Discovery of the first histone deacetylase 6/8 dual inhibitors

Journal of Medicinal Chemistry

Volumn 56, Issue 11, 2013, Pages 4816-4820

  Olson, David E ^a   Wagner, Florence F ^a   Kaya, Taner ^a   Gale, Jennifer P ^a   Aidoud, Nadia ^a   Davoine, Emeline L ^a   Lazzaro, Fanny ^a   Weïwer, Michel ^a   Zhang, Yan Ling ^a   Holson, Edward B ^a  

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

Author keywords

[No Author keywords available]

Indexed keywords

HISTONE DEACETYLASE 6; HISTONE DEACETYLASE 8; HYDROXAMIC ACID;

ARTICLE; CRYSTAL STRUCTURE; HUMAN; MOLECULAR DOCKING; PHYLOGENY;

ANTINEOPLASTIC AGENTS; HELA CELLS; HISTONE DEACETYLASE INHIBITORS; HISTONE DEACETYLASES; HUMANS; HYDROXAMIC ACIDS; MOLECULAR DOCKING SIMULATION; PHTHALIC ACIDS; PROTEIN BINDING; REPRESSOR PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84879048463     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm400390r     Document Type: Article

References (40)

1. Haberland, M.; Montgomery, R. L.; Olson, E. N. The many roles of histone deacetylases in development and physiology: implications for disease and therapy Nature Rev. Genet. 2009, 10, 32-42
2. Fass, D. M.; Kemp, M. M.; Schroeder, F. A.; Wagner, F. F.; Wang, Q.; Holson, E. B. Histone acetylation and deacetylation. In Epigenetic Regulation and Epigenomics: Advances in Molecular Biology and Medicine; Wiley-VCH Verlag & Co. KGaA: Weinheim, Germany, 2012; pp 515-561.
3. Marks, P. A.; Richon, V. M.; Miller, T.; Kelly, W. K. Histone deacetylase inhibitors Adv. Cancer Res. 2004, 91, 137-168 (Pubitemid 39140958)
4. de Ruijter, A. J. M.; Van Gennip, A. H.; Caron, H. N.; Kemp, S.; Van Kuilenburg, A. B. P. Histone deacetylases (HDACs): characterization of the classical HDAC family Biochem. J. 2003, 370, 737-749 (Pubitemid 36399066)
5. Glaser, K. B.; Staver, M. J.; Waring, J. F.; Stender, J.; Ulrich, R. G.; Davidsen, S. K. Gene expression profiling of multiple histone deacetylase (HDAC) inhibitors: defining a common gene set produced by HDAC inhibition in T24 and MDA carcinoma cell lines Mol. Cancer Ther. 2003, 2, 151-163
6. Spange, S.; Wagner, T.; Heinzel, T.; Krämer, O. H. Acetylation of non-histone proteins modulates cellular signalling at multiple levels Int. J. Biochem. Cell Biol. 2009, 41, 185-198
7. Park, S. Y.; Jun, J. A.; Jeong, K. J.; Heo, H. J.; Sohn, J. S.; Lee, H. Y.; Park, C. G.; Kang, J. Histone deacetylases 1, 6 and 8 are critical for invasion in breast cancer Oncol. Rep. 2011, 25, 1677-1681
8. Acharya, M. R.; Sparreboom, A.; Venitz, J.; Figg, W. D. Rational development of histone deacetylase inhibitors as anticancer agents: a review Mol. Pharmacol. 2005, 68, 917-932 (Pubitemid 41345783)
9. Gray, S. G. Epigenetic treatment of neurological disease Epigenomics 2011, 3, 431-450
10. Graff, J.; Tsai, L.-H. The potential of HDAC inhibitors as cognitive enhancers Annu. Rev. Pharmacol. Toxicol. 2013, 53, 311-330
11. Gluckman, P. D.; Hanson, M. A.; Buklijas, T.; Low, F. M.; Beedle, A. S. Epigenetic mechanisms that underpin metabolic and cardiovascular diseases Nature Rev. Endocrinol. 2009, 5, 401-408
12. Mihaylova, M. M.; Vasquez, D. S.; Ravnskjaer, K.; Denechaud, P.-D.; Yu, R. T.; Alvarez, J. G.; Downes, M.; Evans, R. M.; Montminy, M.; Shaw, R. J. Class IIa histone deacetylases are hormone-activated regulators of FOXO and mammalian glucose homeostasis Cell 2011, 145, 607-621
