KATching-Up on Small Molecule Modulators of Lysine Acetyltransferases

Journal of Medicinal Chemistry

Volumn 59, Issue 4, 2016, Pages 1249-1270

  Simon, Roman P ^a   Robaa, Dina ^b   Alhalabi, Zayan ^b   Sippl, Wolfgang ^b   Jung, Manfred ^a  

^a UNIVERSITY OF FREIBURG   (Germany)

^b MARTIN LUTHER UNIVERSITY HALLE WITTENBERG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ACYLTRANSFERASE; ACYLTRANSFERASE INHIBITOR; LYSINE; LYSINE ACETYLTRANSFERASE; LYSINE ACETYLTRANSFERASE INHIBITOR; LYSINE DEACETYLASE; UNCLASSIFIED DRUG; HISTONE; HISTONE ACETYLTRANSFERASE; HISTONE DEACETYLASE; HISTONE DEACETYLASE INHIBITOR; MOLECULAR LIBRARY;

ARTICLE; DRUG TARGETING; ENZYME STRUCTURE; HISTONE ACETYLATION; HUMAN; NONHUMAN; PROTEIN FAMILY; REACTION ANALYSIS; ACETYLATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DEVELOPMENT; DRUG EFFECTS; GENETIC EPIGENESIS; METABOLISM; MOLECULAR LIBRARY; PHARMACOLOGY;

ACETYLATION; ANIMALS; DRUG DISCOVERY; EPIGENESIS, GENETIC; HISTONE ACETYLTRANSFERASES; HISTONE DEACETYLASE INHIBITORS; HISTONE DEACETYLASES; HISTONES; HUMANS; LYSINE; MODELS, MOLECULAR; SMALL MOLECULE LIBRARIES;

EID: 84959422592     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.5b01502     Document Type: Article

References (175)

