lo Surdo P, Di Giovine P, et al. Structural and functional analysis of the human HDAC4 catalytic domain reveals a regulatory structural zinc-binding domain. J Biol Chem 2008;283: 26694-26704.
37. Bressi JC, Jennings AJ, Skene R, et al. Exploration of the HDAC2 foot pocket: Synthesis and SAR of substituted N-(2-aminophenyl)benzamides. Bioorg Med Chem Lett 2010;20: 3142-3145.
38. Dowling DP, Gantt SL, Gattis SG, Fierke CA, Christianson DW. Structural studies of human histone deacetylase 8 and its site-specific variants complexed with substrate and inhibitors. Biochemistry 2008;47: 13554-13563.
39. Lobera M, Madauss KP, Pohlhaus DT, et al. Selective class IIa histone deacetylase inhibition via a nonchelating zinc-binding group. Nat Chem Biol 2013;9: 319-325.
40. Millard CJ, Watson PJ, Celardo I, et al. Class I HDACs share a common mechanism of regulation by inositol phosphates. Mol Cell 2013;51: 57-67.
41. Schuetz A, Min J, Allali-Hassani A, et al. Human HDAC7 harbors a Class IIa histone deacetylase-specific zinc binding motif and cryptic deacetylase activity. J Biol Chem 2008;283: 11355-11363.
42. Vannini A, Volpari C, Filocamo G, et al. Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor. Proc Natl Acad Sci U S A 2004;101: 15064-15069.
43. Vannini A, Volpari C, Gallinari P, et al. Substrate binding to histone deacetylases as shown by the crystal structure of the HDAC8-substrate complex. EMBO Rep 2007;8: 879-884.
44. Watson PJ, Fairall L, Santos GM, Schwabe JW. Structure of HDAC3 bound to co-repressor and inositol tetraphosphate. Nature 2012;481: 335-340.
45. Whitehead L, Dobler MR, Radetich B, et al. Human HDAC isoform selectivity achieved via exploitation of the acetate release channel with structurally unique small molecule inhibitors. Bioorg Med Chem 2011;19: 4626-4634.
46. Somoza JR, Skene RJ, Katz BA, et al. Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases. Structure 2004;12: 1325-1334.
47. Fass DM, Shah R, Ghosh B, et al. Short-chain HDAC inhibitors differentially affect vertebrate development and neuronal chromatin. ACS Med Chem Lett 2011;2: 39-42.
48. Bora-Tatar G, Dayangac-Erden D, Demir AS, et al. Molecular modifications on carboxylic acid derivatives as potent histone deacetylase inhibitors: Activity and docking studies. Bioorg Med Chem 2009;17: 5219-5228.
49. Loscher W, Nau H. Distribution of valproic acid and its metabolites in various brain areas of dogs and rats after acute and prolonged treatment. J Pharmacol Exp Ther 1983;226: 845-854.
50. Adkison KD, Shen DD. Uptake of valproic acid into rat brain is mediated by a medium-chain fatty acid transporter. J Pharmacol Exp Ther 1996;276: 1189-1200.
51. Cornford EM, Diep CP, Pardridge WM. Blood-brain barrier transport of valproic acid. J Neurochem 1985;44: 1541-1550.
52. Arts J, King P, Marien A, et al. JNJ-26481585, a novel "second-generation" oral histone deacetylase inhibitor, shows broad-spectrum preclinical antitumoral activity. Clin Cancer Res 2009;15: 6841-6851.
53. Bradner JE, West N, Grachan ML, et al. Chemical phylogenetics of histone deacetylases. Nat Chem Biol 2010;6: 238-243.
54. Haggarty SJ, Koeller KM, Wong JC, Grozinger CM, Schreiber SL. Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation. Proc Natl Acad Sci U S A 2003;100: 4389-4394.
55. Bieliauskas AV, Pflum MKH. Isoform-selective histone deacetylase inhibitors. Chem Soc Rev 2008;37: 1402-1413.
56. Santo L, Hideshima T, Kung AL, et al. Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma. Blood 2012;119: 2579-2589.
57. Chen Y, Lopez-Sanchez M, Savoy DN, et al. A series of potent and selective, triazolylphenyl-based histone deacetylases inhibitors with activity against pancreatic cancer cells and Plasmodium falciparum. J Med Chem 2008;51: 3437-3448.
58. Kozikowski AP, Tapadar S, Luchini DN, Kim KH, Billadeau DD. Use of the nitrile oxide cycloaddition (NOC) reaction for molecular probe generation: a new class of enzyme selective histone deacetylase inhibitors (HDACIs) showing picomolar activity at HDAC6. J Med Chem 2008;51: 4370-4373.
