The Search for Potent, Small-Molecule HDACIs in Cancer Treatment: A Decade After Vorinostat

Medicinal Research Reviews

Volumn 37, Issue 6, 2017, Pages 1373-1428

  Zagni, Chiara ^a   Floresta, Giuseppe ^a   Monciino, Giulia ^a   Rescifina, Antonio ^a  

^a UNIVERSITY OF CATANIA   (Italy)

Author keywords

benzamides; cyclic peptides; epigenetics; histone deacetylase inhibitors; hydroxamic acids

Indexed keywords

BENZAMIDE DERIVATIVE; HISTONE DEACETYLASE; HYDROXAMIC ACID; MACROCYCLIC COMPOUND; VORINOSTAT; HISTONE DEACETYLASE INHIBITOR;

CANCER CHEMOTHERAPY; CATALYST; CUTANEOUS T CELL LYMPHOMA; DRUG CLASSIFICATION; DRUG MECHANISM; DRUG POTENCY; DRUG STABILITY; HUMAN; MOLECULAR MODEL; NONHUMAN; PHARMACOPHORE; REVIEW; STRUCTURE ACTIVITY RELATION; ANIMAL; CLINICAL TRIAL (TOPIC); ENZYMOLOGY; MOLECULAR LIBRARY; NEOPLASM; PHARMACOLOGY; THERAPEUTIC USE;

ANIMALS; CLINICAL TRIALS AS TOPIC; HISTONE DEACETYLASE INHIBITORS; HUMANS; HYDROXAMIC ACIDS; NEOPLASMS; SMALL MOLECULE LIBRARIES;

EID: 85013271782     PISSN: 01986325     EISSN: 10981128     Source Type: Journal    
DOI: 10.1002/med.21437     Document Type: Review

References (196)

1. Heerboth S, Lapinska K, Snyder N, Leary M, Rollinson S, Sarkar S. Use of epigenetic drugs in disease: An overview. Genet Epigenet 2014;6:9–19.
2. Zagni C, Chiacchio U, Rescifina A. Histone methyltransferase inhibitors: Novel epigenetic agents for cancer treatment. Curr Med Chem 2013;20(2):167–185.
3. Jones PA, Baylin SB. The epigenomics of cancer. Cell 2007;128(4):683–692.
4. Kornberg RD. Chromatin structure: A repeating unit of histones and DNA. Science 1974;184(4139):868–871.
5. Smith BC, Denu JM. Chemical mechanisms of histone lysine and arginine modifications. Biochim Biophys Acta 2009;1789(1):45–57.
6. Kouzarides T. Chromatin modifications and their function. Cell 2007;128(4):693–705.
7. Roth SY, Denu JM, Allis CD. Histone acetyltransferases. Annu Rev Biochem 2001;70:81–120.
8. Bose P, Dai Y, Grant S. Histone deacetylase inhibitor (HDACI) mechanisms of action: Emerging insights. Pharmacol Ther 2014;143(3):323–336.
9. Izzo A, Schneider R. Chatting histone modifications in mammals. Brief Funct Genomics 2010;9(5-6):429–443.
10. Delcuve GP, Khan DH, Davie JR. Roles of histone deacetylases in epigenetic regulation: Emerging paradigms from studies with inhibitors. Clin Epigenetics 2012;4(1):5.
11. de Ruijter AJM, van Gennip AH, Caron HN, Kemp S, van Kuilenburg ABP. Histone deacetylases (HDACs): Characterization of the classical HDAC family. Biochem J 2003;370:737–749.
12. Behera J, Jayprakash V, Sinha BN. Histone deacetylase inhibitors: A Review on class-I specific inhibition. Mini-Rev Med Chem 2015;15(9):731–750.
13. Di Giorgio E, Gagliostro E, Brancolini C. Selective class IIa HDAC inhibitors: Myth or reality. Cell Mol Life Sci 2015;72(1):73–86.
14. Martin M, Kettmann R, Dequiedt F. Class IIa histone deacetylases: Regulating the regulators. Oncogene 2007;26(37):5450–5467.
15. Liu YJ, Peng LR, Seto E, Huang SM, Qiu Y. Modulation of histone deacetylase 6 (HDAC6) nuclear import and tubulin deacetylase activity through acetylation. J Biol Chem 2012;287(34):29168–29174.
16. Marks PA. Histone deacetylase inhibitors: a chemical genetics approach to understanding cellular functions. Biochim Biophys Acta 2010;1799(10-12):717–725.
17. Gregoretti IV, Lee Y-M, Goodson HV. Molecular evolution of the histone deacetylase family: Functional implications of phylogenetic analysis. J Mol Biol 2004;338(1):17–31.
18. Morioka H, Ishihara M, Takezawa M, Shibai H, Komoda Y. (+)-Trichostatin A, a potent differentiation inducer of friend leukemia cells. Agric Biol Chem 1988;52(1):251–253.
19. Yoshida M, Nomura S, Beppu T. Effects of trichostatins on differentiation of murine erythroleukemia cells. Cancer Res 1987;47(14):3688–3691.
20. Hayashi A, Horiuchi A, Kikuchi N, Hayashi T, Fuseya C, Suzuki A, Konishi I, Shiozawa T. Type-specific roles of histone deacetylase (HDAC) overexpression in ovarian carcinoma: HDAC1 enhances cell proliferation and HDAC3 stimulates cell migration with downregulation of E-cadherin. Int J Cancer 2010;127(6):1332–1346.
21. Guan RJ, Ford HL, Fu Y, Li Y, Shaw LM, Pardee AB. Drg-1 as a differentiation-related, putative metastatic suppressor gene in human colon cancer. Cancer Res 2000;60(3):749–755.
22. Kollar J, Frecer V. Selective inhibitors of zinc-dependent histone deacetylases. Therapeutic targets relevant to cancer. Curr Pharm Des 2015;21(11):1472–1502.
23. Finnin MS, Donigian JR, Cohen A, Richon VM, Rifkind RA, Marks PA, Breslow R, Pavletich NP. Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors. Nature 1999;401(6749):188–193.
24. Duvic M, Talpur R, Ni X, Zhang C, Hazarika P, Kelly C, Chiao JH, Reilly JF, Ricker JL, Richon VM, Frankel SR. Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL). Blood 2007;109(1):31–39.
25. Zwergel C, Valente S, Jacob C, Mai A. Emerging approaches for histone deacetylase inhibitor drug discovery. Exp Opin Drug Discov 2015;10(6):599–613.
26. Giannini G, Cabri W, Fattorusso C, Rodriquez M. Histone deacetylase inhibitors in the treatment of cancer: Overview and perspectives. Future Med Chem 2012;4(11):1439–1460.
27. Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 2006;5(9):769–784.