1. Zeng, L.; Zhou, M. M. Bromodomain: an acetyl-lysine binding domain FEBS Lett. 2002, 513, 124-128 10.1016/S0014-5793(01)03309-9
2. Kouzarides, T. Chromatin modifications and their function Cell 2007, 128, 693-705 10.1016/j.cell.2007.02.005
3. Smith, B. C.; Denu, J. M. Chemical mechanisms of histone lysine and arginine modifications Biochim. Biophys. Acta, Gene Regul. Mech. 2009, 1789, 45-57 10.1016/j.bbagrm.2008.06.005
4. Marmorstein, R.; Zhou, M. M. Writers and readers of histone acetylation: structure, mechanism, and inhibition Cold Spring Harbor Perspect. Biol. 2014, 6, a018762 10.1101/cshperspect.a018762
5. Sterner, D. E.; Berger, S. L. Acetylation of histones and transcription-related factors Microbiol. Mol. Biol. Rev. 2000, 64, 435-459 10.1128/MMBR.64.2.435-459.2000
6. Choudhary, C.; Kumar, C.; Gnad, F.; Nielsen, M. L.; Rehman, M.; Walther, T. C.; Olsen, J. V.; Mann, M. Lysine acetylation targets protein complexes and co-regulates major cellular functions Science 2009, 325, 834-840 10.1126/science.1175371
7. Kim, S. C.; Sprung, R.; Chen, Y.; Xu, Y.; Ball, H.; Pei, J.; Cheng, T.; Kho, Y.; Xiao, H.; Xiao, L.; Grishin, N. V.; White, M.; Yang, X. J.; Zhao, Y. Substrate and functional diversity of lysine acetylation revealed by a proteomics survey Mol. Cell 2006, 23, 607-618 10.1016/j.molcel.2006.06.026
8. Allis, C. D.; Berger, S. L.; Cote, J.; Dent, S.; Jenuwein, T.; Kouzarides, T.; Pillus, L.; Reinberg, D.; Shi, Y.; Shiekhattar, R.; Shilatifard, A.; Workman, J.; Zhang, Y. New nomenclature for chromatin-modifying enzymes Cell 2007, 131, 633-636 10.1016/j.cell.2007.10.039
9. Mellert, H. S.; McMahon, S. B. Biochemical pathways that regulate acetyltransferase and deacetylase activity in mammalian cells Trends Biochem. Sci. 2009, 34, 571-578 10.1016/j.tibs.2009.06.010
10. Feinberg, A. P. Phenotypic plasticity and the epigenetics of human disease Nature 2007, 447, 433-440 10.1038/nature05919
11. Sun, X. J.; Man, N.; Tan, Y.; Nimer, S. D.; Wang, L. The role of histone acetyltransferases in normal and malignant hematopoiesis Front. Oncol. 2015, 5, 108 10.3389/fonc.2015.00108
12. Schneider, A.; Chatterjee, S.; Bousiges, O.; Selvi, B. R.; Swaminathan, A.; Cassel, R.; Blanc, F.; Kundu, T. K.; Boutillier, A. L. Acetyltransferases (HATs) as targets for neurological therapeutics Neurotherapeutics 2013, 10, 568-588 10.1007/s13311-013-0204-7
13. Wang, Y.; Miao, X.; Liu, Y.; Li, F.; Liu, Q.; Sun, J.; Cai, L. Dysregulation of histone acetyltransferases and deacetylases in cardiovascular diseases Oxid. Med. Cell. Longevity 2014, 2014, 641979 10.1155/2014/641979
14. Caton, P. W.; Nayuni, N. K.; Kieswich, J.; Khan, N. Q.; Yaqoob, M. M.; Corder, R. Metformin suppresses hepatic gluconeogenesis through induction of SIRT1 and GCN5 J. Endocrinol. 2010, 205, 97-106 10.1677/JOE-09-0345
15. Allfrey, V. G.; Faulkner, R.; Mirsky, A. E. Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis Proc. Natl. Acad. Sci. U. S. A. 1964, 51, 786-794 10.1073/pnas.51.5.786
16. Gershey, E. L.; Vidali, G.; Allfrey, V. G. Chemical studies of histone acetylation. The occurrence of epsilon-N-acetyllysine in the f2a1 histone J. Biol. Chem. 1968, 243, 5018-5022
17. Candido, E. P.; Reeves, R.; Davie, J. R. Sodium butyrate inhibits histone deacetylation in cultured cells Cell 1978, 14, 105-113 10.1016/0092-8674(78)90305-7