59. Smil DV, Manku S, Chantigny YA, et al. Novel HDAC6 isoform selective chiral small molecule histone deacetylase inhibitors. Bioorg Med Chem Lett 2009;19: 688-692.
60. Butler KV, Kalin J, Brochier C, et al. Rational Design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A. J Am Chem Soc 2010;132: 10842-10846.
61. Kalin JH, Butler KV, Akimova T, Hancock WW, Kozikowski AP. Second-generation histone deacetylase 6 inhibitors enhance the immunosuppressive effects of Foxp3+ T-regulatory cells. J Med Chem 2012;55: 639-651.
62. Wagner FF, Olson DE, Gale JP, et al. Potent and selective inhibition of histone deacetylase 6 (HDAC6) does not require a surface-binding motif. J Med Chem 2013;56: 1772-1776.
63. Krennhrubec K, Marshall BL, Hedglin M, Verdin E, Ulrich SM. Design and evaluation of 'Linkerless' hydroxamic acids as selective HDAC8 inhibitors. Bioorg Med Chem Lett 2007;17: 2874-2878.
64. Estiu G, West N, Mazitschek R, et al. On the inhibition of histone deacetylase 8. Bioorg Med Chem 2010;18: 4103-4110.
65. Balasubramanian S, Ramos J, Luo W, et al. A novel histone deacetylase 8 (HDAC8)-specific inhibitor PCI-34051 induces apoptosis in T-cell lymphomas. Leukemia 2008;22: 1026-1034.
66. Suzuki T, Ota Y, Ri M, et al. Rapid discovery of highly potent and selective inhibitors of histone deacetylase 8 using click chemistry to generate candidate libraries. J Med Chem 2012;55: 9562-9575.
67. Tang W, Luo T, Greenberg EF, Bradner JE, Schreiber SL. Discovery of histone deacetylase 8 selective inhibitors. Bioorg Med Chem Lett 2011;21: 2601-2605.
68. Olson DE, Wagner FF, Kaya T, et al. Discovery of the first histone deacetylase 6/8 dual inhibitors. J Med Chem 2013;56: 4816-4820.
69. Flipo M, Charton J, Hocine A, et al. Hydroxamates: relationships between structure and plasma stability. J Med Chem 2009;52: 6790-6802.
70. Palmieri D, Lockman PR, Thomas FC, et al. Vorinostat inhibits brain metastatic colonization in a model of triple-negative breast cancer and induces DNA double-strand breaks. Clin Cancer Res 2009;15: 6148-6157.
71. Patzke H, Albayya FP, Bollen E, et al. The novel histone deacetylase inhibitor EVP-0334 is pro cognitive in rats. Behavioral Epigenetics 2010; University Massachusetts Boston Campus Center Boston, MA, USA [Abstract].
72. Seidel C, Schnekenburger M, Dicato M, Diederich M. Histone deacetylase modulators provided by Mother Nature. Genes Nutr 2012;7: 357-367.
73. Furumai R, Matsuyama A, Kobashi N, et al. FK228 (depsipeptide) as a natural prodrug that inhibits class I histone deacetylases. Cancer Res 2002;62: 4916-4921.
74. Yurek-George A, Cecil AR, Mo AH, et al. The first biologically active synthetic analogues of FK228, the depsipeptide histone deacetylase inhibitor. J Med Chem 2007;50: 5720-5726.
75. Ying Y, Taori K, Kim H, Hong J, Luesch H. Total synthesis and molecular target of largazole, a histone deacetylase inhibitor. J Am Chem Soc 2008;130: 8455-8459.
76. Olsen CA, Ghadiri MR. Discovery of potent and selective histone deacetylase inhibitors via focused combinatorial libraries of cyclic alpha3beta-tetrapeptides. J Med Chem 2009;52: 7836-7846.
77. Darkin-Rattray SJ, Gurnett AM, Myers RW, et al. Apicidin: a novel antiprotozoal agent that inhibits parasite histone deacetylase. Proc Natl Acad Sci U S A 1996;93: 13143-13147.
78. Maulucci N, Chini MG, Di Micco S, et al. Molecular insights into azumamide E histone deacetylases inhibitory activity. J Am Chem Soc 2007;129: 3007-3012.
79. De Schepper S, Bruwiere H, Verhulst T, et al. Inhibition of histone deacetylases by chlamydocin induces apoptosis and proteasome-mediated degradation of survivin. J Pharmacol Exp Ther 2003;304: 881-888.
80. Furumai R, Komatsu Y, Nishino N, et al. Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin. Proc Natl Acad Sci U S A 2001;98: 87-92.