28. Dokmanovic M, Marks PA. Prospects: Histone deacetylase inhibitors. J Cell Biochem 2005;96(2):293–304.
29. Piekarz RL, Sackett DL, Bates SE. Histone deacetylase inhibitors and demethylating agents: Clinical development of histone deacetylase inhibitors for cancer therapy. Cancer J 2007;13(1):30–39.
30. Yu C, Rahmani M, Conrad D, Subler M, Dent P, Grant S. The proteasome inhibitor bortezomib interacts synergistically with histone deacetylase inhibitors to induce apoptosis in Bcr/Abl+ cells sensitive and resistant to STI571. Blood 2003;102(10):3765–3774.
31. Gray SG. Epigenetic treatment of neurological disease. Epigenomics 2011;3(4):431–450.
32. Dinarello CA. Anti-inflammatory agents: Present and future. Cell 2010;140(6):935–950.
33. McKinsey TA. Therapeutic potential for HDAC inhibitors in the heart. Annu Rev Pharmacol Toxicol 2012;52:303–319.
34. Shakespear MR, Halili MA, Irvine KM, Fairlie DP, Sweet MJ. Histone deacetylases as regulators of inflammation and immunity. Trends Immunol 2011;32(7):335–343.
35. Penney J, Tsai LH. Histone deacetylases in memory and cognition. Sci Signal 2014;7(355):1–7.
36. Sharma RP, Grayson DR, Gavin DP. Histone deactylase 1 expression is increased in the prefrontal cortex of schizophrenia subjects: Analysis of the National Brain Databank microarray collection. Schizophr Res 2008;98(1-3):111–117.
37. Covington HE, Maze I, LaPlant QC, Vialou VF, Ohnishi YN, Berton O, Fass DM, Renthal W, Rush AJ, Wu EY, Ghose S, Krishnan V, Russo SJ, Tamminga C, Haggarty SJ, Nestler EJ. Antidepressant actions of histone deacetylase inhibitors. J Neurosci 2009;29(37):11451–11460.
38. Liao XD, Haldar SM, Lu YA, Jeyaraj D, Paruchuri K, Nahori M, Cui YJ, Kaestner KH, Jain MK. Kruppel-like factor 4 regulates pressure-induced cardiac hypertrophy. J Mol Cell Cardiol 2010;49(2):334–338.
39. Abend A, Kehat I. Histone deacetylases as therapeutic targets – From cancer to cardiac disease. Pharmacol Ther 2015;147:55–62.
40. Cheng J, Qin J, Guo S, Qiu H, Zhong Y. Design, synthesis and evaluation of novel HDAC inhibitors as potential antitumor agents. Bioorg Med Chem Lett 2014;24(19):4768–4772.
41. Rossi C, Porcelloni M, D'Andrea P, Fincham CI, Ettorre A, Mauro S, Squarcia A, Bigioni M, Parlani M, Nardelli F, Binaschi M, Maggi CA, Fattori D. Alkyl piperidine and piperazine hydroxamic acids as HDAC inhibitors. Bioorg Med Chem Lett 2011;21(8):2305–2308.
42. Rossi C, Fincham CI, D'Andrea P, Porcelloni M, Ettorre A, Mauro S, Bigioni M, Binaschi M, Maggi CA, Nardelli F, Parlani M, Fattori D. 4-N-Hydroxy-4-[1-(sulfonyl)piperidin-4-yl]-butyramides as HDAC inhibitors. Bioorg Med Chem Lett 2011;21(22):6767–6769.
43. Oanh DTK, Hai HV, Park SH, Kim H-J, Han B-W, Kim H-S, Hong J-T, Han S-B, Hue VTM, Nam N-H. Benzothiazole-containing hydroxamic acids as histone deacetylase inhibitors and antitumor agents. Bioorg Med Chem Lett 2011;21(24):7509–7512.
44. Pabba C, Gregg BT, Kitchen DB, Chen ZJ, Judkins A. Design and synthesis of aryl ether and sulfone hydroxamic acids as potent histone deacetylase (HDAC) inhibitors. Bioorg Med Chem Lett 2011;21(1):324–328.
45. Thaler F, Varasi M, Carenzi G, Colombo A, Abate A, Bigogno C, Boggio R, Carrara S, Cataudella T, Dal Zuffo R, Reali V, Vultaggio S, Dondio G, Gagliardi S, Minucci S, Mercurio C. Spiro[chromane-2,4′-piperidine]-based histone deacetylase inhibitors with improved in vivo activity. ChemMedChem 2012;7(4):709–721.
46. Choi E, Lee C, Park JE, Seo JJ, Cho M, Kang JS, Kim HM, Park S-K, Lee K, Han G. Structure and property based design, synthesis and biological evaluation of γ-lactam based HDAC inhibitors. Bioorg Med Chem Lett 2011;21(4):1218–1221.
47. Kim HM, Hong SH, Kim MS, Lee CW, Kang JS, Lee K, Park S-K, Han JW, Lee HY, Choi Y, Kwon HJ, Han G. Modification of cap group in delta-lactam-based histone deacetylase (HDAC) inhibitors. Bioorg Med Chem Lett 2007;17(22):6234–6238.
48. Kim HM, Lee K, Park BW, Ryu DK, Kim K, Lee CW, Park S-K, Han JW, Lee HY, Lee HY, Han G. Synthesis, enzymatic inhibition, and cancer cell growth inhibition of novel delta-lactam-based histone deacetylase (HDAC) inhibitors. Bioorg Med Chem Lett 2006;16(15):4068–4070.
49. Yoon HC, Choi E, Park JE, Cho M, Seo JJ, Oh SJ, Kang JS, Kim HM, Park S-K, Lee K, Han G. Property based optimization of δ-lactam HDAC inhibitors for metabolic stability. Bioorg Med Chem Lett 2010;20(22):6808–6811.
50. Lee C, Choi E, Cho M, Lee B, Oh SJ, Park S-K, Lee K, Kim HM, Han G. Structure and property based design, synthesis and biological evaluation of γ-lactam based HDAC inhibitors: Part II. Bioorg Med Chem Lett 2012;22(12):4189–4192.
51. Hou J, Feng C, Li Z, Fang Q, Wang H, Gu G, Shi Y, Liu P, Xu F, Yin Z, Shen J, Wang P. Structure-based optimization of click-based histone deacetylase inhibitors. Eur J Med Chem 2011;46(8):3190–3200.
52. Shultz M, Fan J, Chen C, Cho YS, Davis N, Bickford S, Buteau K, Cao X, Holmqvist M, Hsu M, Jiang L, Liu G, Lu Q, Patel C, Suresh JR, Selvaraj M, Urban L, Wang P, Yan-Neale Y, Whitehead L, Zhang H, Zhou L, Atadja P. The design, synthesis and structure–activity relationships of novel isoindoline-based histone deacetylase inhibitors. Bioorg Med Chem Lett 2011;21(16):4909–4912.