18. Brownell, J. E.; Allis, C. D. An activity gel assay detects a single, catalytically active histone acetyltransferase subunit in Tetrahymena macronuclei Proc. Natl. Acad. Sci. U. S. A. 1995, 92, 6364-6368 10.1073/pnas.92.14.6364
19. Parthun, M. R.; Widom, J.; Gottschling, D. E. The major cytoplasmic histone acetyltransferase in yeast: links to chromatin replication and histone metabolism Cell 1996, 87, 85-94 10.1016/S0092-8674(00)81325-2
20. Luger, K.; Mader, A. W.; Richmond, R. K.; Sargent, D. F.; Richmond, T. J. Crystal structure of the nucleosome core particle at 2.8 A resolution Nature 1997, 389, 251-260 10.1038/38444
21. Grant, P. A.; Duggan, L.; Cote, J.; Roberts, S. M.; Brownell, J. E.; Candau, R.; Ohba, R.; Owen-Hughes, T.; Allis, C. D.; Winston, F.; Berger, S. L.; Workman, J. L. Yeast Gcn5 functions in two multisubunit complexes to acetylate nucleosomal histones: characterization of an Ada complex and the SAGA (Spt/Ada) complex Genes Dev. 1997, 11, 1640-1650 10.1101/gad.11.13.1640
22. Rojas, J. R.; Trievel, R. C.; Zhou, J.; Mo, Y.; Li, X.; Berger, S. L.; Allis, C. D.; Marmorstein, R. Structure of Tetrahymena GCN5 bound to coenzyme A and a histone H3 peptide Nature 1999, 401, 93-98 10.1038/43487
23. Lau, O. D.; Kundu, T. K.; Soccio, R. E.; Ait-Si-Ali, S.; Khalil, E. M.; Vassilev, A.; Wolffe, A. P.; Nakatani, Y.; Roeder, R. G.; Cole, P. A. HATs off: selective synthetic inhibitors of the histone acetyltransferases p300 and PCAF Mol. Cell 2000, 5, 589-595 10.1016/S1097-2765(00)80452-9
24. Choudhary, C.; Weinert, B. T.; Nishida, Y.; Verdin, E.; Mann, M. The growing landscape of lysine acetylation links metabolism and cell signalling Nat. Rev. Mol. Cell Biol. 2014, 15, 536-550 10.1038/nrm3841
25. Lin, H.; Su, X.; He, B. Protein lysine acylation and cysteine succination by intermediates of energy metabolism ACS Chem. Biol. 2012, 7, 947-960 10.1021/cb3001793
26. Parthun, M. R. Hat1: the emerging cellular roles of a type B histone acetyltransferase Oncogene 2007, 26, 5319-5328 10.1038/sj.onc.1210602
27. Yang, X.; Yu, W.; Shi, L.; Sun, L.; Liang, J.; Yi, X.; Li, Q.; Zhang, Y.; Yang, F.; Han, X.; Zhang, D.; Yang, J.; Yao, Z.; Shang, Y. HAT4, a Golgi apparatus-anchored B-type histone acetyltransferase, acetylates free histone H4 and facilitates chromatin assembly Mol. Cell 2011, 44, 39-50 10.1016/j.molcel.2011.07.032
28. Yang, X. J.; Ogryzko, V. V.; Nishikawa, J.; Howard, B. H.; Nakatani, Y. A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A Nature 1996, 382, 319-324 10.1038/382319a0
29. Wittschieben, B. O.; Otero, G.; de Bizemont, T.; Fellows, J.; Erdjument-Bromage, H.; Ohba, R.; Li, Y.; Allis, C. D.; Tempst, P.; Svejstrup, J. Q. A novel histone acetyltransferase is an integral subunit of elongating RNA polymerase II holoenzyme Mol. Cell 1999, 4, 123-128 10.1016/S1097-2765(00)80194-X
30. Sampath, V.; Liu, B.; Tafrov, S.; Srinivasan, M.; Rieger, R.; Chen, E. I.; Sternglanz, R. Biochemical characterization of Hpa2 and Hpa3, two small closely related acetyltransferases from Saccharomyces cerevisiae J. Biol. Chem. 2013, 288, 21506-21513 10.1074/jbc.M113.486274
31. Lorch, Y.; Beve, J.; Gustafsson, C. M.; Myers, L. C.; Kornberg, R. D. Mediator-nucleosome interaction Mol. Cell 2000, 6, 197-201 10.1016/S1097-2765(05)00007-9
32. Dyda, F.; Klein, D. C.; Hickman, A. B. GCN5-related N-acetyltransferases: a structural overview Annu. Rev. Biophys. Biomol. Struct. 2000, 29, 81-103 10.1146/annurev.biophys.29.1.81