81. Auzzas L, Larsson A, Matera R, et al. Non-natural macrocyclic inhibitors of histone deacetylases: design, synthesis, and activity. J Med Chem. 2010;53: 8387-8399.
82. Riva L, Blaney SM, Dauser R, et al. Pharmacokinetics and cerebrospinal fluid penetration of CI-994 (N-acetyldinaline) in the nonhuman primate. Clin Cancer Res 2000;6: 994-997.
83. Hooker JM, Kim SW, Alexoff D, et al. Histone deacetylase inhibitor MS-275 exhibits poor brain penetration: pharmacokinetic studies of [11C]MS-275 using positron emission tomography. ACS Chem Neurosci 2010;1: 65-73.
84. Moradei OM, Mallais TC, Frechette S, et al. Novel aminophenyl benzamide-type histone deacetylase inhibitors with enhanced potency and selectivity. J Med Chem 2007;50: 5543-5546.
85. Heidebrecht RW, Jr., Chenard M, Close J, et al. Exploring the pharmacokinetic properties of phosphorus-containing selective HDAC 1 and 2 inhibitors (SHI-1: 2). Bioorg Med Chem Lett 2009;19: 2053-2058.
86. Witter DJ, Harrington P, Wilson KJ, et al. Optimization of biaryl Selective HDAC1&2 Inhibitors (SHI-1: 2). Bioorg Med Chem Lett. 2008;18: 726-731.
87. Methot JL, Chakravarty PK, Chenard M, et al. Exploration of the internal cavity of histone deacetylase (HDAC) with selective HDAC1/HDAC2 inhibitors (SHI-1: 2). Bioorg Med Chem Lett 2008;18: 973-978.
88. Boissinot M, Inman M, Hempshall A, et al. Induction of differentiation and apoptosis in leukaemic cell lines by the novel benzamide family histone deacetylase 2 and 3 inhibitor MI-192. Leuk Res 2012;36: 1304-1310.
89. Guan J-S, Haggarty SJ, Giacometti E, et al. HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 2009;459: 55-60.
90. McQuown SC, Barrett RM, Matheos DP, et al. HDAC3 is a critical negative regulator of long-term memory formation. J Neurosci 2011;31: 764-774.
91. Durham B. Novel histone deacetylase (HDAC) inhibitors with improved selectivity for HDAC2 and 3 protect against neural cell death. Biosci Horiz 2012;5: hzs003.
92. Chen Y, He R, Chen Y, et al. Studies of benzamide- and thiol-based histone deacetylase inhibitors in models of oxidative-stress-induced neuronal death: identification of some HDAC3-Selective Inhibitors. Chem Med Chem 2009;4: 842-852.
93. Rai M, Soragni E, Chou CJ, et al. Two new pimelic diphenylamide HDAC inhibitors induce sustained frataxin upregulation in cells from Friedreich's ataxia patients and in a mouse model. PLoS One 2010;5: e8825.
94. Chou CJ, Herman D, Gottesfeld JM. Pimelic diphenylamide 106 is a slow, tight-binding inhibitor of class I histone deacetylases. J Biol Chem 2008;283: 35402-35409.
95. Beconi M, Aziz O, Matthews K, et al. Oral administration of the pimelic diphenylamide HDAC inhibitor HDACi 4b is unsuitable for chronic inhibition of HDAC activity in the CNS in vivo. PLoS One 2012;7: e44498.
96. Malvaez M, McQuown Susan C, Rogge George A, et al. HDAC3-selective inhibitor enhances extinction of cocaine-seeking behavior in a persistent manner. Proc Natl Acad Sci U S A 2013;110: 2647-2652.
97. Ontoria JM, Altamura S, Di Marco A, et al. Identification of novel, selective, and stable inhibitors of class II histone deacetylases. Validation studies of the inhibition of the enzymatic activity of HDAC4 by small molecules as a novel approach for cancer therapy. J Med Chem 2009;52: 6782-6789.
98. Jones P, Bottomley MJ, Carfi A, et al. 2-Trifluoroacetylthiophenes, a novel series of potent and selective class II histone deacetylase inhibitors. Bioorg Med Chem Lett 2008;18: 3456-3461.
99. Wahhab A, Smil D, Ajamian A, et al Sulfamides as novel histone deacetylase inhibitors. Bioorg Med Chem Lett 2009;19: 336-340.
100. Ononye SN, VanHeyst MD, Oblak EZ, et al. Tropolones as lead-like natural products: the development of potent and selective histone deacetylase inhibitors. ACS Med Chem Lett 2013;4: 757-761.