53. Spencer J, Amin J, Wang M, Packham G, Alwi SSS, Tizzard GJ, Coles SJ, Paranal RM, Bradner JE, Heightman TD. Synthesis and biological evaluation of JAHAs: Ferrocene-based histone deacetylase inhibitors. ACS Med Chem Lett 2011;2(5):358–362.
54. Wang H, Yu N, Chen D, Lee KC, Lye PL, Chang JW, Deng W, Ng MC, Lu T, Khoo ML, Poulsen A, Sangthongpitag K, Wu X, Hu C, Goh KC, Wang X, Fang L, Goh KL, Khng HH, Goh SK, Yeo P, Liu X, Bonday Z, Wood JM, Dymock BW, Kantharaj E, Sun ET. Discovery of (2E)-3-{2-butyl-1-[2-(diethylamino)ethyl]-1H-benzimidazol-5-yl}-N-hydroxyacrylami de (SB939), an orally active histone deacetylase inhibitor with a superior preclinical profile. J Med Chem 2011;54(13):4694–4720.
55. Wang HS, Yu NF, Song HY, Chen DZ, Zou Y, Deng WP, Lye PL, Chang J, Ng M, Blanchard S, Sun ET, Sangthongpitag K, Wang XK, Goh KC, Wu XF, Khng HH, Fang LJ, Goh SK, Ong WC, Bonday Z, Stuenkel W, Poulsen A, Entzeroth M. N-Hydroxy-1,2-disubstituted-1H-benzimidazol-5-yl acrylamides as novel histone deacetylase inhibitors: Design, synthesis, SAR studies, and in vivo antitumor activity. Bioorg Med Chem Lett 2009;19(5):1403–1408.
56. Razak ARA, Hotte SJ, Siu LL, Chen EX, Hirte HW, Powers J, Walsh W, Stayner LA, Laughlin A, Novotny-Diermayr V, Zhu J, Eisenhauer EA. Phase I clinical, pharmacokinetic and pharmacodynamic study of SB939, an oral histone deacetylase (HDAC) inhibitor, in patients with advanced solid tumours. Br J Cancer 2011;104(5):756–762.
57. Ning CQ, Bi YJ, He YJ, Huang WY, Liu LF, Li Y, Zhang SH, Liu XY, Yu NF. Design, synthesis and biological evaluation of di-substituted cinnamic hydroxamic acids bearing urea/thiourea unit as potent histone deacetylase inhibitors. Bioorg Med Chem Lett 2013;23(23):6432–6435.
58. Sandhu P, Andrews PA, Baker MP, Koeplinger KA, Soli ED, Miller T, Baillie TA. Disposition of vorinostat, a novel histone deacetylase inhibitor and anticancer agent, in preclinical species. Drug Metab Lett 2007;1(2):153–161.
59. Wang T, Sepulveda M, Gonzales P, Gately S. Identification of novel HDAC inhibitors through cell based screening and their evaluation as potential anticancer agents. Bioorg Med Chem Lett 2013;23(17):4790–4793.
60. Novotny-Diermayr V, Sangthongpitag K, Hu CY, Wu XF, Sausgruber N, Yeo P, Greicius G, Pettersson S, Liang AL, Loh YK, Bonday Z, Goh KC, Hentze H, Hart S, Wang HS, Ethirajulu K, Wood JM. SB939, a novel potent and orally active histone deacetylase inhibitor with high tumor exposure and efficacy in mouse models of colorectal cancer. Mol Cancer Ther 2010;9(3):642–652.
61. Nam NH, Huong TL, Dung DTM, Dung PTP, Oanh DTK, Quyen D, Thao LT, Park SH, Kim KR, Han BW, Yun J, Kang JS, Kim Y, Han SB. Novel isatin-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents. Eur J Med Chem 2013;70:477–486.
62. Taddei M, Cini E, Giannotti L, Giannini G, Battistuzzi G, Vignola D, Vesci L, Cabri W. Lactam based 7-amino suberoylamide hydroxamic acids as potent HDAC inhibitors. Bioorg Med Chem Lett 2014;24(1):61–64.
63. Andrews KT, Tran TN, Lucke AJ, Kahnberg P, Le GT, Boyle GM, Gardiner DL, Skinner-Adams TS, Fairlie DP. Potent antimalarial activity of histone deacetylase inhibitor analogues. Antimicrob Agents Chemother 2008;52(4):1454–1461.
64. Giannini G, Battistuzzi G, Vignola D. Hydroxamic acid based histone deacetylase inhibitors with confirmed activity against the malaria parasite. Bioorg Med Chem Lett 2015;25(3):459–461.
65. Giannini G, Vesci L, Battistuzzi G, Vignola D, Milazzo FM, Guglielmi MB, Barbarino M, Santaniello M, Fantò N, Mor M, Rivara S, Pala D, Taddei M, Pisano C, Cabri W. ST7612AA1, a thioacetate-ω(γ-lactam carboxamide) derivative selected from a novel generation of oral HDAC inhibitors. J Med Chem 2014;57(20):8358–8377.
66. Vesci L, Bernasconi E, Milazzo FM, De Santis R, Gaudio E, Kwee I, Rinaldi A, Pace S, Carollo V, Giannini G, Bertoni F. Preclinical antitumor activity of ST7612AA1: a new oral thiol-based histone deacetylase (HDAC) inhibitor. Oncotarget 2015;6(8):5735–5748.
67. Hotez PJ, Kamath A. Neglected tropical diseases in sub-Saharan Africa: Review of their prevalence, distribution, and disease burden. PLoS Negl Trop Dis 2009;3(8):414–421.
68. Oger F, Dubois F, Caby S, Noel C, Cornette J, Bertin B, Capron M, Pierce RJ. The class I histone deacetylases of the platyhelminth parasite Schistosoma mansoni. Biochem Biophys Res Commun 2008;377(4):1079–1084.
69. Kannan S, Melesina J, Hauser AT, Chakrabarti A, Heimburg T, Schmidtkunz K, Walter A, Marek M, Pierce RJ, Romier C, Jung M, Sippl W. Discovery of inhibitors of Schistosoma mansoni HDAC8 by combining homology modeling, virtual screening, and in vitro validation. J Chem Inf Model 2014;54(10):3005–3019.
70. Heinnburg T, Chakrabarti A, Lancelot J, Marek M, Melesina J, Hauser AT, Shaik TB, Duclaud S, Robaa D, Erdmann F, Schmidt M, Romier C, Pierce RJ, Jung M, Sippl W. Structure-based design and synthesis of novel inhibitors targeting HDAC8 from Schistosoma mansoni for the treatment of schistosomiasis. J Med Chem 2016;59(6):2423–2435.
71. Blackburn C, Barrett C, Chin J, Garcia K, Gigstad K, Gould A, Gutierrez J, Harrison S, Hoar K, Lynch C, Rowland RS, Tsu C, Ringeling J, Xu H. Potent histone deacetylase inhibitors derived from 4-(aminomethyl)-N-hydroxybenzamide with high selectivity for the HDAC6 isoform. J Med Chem 2013;56(18):7201–7211.