33. Marmorstein, R. Protein modules that manipulate histone tails for chromatin regulation Nat. Rev. Mol. Cell Biol. 2001, 2, 422-432 10.1038/35073047
34. Roth, S. Y.; Denu, J. M.; Allis, C. D. Histone acetyltransferases Annu. Rev. Biochem. 2001, 70, 81-120 10.1146/annurev.biochem.70.1.81
35. Kimura, A.; Matsubara, K.; Horikoshi, M. A decade of histone acetylation: marking eukaryotic chromosomes with specific codes J. Biochem. 2005, 138, 647-662 10.1093/jb/mvi184
36. Dancy, B. M.; Cole, P. A. Protein lysine acetylation by p300/CBP Chem. Rev. 2015, 115, 2419-2452 10.1021/cr500452k
37. Bordoli, L.; Netsch, M.; Luthi, U.; Lutz, W.; Eckner, R. Plant orthologs of p300/CBP: conservation of a core domain in metazoan p300/CBP acetyltransferase-related proteins Nucleic Acids Res. 2001, 29, 589-597 10.1093/nar/29.3.589
38. Borrow, J.; Stanton, V. P., Jr.; Andresen, J. M.; Becher, R.; Behm, F. G.; Chaganti, R. S.; Civin, C. I.; Disteche, C.; Dube, I.; Frischauf, A. M.; Horsman, D.; Mitelman, F.; Volinia, S.; Watmore, A. E.; Housman, D. E. The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein Nat. Genet. 1996, 14, 33-41 10.1038/ng0996-33
39. Neuwald, A. F.; Landsman, D. GCN5-related histone N-acetyltransferases belong to a diverse superfamily that includes the yeast SPT10 protein Trends Biochem. Sci. 1997, 22, 154-155 10.1016/S0968-0004(97)01034-7
40. Reifnyder, C.; Lowell, J.; Clarke, A.; Pillus, L. Yeast SAS silencing genes and human genes associated with AML and HIV-1 Tat interactions are homologous with acetyltransferases Nat. Genet. 1997, 16, 109 10.1038/ng0597-109b
41. Sapountzi, V.; Logan, I. R.; Robson, C. N. Cellular functions of TIP60 Int. J. Biochem. Cell Biol. 2006, 38, 1496-1509 10.1016/j.biocel.2006.03.003
42. Smith, E. R.; Eisen, A.; Gu, W.; Sattah, M.; Pannuti, A.; Zhou, J.; Cook, R. G.; Lucchesi, J. C.; Allis, C. D. ESA1 is a histone acetyltransferase that is essential for growth in yeast Proc. Natl. Acad. Sci. U. S. A. 1998, 95, 3561-3565 10.1073/pnas.95.7.3561
43. Iizuka, M.; Stillman, B. Histone acetyltransferase HBO1 interacts with the ORC1 subunit of the human initiator protein J. Biol. Chem. 1999, 274, 23027-23034 10.1074/jbc.274.33.23027
44. Champagne, N.; Bertos, N. R.; Pelletier, N.; Wang, A. H.; Vezmar, M.; Yang, Y.; Heng, H. H.; Yang, X. J. Identification of a human histone acetyltransferase related to monocytic leukemia zinc finger protein J. Biol. Chem. 1999, 274, 28528-28536 10.1074/jbc.274.40.28528
45. Smith, E. R.; Pannuti, A.; Gu, W.; Steurnagel, A.; Cook, R. G.; Allis, C. D.; Lucchesi, J. C. The drosophila MSL complex acetylates histone H4 at lysine 16, a chromatin modification linked to dosage compensation Mol. Cell. Biol. 2000, 20, 312-318 10.1128/MCB.20.1.312-318.2000
46. Mizzen, C. A.; Yang, X. J.; Kokubo, T.; Brownell, J. E.; Bannister, A. J.; Owen-Hughes, T.; Workman, J.; Wang, L.; Berger, S. L.; Kouzarides, T.; Nakatani, Y.; Allis, C. D. The TAF(II)250 subunit of TFIID has histone acetyltransferase activity Cell 1996, 87, 1261-1270 10.1016/S0092-8674(00)81821-8
47. Hsieh, Y. J.; Kundu, T. K.; Wang, Z.; Kovelman, R.; Roeder, R. G. The TFIIIC90 subunit of TFIIIC interacts with multiple components of the RNA polymerase III machinery and contains a histone-specific acetyltransferase activity Mol. Cell. Biol. 1999, 19, 7697-7704 10.1128/MCB.19.11.7697
48. York, B.; O'Malley, B. W. Steroid receptor coactivator (SRC) family: masters of systems biology J. Biol. Chem. 2010, 285, 38743-38750 10.1074/jbc.R110.193367