13. Rotilli, D.; Simonetti, G.; Savarino, A.; Palamara, A. T.; Migliaccio, A. R.; Mai, A. Non-cancer uses of histone deacetylase inhibitors: effects on infectious diseases and beta-hemoglobinopathies Curr. Top. Med. Chem. 2009, 9, 272-291
14. Andrews, K. T.; Haque, A.; Jones, M. K. HDAC Inhibitors in Parasitic Diseases Immunol. Cell Biol. 2012, 90, 66-77
15. Gregoretti, I. V.; Lee, Y.-M.; Goodson, H. V. Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis J. Mol. Biol. 2004, 338, 17-31 (Pubitemid 38429783)
16. Fraczek, J.; Vanhaecke, T.; Rogiers, V. Toxicological and metabolic considerations for histone deacetylase inhibitors Expert Opin. Drug Metab. Toxicol. 2013, 9, 441-457
17. Wilting, R. H.; Yanover, E.; Heideman, M. R.; Jacobs, H.; Horner, J.; van der Torre, J.; DePihnho, R. A.; Dannenberg, J.-H. Overlapping functions of HDAC1 and HDAC2 in cell cycle regulation and haematopoiesis EMBO J. 2010, 29, 2586-2597
18. Ononye, S. N.; van Heyst, M.; Falcone, E. M.; Anderson, A. C.; Wright, D. L. Toward isozyme-selective inhibitors of histone deacetylase as therapeutic agents for the treatment of cancer Pharm. Pat. Analyst 2012, 1, 207-221
19. Balasubramanian, S.; Verner, E. V.; Buggy, J. J. Isoform-specific histone deacetylase inhibitors: the next step? Cancer Lett. 2009, 280, 211
20. Bieliauskas, A. V.; Pflum, M. K. H. Isoform-selective histone deacetylase inhibitors Chem. Soc. Rev. 2008, 37, 1402-1413
21. Bradner, J. E.; West, N.; Grachan, M. L.; Greenberg, E. F.; Haggarty, S. J.; Warnow, T.; Mazitschek, R. Chemical phylogenetics of histone deacetylases Nature Chem. Biol. 2010, 6, 238-243
22. Methot, J. L.; Chakravarty, P. K.; Chenard, M.; Close, J.; Cruz, J. C.; Dahlberg, W. K.; Fleming, J.; Hamblett, J. E.; Hamill, J. E.; Harrington, P.; Harsch, A.; Heidebrecht, R.; Hughes, B.; Jung, J.; Kenific, C. M.; Kral, A. M.; Meinke, P. T.; Middleton, R. E.; Ozerova, N.; Sloman, D. L.; Stanton, M. G.; Szewczak, A. A.; Tyagarajan, S.; Witter, D. J.; Secrist, J. P.; Miller, T. A. 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 (Pubitemid 351179353)
23. Moradei, O. M.; Mallais, T. C.; Frechette, S.; Paquin, I.; Tessier, P. E.; Leit, S. M.; Fournel, M.; Bonfils, C.; Trachy-Bourget, M.-C.; Liu, J.; Yan, T. P.; Lu, A.-H.; Rahil, J.; Wang, J.; Lefebvre, S.; Li, Z.; Vaisburg, A. F.; Besterman, J. M. novel aminophenyl benzamide-type histone deacetylase inhibitors with enhanced potency and selectivity J. Med. Chem. 2007, 50, 5543-5546 (Pubitemid 350106005)
24. Butler, K. V.; Kalin, J.; Brochier, C.; Vistoli, G.; Langley, B.; Kozikowski, A. P. Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A J. Am. Chem. Soc. 2010, 132, 10842-10846
25. Balasubramanian, A.; Ramos, J.; Luo, W.; Sirisawad, M.; Verner, E.; Buggy, J. J. A novel histone deacetylase 8 (HDAC8)-specific inhibitor PCI-34051 induces apoptosis in T-cell lymphomas Leukemia 2008, 22, 1026
26. Oehme, I.; Deubzer, H. E.; Wegener, D.; Pickert, D.; Linke, J. P.; Hero, B.; Kopp-Schneider, A.; Westermann, F.; Ulrich, S. M.; von Deimling, A.; Fischer, M.; Witt, O. Histone deacetylase 8 in neuroblastoma tumorigenesis Clin. Cancer Res. 2009, 15, 91-99
27. Lee, J.-Y.; Koga, H.; Kawaguchi, Y.; Tang, W.; Wong, E.; Gao, Y.-S.; Pandey, U. B.; Lu, J.; Taylor, J. P.; Cuervo, A. M.; Yao, T.-P. HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagy EMBO J. 2010, 29, 969-980