72. Blackburn C, Barrett C, Brunson M, Chin J, England D, Garcia K, Gigstad K, Gould A, Gutierrez J, Hoar K, Rowland RS, Tsu C, Ringeling J, Wager K, Xu H. Histone deacetylase inhibitors derived from 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine and related heterocycles selective for the HDAC6 isoform. Bioorg Med Chem Lett 2014;24(23):5450–5454.
73. Lai M-J, Huang H-L, Pan S-L, Liu Y-M, Peng C-Y, Lee H-Y, Yeh T-K, Huang P-H, Teng C-M, Chen C-S, Chuang H-Y, Liou J-P. Synthesis and biological evaluation of 1-arylsulfonyl-5-(N-hydroxyacrylamide)indoles as potent histone deacetylase inhibitors with antitumor activity in vivo. J Med Chem 2012;55(8):3777–3791.
74. Zhang Y, Fang H, Feng J, Jia Y, Wang X, Xu W. Discovery of a tetrahydroisoquinoline-based hydroxamic acid derivative (ZYJ-34c) as histone deacetylase inhibitor with potent oral antitumor activities. J Med Chem 2011;54(15):5532–5539.
75. Lee H-Y, Yang C-R, Lai M-J, Huang H-L, Hsieh Y-L, Liu Y-M, Yeh T-K, Li Y-H, Mehndiratta S, Teng C-M, Liou J-P. 1-Arylsulfonyl-5-(N-hydroxyacrylamide)indolines histone deacetylase inhibitors are potent cytokine release suppressors. ChemBioChem 2013;14(10):1248–1254.
76. Huang H-L, Huang H-L, Lee H-Y, Tsai A-C, Peng C-Y, Lai M-J, Wang J-C, Pan S-L, Teng C-M, Liou J-P. Anticancer activity of MPT0E028, a novel potent histone deacetylase inhibitor, in human colorectal cancer HCT116 cells in vitro and in vivo. PLoS One 2012;7(8):e43645.
77. Mehndiratta S, Hsieh Y-L, Liu Y-M, Wang AW, Lee H-Y, Liang L-Y, Kumar S, Teng C-M, Yang C-R, Liou J-P. Indole-3-ethylsulfamoylphenylacrylamides: Potent histone deacetylase inhibitors with anti-inflammatory activity. Eur J Med Chem 2014;85:468–479.
78. Maren TH. Relations between structure and biological activity of sulfonamides. Annu Rev Pharmacol Toxicol 1976;16(1):309–327.
79. Liu Y-M, Lee H-Y, Chen C-H, Lee C-H, Wang L-T, Pan S-L, Lai M-J, Yeh T-K, Liou J-P. 1-Arylsulfonyl-5-(N-hydroxyacrylamide)tetrahydroquinolines as potent histone deacetylase inhibitors suppressing the growth of prostate cancer cells. Eur J Med Chem 2015;89:320–330.
80. Sun Q, Yao Y, Liu C, Li H, Yao H, Xue X, Liu J, Tu Z, Jiang S. Design, synthesis, and biological evaluation of novel histone deacetylase 1 inhibitors through click chemistry. Bioorg Med Chem Lett 2013;23(11):3295–3299.
81. Yao Y, Liao C, Li Z, Wang Z, Sun Q, Liu C, Yang Y, Tu Z, Jiang S. Design, synthesis, and biological evaluation of 1,3-disubstituted-pyrazole derivatives as new class I and IIb histone deacetylase inhibitors. Eur J Med Chem 2014;86:639–652.
82. Bruserud Ø, Stapnes C, Ersvaer E, Gjertsen BT, Ryningen A. Histone deacetylase inhibitors in cancer treatment: A review of the clinical toxicity and the modulation of gene expression in cancer cell. Curr Pharm Biotechnol 2007;8(6):388–400.
83. Khan N, Jeffers M, Kumar S, Hackett C, Boldog F, Khramtsov N, Qian X, Mills E, Berghs SC, Carey N, Finn PW, Collins LS, Tumber A, Ritchie JW, Jensen PB, Lichenstein HS, Sehested M. Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors. Biochem J 2008;409(2):581–589.
84. Beckers T, Burkhardt C, Wieland H, Gimmnich P, Ciossek T, Maier T, Sanders K. Distinct pharmacological properties of second generation HDAC inhibitors with the benzamide or hydroxamate head group. Int J Cancer 2007;121(5):1138–1148.
85. Stolfa DA, Stefanachi A, Gajer JM, Nebbioso A, Altucci L, Cellamare S, Jung M, Carotti A. Design, synthesis, and biological evaluation of 2-aminobenzanilide derivatives as potent and selective HDAC inhibitors. ChemMedChem 2012;7(7):1256–1266.
86. Moradei OM, Mallais TC, Frechette S, Paquin I, Tessier PE, Leit SM, Fournel M, Bonfils C, Trachy-Bourget M-C, Liu J, Yan TP, Lu A-H, Rahil J, Wang J, Lefebvre S, Li Z, Vaisburg AF, Besterman JM. Novel aminophenyl benzamide-type histone deacetylase inhibitors with enhanced potency and selectivity. J Med Chem 2007;50(23):5543–5546.
87. Witter DJ, Harrington P, Wilson KJ, Chenard M, Fleming JC, Haines B, Kral AM, Secrist JP, Miller TA. Optimization of biaryl selective HDAC1&2 inhibitors (SHI-1:2). Bioorg Med Chem Lett 2008;18(2):726–731.
88. Li Y, Zhou Y, Qian P, Wang Y, Jiang F, Yao Z, Hu W, Zhao Y, Li S. Design, synthesis and bioevalution of novel benzamides derivatives as HDAC inhibitors. Bioorg Med Chem Lett 2013;23(1):179–182.
89. Li Y, Wang Y, Xie N, Xu M, Qian P, Zhao Y, Li S. Design, synthesis and antiproliferative activities of novel benzamides derivatives as HDAC inhibitors. Eur J Med Chem 2015;100:270–276.
90. Zhao B, He TL. Chidamide, a histone deacetylase inhibitor, functions as a tumor inhibitor by modulating the ratio of Bax/Bcl-2 and P21 in pancreatic cancer. Oncol Rep 2015;33(1):304–310.
91. Gong K, Xie J, Yi H, Li WH. CS055 (Chidamide/HBI-8000), a novel histone deacetylase inhibitor, induces G(1) arrest, ROS-dependent apoptosis and differentiation in human leukaemia cells. Biochem J 2012;443:735–746.
92. Wang EC, Min YZ, Palm RC, Fiordalisi JJ, Wagner KT, Hyder N, Cox AD, Caster JM, Tian X, Wang AZ. Nanoparticle formulations of histone deacetylase inhibitors for effective chemoradiotherapy in solid tumors. Biomaterials 2015;51:208–215.