28. Namdar, M.; Perez, G.; Ngo, L.; Marks, P. A. Selective inhibition of histone deacetylase 6 (HDAC6) induces DNA damage and sensitizes transformed cells to anticancer agents Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 20003-20008
29. Wagner, F. F.; Olson, D. E.; Gale, J. P.; Kaya, T.; Weïwer, M.; Aidoud, N.; Thomas, M.; Davoine, E. L.; Lemercier, B.; Zhang, Y.-L.; Holson, E. B. Potent and selective inhibition of HDAC6 does not require a surface-binding motif J. Med. Chem. 2013, 56, 1772-1776
30. Galletti, P.; Quintavalla, A.; Ventrici, C.; Giannini, G.; Cabri, W.; Penco, S.; Gallo, G.; Vincenti, S.; Giacomini, D. Azetidinones as zinc-binding groups to design selective HDAC8 inhibitors ChemMedChem. 2009, 4, 1991-2001
31. Kozikowski, A. P.; Tapadar, S.; Luchini, D. N.; Kim, K. H.; Billadeau, D. D. Use of 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
32. We chose to measure inhibition of HDAC8 along with HDACs 2, 4, and 6 as representatives for classes I, IIa, and IIb, respectively. We chose HDACs 2 and 4 due to the availability of crystal structures for these isoforms. Inhibition of HDAC10 and 11 was not measured due to either low purity of the available recombinant HDAC enzyme preparations and/or lack of activity of the enzymes and low substrate conversion. See, Holson, E.; Wagner, F.; Weïwer, M.; Zhang, Y. L.; Haggarty, S. H.; Tsai, L. H. Inhibitors of histone deacetylases. WO2012149540 (A1), Nov 1, 2012.
33. Fernandez-Fuentes, N.; Rai, B. K.; Madrid-Aliste, C. J.; Fajardo, J. E.; Fiser, A. Comparative protein structure modeling by combining multiple templates and optimizing sequence-to-structure alignments Bioinformatics 2007, 23, 2558-2565 http://manaslu.aecom.yu.edu/M4T/
34. Somoza, J. R.; Skene, R. J.; Katz, B. A.; Mol, C.; Ho, J. D.; Jennings, A. J.; Luong, C.; Arvai, A.; Buggy, J. J.; Chi, E.; Tang, J.; Sang, B. C.; Verner, E.; Wynands, R.; Leahy, E. M.; Dougan, D. R.; Snell, G.; Navre, M.; Knuth, M. W.; Swanson, R. V.; McRee, D. E.; Tari, L. W. Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases Structure 2004, 12, 1325-1334 (Pubitemid 38900774)
35. Friesner, R. A.; Banks, J. L.; Murphy, R. B.; Halgren, T. A.; Klicic, J. J.; Mainz, D. T.; Repasky, M. P.; Knoll, E. H.; Shelley, M.; Perry, J. K.; Shaw, D. E.; Francis, P.; Shenkin, P. S. Glide: a new approach for rapid, accurate docking and scoring. 1. method and assessment of docking accuracy J. Med. Chem. 2004, 47, 1739-1749 (Pubitemid 38380917)
36. Estiu, G.; Greenberg, E.; Harrison, C. B.; Kwiatkowski, N. P.; Mazitschek, R.; Bradner, J. E.; Wiest, O. Structural origin of selectivity in class II-selective histone deacetylase inhibitors J. Med. Chem. 2008, 51, 2898-2906 (Pubitemid 351706018)
37. Estiu, G.; West, N.; Mazitschek, R.; Greenberg, E.; Bradner, J. E.; Wiest, O. On the inhibition of histone deacetylase 8 Biorg. Med. Chem. 2010, 18, 4103-4110
38. Suzuki, T.; Ota, Y.; Ri, M.; Bando, M.; Gotoh, A.; Itoh, Y.; Tsumoto, H.; Tatum, P. R.; Mizukami, T.; Nakagawa, H.; Iida, S.; Ueda, R.; Shirahige, K.; Miyata, N. 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
39. Wolfson, N. A.; Pitcairn, C. A.; Fierke, C. A. HDAC8 substrates: histones and beyond Biopolymers 2012, 99, 112-126
40. Hubbert, C.; Guardiola, A.; Shao, R.; Kawaguchi, Y.; Ito, A.; Nixon, A.; Yoshida, M.; Wang, X.-F.; Yao, T.-P. HDAC6 is a microtubule-associated deacetylase Nature 2002, 417, 455-458