93. el Bahhaj F, Denis I, Pichavant L, Delatouche R, Collette F, Linot C, Pouliquen D, Gregoire M, Heroguez V, Blanquart C, Bertrand P. Histone deacetylase inhibitors delivery using nanoparticles with intrinsic passive tumor targeting properties for tumor therapy. Theranostics 2016;6(6):795–807.
94. Mwakwari SC, Patil V, Guerrant W, Oyelere AK. Macrocyclic histone deacetylase inhibitors. Curr Top Med Chem 2010;10(14):1423–1440.
95. Levin JI. Macrocycles in Drug Discovery. Cambridge: Royal Society of Chemistry; 2015. pp. 24–499.
96. Furumai R, Matsuyama A, Kobashi N, Lee KH, Nishiyama N, Nakajima I, Tanaka A, Komatsu Y, Nishino N, Yoshida M, Horinouchi S. FK228 (depsipeptide) as a natural prodrug that inhibits class I histone deacetylases. Cancer Res 2002;62(17):4916–4921.
97. Taori K, Paul VJ, Luesch H. Structure and activity of largazole, a potent antiproliferative agent from the Floridian marine cyanobacterium Symploca sp. J Am Chem Soc 2008;130(6):1806–1807.
98. Ueda H, Nakajima H, Hori Y, Goto T, Okuhara M. Action of Fr901228, a novel antitumor bicyclic depsipeptide produced by chromobacterium-violaceum no-968, on Ha-Ras transformed Nih3t3 cells. Biosci Biotechnol Biochem 1994;58(9):1579–1583.
99. Ueda H, Nakajima H, Hori Y, Fujita T, Nishimura M, Goto T, Okuhara M. Fr901228, a novel antitumor bicyclic depsipeptide produced by chromobacterium-violaceum No-968. 1. Taxonomy, fermentation, isolation, physicochemical and biological properties, and antitumor-activity. J Antibiot (Tokyo) 1994;47(3):301–310.
100. Curtin ML, Garland RB, Heyman HR, Frey RR, Michaelides MR, Li JL, Pease LJ, Glaser KB, Marcotte PA, Davidsen SK. Succinimide hydroxamic acids as potent inhibitors of histone deacetylase (HDAC). Bioorg Med Chem Lett 2002;12(20):2919–2923.
101. Pirali T, Faccio V, Mossetti R, Grolla AA, Di Micco S, Bifulco G, Genazzani AA, Tron GC. Synthesis, molecular docking and biological evaluation as HDAC inhibitors of cyclopeptide mimetics by a tandem three-component reaction and intramolecular [3+2] cycloaddition. Mol Divers 2010;14(1):109–121.
102. Chen PC, Patil V, Guerrant W, Green P, Oyelere AK. Synthesis and structure-activity relationship of histone deacetylase (HDAC) inhibitors with triazole-linked cap group. Bioorg Med Chem 2008;16(9):4839–4853.
103. Mwakwari SC, Guerrant W, Patil V, Khan SI, Tekwani BL, Gurard-Levin ZA, Mrksich M, Oyelere AK. Non-peptide macrocyclic histone deacetylase inhibitors derived from tricyclic ketolide skeleton. J Med Chem 2010;53(16):6100–6111.
104. Li XH, Huang ML, Wang SM, Wang Q. Selective inhibition of bicyclic tetrapeptide histone deacetylase inhibitor on HDAC4 and K562 leukemia cell. Asian Pac J Cancer Prev 2013;14(12):7095–7100.
105. Rajak H, Singh A, Dewangan PK, Patel V, Jain DK, Tiwari SK, Veerasamy R, Sharma PC. Peptide based macrocycles: Selective histone deacetylase inhibitors with antiproliferative activity. Curr Med Chem 2013;20(14):1887–1903.
106. Shindoh N, Mori M, Terada Y, Oda K, Amino N, Kita A, Taniguchi M, Sohda KY, Nagai K, Sowa Y, Masuoka Y, Orita M, Sasamata M, Matsushime H, Furuichi K, Sakai T. YM753, a novel histone deacetylase inhibitor, exhibits antitumor activity with selective, sustained accumulation of acetylated histones in tumors in the WiDr xenograft model. Int J Oncol 2008;32(3):545–555.
107. Kijima M, Yoshida M, Sugita K, Horinouchi S, Beppu T. Trapoxin, an antitumor cyclic tetrapeptide, is an irreversible inhibitor of mammalian histone deacetylase. J Biol Chem 1993;268(30):22429–22435.
108. Bauden M, Tassidis H, Ansari D. In vitro cytotoxicity evaluation of HDAC inhibitor Apicidin in pancreatic carcinoma cells subsequent time and dose dependent treatment. Toxicol Lett 2015;236(1):8–15.
109. Wen SJ, Carey KL, Nakao Y, Fusetani N, Packham G, Ganesan A. Total synthesis of azumamide A and azumamide E, evaluation as histone deacetylase inhibitors, and design of a more potent analogue. Org Lett 2007;9(6):1105–1108.
110. Tan HWS, Sim AYL, Huang SL, Leng Y, Long YC. HC toxin (a HDAC inhibitor) enhances IRS1-Akt signalling and metabolism in mouse myotubes. J Mol Endocrinol 2015;55(3):197–207.
111. Huang D, Li X, Sun L, Xiu Z, Nishino N. Synthesis, evaluation and molecular modeling of cyclic tetrapeptide histone deacetylase inhibitors as anticancer agents. J Pept Sci 2012;18(4):242–251.
112. Kim B, Park H, Salvador LA, Serrano PE, Kwan JC, Zeller SL, Chen Q-Y, Ryu S, Liu Y, Byeon S, Luesch H, Hong J. Evaluation of class I HDAC isoform selectivity of largazole analogues. Bioorg Med Chem Lett 2014;24(16):3728–3731.
113. Ni MH, Esposito E, Raj VP, Muzi L, Zunino F, Zuco V, Cominetti D, Penco S, Dal Pozzo A. New macrocyclic analogs of the natural histone deacetylase inhibitor FK228; design, synthesis and preliminary biological evaluation. Bioorg Med Chem 2015;23(21):6785–6793.
114. Wang C, Flemming CJ, Cheng YQ. Discovery and activity profiling of thailandepsins A through F, potent histone deacetylase inhibitors, from Burkholderia thailandensis E264. Medchemcomm 2012;3(8):976–981.
115. Wang C, Henkes LM, Doughty LB, He M, Wang D, Meyer-Almes FJ, Cheng YQ. Thailandepsins: Bacterial products with potent histone deacetylase inhibitory activities and broad-spectrum antiproliferative activities. J Nat Prod 2011;74(10):2031–2038.
116. Yao YW, Tu ZC, Liao CZ, Wang Z, Li S, Yao HQ, Li Z, Jiang S. Discovery of novel class I histone deacetylase inhibitors with promising in vitro and in vivo antitumor activities. J Med Chem 2015;58(19):7672–7680.
117. Li XL, Tu ZC, Li H, Liu CP, Li Z, Sun Q, Yao YW, Liu JS, Jiang S. Biological evaluation of new largazole analogues: Alteration of macrocyclic scaffold with click chemistry. ACS Med Chem Lett 2013;4(1):132–136.
118. Bressi JC, Jennings AJ, Skene R, Wu Y, Melkus R, De Jong R, O'Connell S, Grimshaw CE, Navre M, Gangloff AR. Exploration of the HDAC2 foot pocket: Synthesis and SAR of substituted N-(2-aminophenyl)benzamides. Bioorg Med Chem Lett 2010;20(10):3142–3145.
119. Schuetz A, Min J, Allali-Hassani A, Schapira M, Shuen M, Loppnau P, Mazitschek R, Kwiatkowski NP, Lewis TA, Maglathin RL, McLean TH, Bochkarev A, Plotnikov AN, Vedadi M, Arrowsmith CH. Human HDAC7 harbors a class IIa histone deacetylase-specific zinc binding motif and cryptic deacetylase activity. J Biol Chem 2008;283(17):11355–11363.
120. Fukui Y, Narita K, Dan S, Yamori T, Ito A, Yoshida M, Katoh T. Total synthesis of burkholdacs A and B and 5,6,20-tri-epi-burkholdac A: HDAC inhibition and antiproliferative activity. Eur J Med Chem 2014;76:301–313.
121. Hoque MA, Islam MN, Islam MS, Kato T, Nishino N, Ito A, Yoshida M. Design and synthesis of CHAP31, trapoxin B and HC-toxin based bicyclic tetrapeptides disulfide as potent histone deacetylase inhibitors. Bioorg Med Chem 2014;22(15):3850–3855.
122. Islam MN, Islam MS, Hoque MA, Kato T, Nishino N, Ito A, Yoshida M. Bicyclic tetrapeptide histone deacetylase inhibitors with methoxymethyl ketone and boronic acid zinc-binding groups. Bioorg Chem 2014;57:121–126.
123. Islam MN, Islam MS, Hoque MA, Kato T, Nishino N, Ito A, Yoshida M. Bicyclic tetrapeptides as potent HDAC inhibitors: effect of aliphatic loop position and hydrophobicity on inhibitory activity. Bioorg Med Chem 2014;22(15):3862–3870.
124. Ko KS, Steffey ME, Brandvold KR, Soellner MB. Development of a chimeric c-Src kinase and HDAC inhibitor. ACS Med Chem Lett 2013;4(8):779–783.
125. Kostyniuk CL, Dehm SM, Batten D, Bonham K. The ubiquitous and tissue specific promoters of the human SRC gene are repressed by inhibitors of histone deacetylases. Oncogene 2002;21(41):6340–6347.
126. Atadja P. Development of the pan-DAC inhibitor panobinostat (LBH589): Successes and challenges. Cancer Lett 2009;280(2):233–241.
127. Cai X, Zhai HX, Wang J, Forrester J, Qu H, Yin L, Lai CJ, Bao RD, Qian CG. Discovery of 7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide (CUDC-101) as a potent multi-acting HDAC, EGFR, and HER2 inhibitor for the treatment of cancer. J Med Chem 2010;53(5):2000–2009.
128. Galloway TJ, Wirth LJ, Colevas AD, Gilbert J, Bauman JE, Saba NF, Raben D, Mehra R, Ma AW, Atoyan R, Wang J, Burtness B, Jimeno A. A phase I study of CUDC-101, a multitarget inhibitor of HDACs, EGFR, and HER2, in combination with chemoradiation in patients with head and neck squamous cell carcinoma. Clin Cancer Res 2015;21(7):1566–1573.
129. Shimizu T, LoRusso PM, Papadopoulos KP, Patnaik A, Beeram M, Smith LS, Rasco DW, Mays TA, Chambers G, Ma A, Wang J, Laliberte R, Voi M, Tolcher AW. Phase I first-in-human study of CUDC-101, a multitargeted inhibitor of HDACs, EGFR, and HER2 in patients with advanced solid tumors. Clin Cancer Res 2014;20(19):5032–5040.
130. Qian CG, Lai CJ, Bao RD, Wang DG, Wang J, Xu GX, Atoyan R, Qu H, Yin L, Samson M, Zifcak B, Ma AWS, DellaRocca S, Borek M, Zhai HX, Cai X, Voi M. Cancer network disruption by a single molecule inhibitor targeting both histone deacetylase activity and phosphatidylinositol 3-kinase signaling. Clin Cancer Res 2012;18(15):4104–4113.
131. Szyk A, Deaconescu AM, Spector J, Goodman B, Valenstein ML, Ziolkowska NE, Kormendi V, Grigorieff N, Roll-Mecak A. Molecular basis for age-dependent microtubule acetylation by tubulin acetyltransferase. Cell 2014;157(6):1405–1415.
132. Hai Y, Christianson DW. Histone deacetylase 6 structure and molecular basis of catalysis and inhibition. Nat Chem Biol 2016;12(9):741–747.
133. Liu YL, Li L, Min JR. Structural biology HDAC6 finally crystal clear. Nat Chem Biol 2016;12(9):660–661.
134. Miyake Y, Keusch JJ, Wang L, Saito M, Hess D, Wang X, Melancon BJ, Helquist P, Gut H, Matthias P. Structural insights into HDAC6 tubulin deacetylation and its selective inhibition. Nat Chem Biol 2016;12(9):748–754.
135. Dallavalle S, Pisano C, Zunino F. Development and therapeutic impact of HDAC6-selective inhibitors. Biochem Pharmacol 2012;84(6):756–765.
136. Santo L, Hideshima T, Kung AL, Tseng JC, Tamang D, Yang M, Jarpe M, van Duzer JH, Mazitschek R, Ogier WC, Cirstea D, Rodig S, Eda H, Scullen T, Canavese M, Bradner J, Anderson KC, Jones SS, Raje N. Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma. Blood 2012;119(11):2579–2589.
137. Mithraprabhu S, Khong T, Jones SS, Spencer A. Histone deacetylase (HDAC) inhibitors as single agents induce multiple myeloma cell death principally through the inhibition of class I HDAC. Br J Haematol 2013;162(4):559–562.
138. Bergman JA, Woan K, Perez-Villarroel P, Villagra A, Sotomayor EM, Kozikowski AP. Selective histone deacetylase 6 inhibitors bearing substituted urea linkers inhibit melanoma cell growth. J Med Chem 2012;55(22):9891–9899.
139. 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(2):639–651.
140. Wagner FF, Olson DE, Gale JP, Kaya T, Weiwer M, Aidoud N, Thomas M, Davoine EL, Lemercier BC, Zhang YL, Holson EB. Potent and selective inhibition of histone deacetylase 6 (HDAC6) does not require a surface-binding motif. J Med Chem 2013;56(4):1772–1776.
141. Butler KV, Kalin J, Brochier C, Vistoli G, Langley B, Kozikowski AP. Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A. J Am Chem Soc 2010;132(31):10842–10846.
142. Smil DV, Manku S, Chantigny YA, Leit S, Wahhab A, Yan TP, Fournel M, Maroun C, Li ZM, Lemieux AM, Nicolescu A, Rahil J, Lefebvre S, Panetta A, Besterman JM, Deziel R. Novel HDAC6 isoform selective chiral small molecule histone deacetylase inhibitors. Bioorg Med Chem Lett 2009;19(3):688–692.
143. 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(10):2874–2878.
144. Yanuar A, Azminah EY, Andika EY, Erlina L, Syahdi RR. In silico approach to finding new active compounds from histone deacetylase (HDAC) family. Curr Pharm Des 2016;22(23):3488–3497.
145. Krishna S, Kumar V, Siddiqi MI. Recent advances in computer-assisted structure-based identification and design of histone deacetylases inhibitors. Curr Top Med Chem 2016;16(9):934–947.
146. Sadri-Vakili G, Cha JH. Histone deacetylase inhibitors: A novel therapeutic approach to Huntington's disease (complex mechanism of neuronal death). Curr Alzheimer Res 2006;3(4):403–408.
147. Marek M, Kannan S, Hauser AT, Moraes Mourao M, Caby S, Cura V, Stolfa DA, Schmidtkunz K, Lancelot J, Andrade L, Renaud JP, Oliveira G, Sippl W, Jung M, Cavarelli J, Pierce RJ, Romier C. Structural basis for the inhibition of histone deacetylase 8 (HDAC8), a key epigenetic player in the blood fluke Schistosoma mansoni. PLoS Pathog 2013;9(9):e1003645.
148. Bertrand P. Inside HDAC with HDAC inhibitors. Eur J Med Chem 2010;45(6):2095–2116.
149. Roche J, Bertrand P. Inside HDACs with more selective HDAC inhibitors. Eur J Med Chem 2016;121:451–483.
150. Suzuki T, Nagano Y, Kouketsu A, Matsuura A, Maruyama S, Kurotaki M, Nakagawa H, Miyata N. Novel inhibitors of human histone deacetylases: Design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates. J Med Chem 2005;48(4):1019–1032.
151. Gong WJ, Wu RB, Zhang YK. Thiol versus hydroxamate as zinc binding group in HDAC inhibition: An ab initio QM/MM molecular dynamics study. J Comput Chem 2015;36(30):2228–2235.
152. Kinzel O, Llauger-Bufi L, Pescatore G, Rowley M, Schultz-Fademrecht C, Monteagudo E, Fonsi M, Paz OG, Fiore F, Steinkuhler C, Jones P. Discovery of a potent class I selective ketone histone deacetylase inhibitor with antitumor activity in vivo and optimized pharmacokinetic properties. J Med Chem 2009;52(11):3453–3456.
153. Suzuki N, Suzuki T, Ota Y, Nakano T, Kurihara M, Okuda H, Yamori T, Tsumoto H, Nakagawa H, Miyata N. Design, synthesis, and biological activity of boronic acid-based histone deacetylase inhibitors. J Med Chem 2009;52(9):2909–2922.
154. Jose B, Oniki Y, Kato T, Nishino N, Sumida Y, Yoshida M. Novel histone deacetylase inhibitors: Cyclic tetrapeptide with trifluoromethyl and pentafluoroethyl ketones. Bioorg Med Chem Lett 2004;14(21):5343–5346.
155. Li Y, Woster PM. Discovery of a new class of histone deacetylase inhibitors with a novel zinc binding group. Medchemcomm 2015;6(4):613–618.
156. Liu XH, Song HY, Zhang JX, Han BC, Wei XN, Ma XH, Cui WK, Chen YZ. Identifying novel type ZBGs and nonhydroxamate HDAC inhibitors through a SVM based virtual screening approach. Mol Inform 2010;29(5):407–420.
157. Charrier C, Roche J, Gesson JP, Bertrand P. Antiproliferative activities of a library of hybrids between indanones and HDAC inhibitor SAHA and MS-275 analogues. Bioorg Med Chem Lett 2007;17(22):6142–6146.
158. Siliphaivanh P, Harrington P, Witter DJ, Otte K, Tempest P, Kattar S, Kral AM, Fleming JC, Deshmukh SV, Harsch A, Secrist PJ, Miller TA. Design of novel histone deacetylase inhibitors. Bioorg Med Chem Lett 2007;17(16):4619–4624.
159. Estiu G, Greenberg E, Harrison CB, Kwiatkowski NP, Mazitschek R, Bradner JE, Wiest O. Structural origin of selectivity in class II-selective histone deacetylase inhibitors. J Med Chem 2008;51(10):2898–2906.
160. 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 USA 2003;100(8):4389–4394.
161. Zou H, Wu YQ, Navre M, Sang BC. Characterization of the two catalytic domains in histone deacetylase 6. Biochem Biophys Res Commun 2006;341(1):45–50.
162. Guo YS, Xiao JF, Guo ZR, Chu FM, Cheng YG, Wu S. Exploration of a binding mode of indole amide analogues as potent histone deacetylase inhibitors and 3D-QSAR analyses. Bioorg Med Chem 2005;13(18):5424–5434.
163. Juvale DC, Kulkarni VV, Deokar HS, Wagh NK, Padhye SB, Kulkarni VM. 3D-QSAR of histone deacetylase inhibitors: hydroxamate analogues. Org Biomol Chem 2006;4(15):2858–2868.
164. Katritzky AR, Slavov SH, Dobchev DA, Karelson M. Comparison between 2D and 3D-QSAR approaches to correlate inhibitor activity for a series of indole amide hydroxamic acids. QSAR Comb Sci 2007;26(3):333–345.
165. Wagh NK, Deokar HS, Juvale DC, Kadam SS, Kulkarni VM. 3D-QSAR of histone deacetylase inhibitors as anticancer agents by genetic function approximation. Indian J Biochem Biophys 2006;43(6):360–371.
166. Ragno R, Simeoni S, Valente S, Massa S, Mai A. 3-D QSAR studies on histone deacetylase inhibitors. A GOLPE/GRID approach on different series of compounds. J Chem Inf Model 2006;46(3):1420–1430.
167. Wang DF, Wiest O, Helquist P, Lan-Hargest HY, Wiech NL. QSAR studies of PC-3 cell line inhibition activity of TSA and SAHA-like hydroxamic acids. Bioorg Med Chem Lett 2004;14(3):707–711.
168. Tang H, Wang XS, Huang XP, Roth BL, Butler KV, Kozikowski AP, Jung M, Tropsha A. Novel inhibitors of human histone deacetylase (HDAC) identified by QSAR modeling of known inhibitors, virtual screening, and experimental validation. J Chem Inf Model 2009;49(2):461–476.
169. Chen YD, Jiang YJ, Zhou JW, Yu QS, You QD. Identification of ligand features essential for HDACs inhibitors by pharmacophore modeling. J Mol Graph Model 2008;26(7):1160–1168.
170. Silvestri L, Ballante F, Mai A, Marshall GR, Ragno R. Histone deacetylase inhibitors: Structure-based modeling and isoform-selectivity prediction. J Chem Inf Model 2012;52(8):2215–2235.
171. Micelli C, Rastelli G. Histone deacetylases: Structural determinants of inhibitor selectivity. Drug Discov Today 2015;20(6):718–735.
172. Wang DF. Computational studies on the histone deacetylases and the design of selective histone deacetylase inhibitors. Curr Top Med Chem 2009;9(3):241–256.
173. Deschamps N, Simoes-Pires CA, Carrupt PA, Nurisso A. How the flexibility of human histone deacetylases influences ligand binding: An overview. Drug Discov Today 2015;20(6):736–742.
174. Huang YX, Zhao J, Song QH, Zheng LH, Fan C, Liu TT, Bao YL, Sun LG, Zhang LB, Li YX. Virtual screening and experimental validation of novel histone deacetylase inhibitors. BMC Pharmacol Toxicol 2016;17(1):32.
175. Martinez-Ramos F, Luna-Palencia GR, Vasquez-Moctezuma I, Mendez-Luna D, Fragoso-Vazquez MJ, Trujillo-Ferrara J, Meraz-Rios MA, Mendieta-Wejebe JE, Correa-Basurto J. Docking studies of glutamine valproic acid derivative (S)-5-amino-2-(heptan-4-ylamino)-5-oxopentanoic acid (Gln-VPA) on HDAC8 with biological evaluation in HeLa cells. Anticancer Agents Med Chem 2016;16(11):1485–1490.
176. Padmanabhan B, Ramu M, Mathur S, Unni S, Thiyagarajan S. Identification of new inhibitors for human SIRT1: An in-silico approach. Med Chem 2016;12(4):347–361.
177. Mohseni J, Al-Najjar BO, Wahab HA, Zabidi-Hussin ZA, Sasongko TH. Transcript, methylation and molecular docking analyses of the effects of HDAC inhibitors, SAHA and Dacinostat, on SMN2 expression in fibroblasts of SMA patients. J Hum Genet 2016;61(9):823–830.
178. Sixto-Lopez Y, Gomez-Vidal JA, Correa-Basurto J. Exploring the potential binding sites of some known HDAC inhibitors on some HDAC8 conformers by docking studies. Appl Biochem Biotechnol 2014;173(7):1907–1926.
179. Melesina J, Robaa D, Pierce RJ, Romier C, Sippl W. Homology modeling of parasite histone deacetylases to guide the structure-based design of selective inhibitors. J Mol Graph Model 2015;62:342–361.
180. Singh R, Singh S, Pandey PN. In-silico analysis of Sirt2 from Schistosoma mansoni: Structures, conformations, and interactions with inhibitors. J Biomol Struct Dyn 2016;34(5):1042–1051.
181. Kalyaanamoorthy S, Chen YP. Exploring inhibitor release pathways in histone deacetylases using random acceleration molecular dynamics simulations. J Chem Inf Model 2012;52(2):589–603.
182. Zhou J, Li M, Chen N, Wang S, Luo HB, Zhang Y, Wu R. Computational design of a time-dependent histone deacetylase 2 selective inhibitor. ACS Chem Biol 2015;10(3):687–692.
183. Singh R, Pandey PN. Molecular docking and molecular dynamics study on SmHDAC1 to identify potential lead compounds against schistosomiasis. Mol Biol Rep 2015;42(3):689–698.
184. Noor Z, Afzal N, Rashid S. Exploration of novel inhibitors for class I histone deacetylase isoforms by QSAR modeling and molecular dynamics simulation assays. PLoS One 2015;10(10):1–23.
185. Ganai SA, Shanmugam K, Mahadevan V. Energy-optimised pharmacophore approach to identify potential hotspots during inhibition of Class II HDAC isoforms. J Biomol Struct Dyn 2015;33(2):374–387.
186. Kalyaanamoorthy S, Chen YP. Energy based pharmacophore mapping of HDAC inhibitors against class I HDAC enzymes. Biochim Biophys Acta 2013;1834(1):317–328.
187. Maolanon AR, Madsen AS, Olsen CA. Innovative strategies for selective inhibition of histone deacetylases. Cell Chem Biol 2016;23(7):759–768.
188. Ma N, Luo Y, Wang Y, Liao C, Ye WC, Jiang S. Selective histone deacetylase inhibitors with anticancer activity. Curr Top Med Chem 2016;16(4):415–426.
189. Ganai SA, Ramadoss M, Mahadevan V. Histone deacetylase (HDAC) inhibitors – Emerging roles in neuronal memory, learning, synaptic plasticity and neural regeneration. Curr Neuropharmacol 2016;14(1):55–71.
190. Peedicayil J. Epigenetic drugs for multiple sclerosis. Curr Neuropharmacol 2016;14(1):3–9.
191. Yoon S, Eom GH. HDAC and HDAC inhibitor: From cancer to cardiovascular diseases. Chonnam Med J 2016;52(1):1–11.
192. Wang W, Cui SS, Lu R, Zhang H. Is there any therapeutic value for the use of histone deacetylase inhibitors for chronic pain? Brain Res Bull 2016;125:44–52.
193. Fuchikami M, Yamamoto S, Morinobu S, Okada S, Yamawaki Y, Yamawaki S. The potential use of histone deacetylase inhibitors in the treatment of depression. Prog Neuro-Psychopharmacol Biol Psychiatry 2016;64:320–324.
194. Kelly WK, Richon VM, O'Connor O, Curley T, MacGregor-Curtelli B, Tong W, Klang M, Schwartz L, Richardson S, Rosa E, Drobnjak M, Cordon-Cordo C, Chiao JH, Rifkind R, Marks PA, Scher H. Phase I clinical trial of histone deacetylase inhibitor: Suberoylanilide hydroxamic acid administered intravenously. Clin Cancer Res 2003;9(10):3578–3588.
195. Galli M, Salmoiraghi S, Golay J, Gozzini A, Crippa C, Pescosta N, Rambaldi A. A phase II multiple dose clinical trial of histone deacetylase inhibitor ITF2357 in patients with relapsed or progressive multiple myeloma. Ann Hematol 2010;89(2):185–190.
196. Mottamal M, Zheng SL, Huang TL, Wang GD. Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents. Molecules 2015;20(3):3898–3941.