49. Spencer, T. E.; Jenster, G.; Burcin, M. M.; Allis, C. D.; Zhou, J.; Mizzen, C. A.; McKenna, N. J.; Onate, S. A.; Tsai, S. Y.; Tsai, M. J.; O'Malley, B. W. Steroid receptor coactivator-1 is a histone acetyltransferase Nature 1997, 389, 194-198 10.1038/38304
50. Doi, M.; Hirayama, J.; Sassone-Corsi, P. Circadian regulator CLOCK is a histone acetyltransferase Cell 2006, 125, 497-508 10.1016/j.cell.2006.03.033
51. Lopes da Rosa, J.; Bajaj, V.; Spoonamore, J.; Kaufman, P. D. A small molecule inhibitor of fungal histone acetyltransferase Rtt109 Bioorg. Med. Chem. Lett. 2013, 23, 2853-2859 10.1016/j.bmcl.2013.03.112
52. Karmodiya, K.; Anamika, K.; Muley, V.; Pradhan, S. J.; Bhide, Y.; Galande, S. Camello, a novel family of Histone Acetyltransferases that acetylate histone H4 and is essential for zebrafish development Sci. Rep. 2014, 4, 6076 10.1038/srep06076
53. Friedmann, D. R.; Aguilar, A.; Fan, J.; Nachury, M. V.; Marmorstein, R. Structure of the alpha-tubulin acetyltransferase, alphaTAT1, and implications for tubulin-specific acetylation Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 19655-19660 10.1073/pnas.1209357109
54. Hou, F.; Zou, H. Two human orthologues of Eco1/Ctf7 acetyltransferases are both required for proper sister-chromatid cohesion Mol. Biol. Cell 2005, 16, 3908-3918 10.1091/mbc.E04-12-1063
55. Portela, A.; Esteller, M. Epigenetic modifications and human disease Nat. Biotechnol. 2010, 28, 1057-1068 10.1038/nbt.1685
56. Selvi, B. R.; Chatterjee, S.; Modak, R.; Eswaramoorthy, M.; Kundu, T. K. Histone acetylation as a therapeutic target Subcell. Biochem. 2013, 61, 567-596 10.1007/978-94-007-4525-4-25
57. Li, Y.; Yang, H. X.; Luo, R. Z.; Zhang, Y.; Li, M.; Wang, X.; Jia, W. H. High expression of p300 has an unfavorable impact on survival in resectable esophageal squamous cell carcinoma Ann. Thorac. Surg. 2011, 91, 1531-1538 10.1016/j.athoracsur.2010.12.012
58. Li, M.; Luo, R. Z.; Chen, J. W.; Cao, Y.; Lu, J. B.; He, J. H.; Wu, Q. L.; Cai, M. Y. High expression of transcriptional coactivator p300 correlates with aggressive features and poor prognosis of hepatocellular carcinoma J. Transl. Med. 2011, 9, 5 10.1186/1479-5876-9-5
59. Bandyopadhyay, D.; Okan, N. A.; Bales, E.; Nascimento, L.; Cole, P. A.; Medrano, E. E. Down-regulation of p300/CBP histone acetyltransferase activates a senescence checkpoint in human melanocytes Cancer Res. 2002, 62, 6231-6239
60. Pattabiraman, D. R.; McGirr, C.; Shakhbazov, K.; Barbier, V.; Krishnan, K.; Mukhopadhyay, P.; Hawthorne, P.; Trezise, A.; Ding, J.; Grimmond, S. M.; Papathanasiou, P.; Alexander, W. S.; Perkins, A. C.; Levesque, J. P.; Winkler, I. G.; Gonda, T. J. Interaction of c-Myb with p300 is required for the induction of acute myeloid leukemia (AML) by human AML oncogenes Blood 2014, 123, 2682-2690 10.1182/blood-2012-02-413187
61. Sun, X. J.; Wang, Z.; Wang, L.; Jiang, Y.; Kost, N.; Soong, T. D.; Chen, W. Y.; Tang, Z.; Nakadai, T.; Elemento, O.; Fischle, W.; Melnick, A.; Patel, D. J.; Nimer, S. D.; Roeder, R. G. A stable transcription factor complex nucleated by oligomeric AML1-ETO controls leukaemogenesis Nature 2013, 500, 93-97 10.1038/nature12287
62. Cereseto, A.; Manganaro, L.; Gutierrez, M. I.; Terreni, M.; Fittipaldi, A.; Lusic, M.; Marcello, A.; Giacca, M. Acetylation of HIV-1 integrase by p300 regulates viral integration EMBO J. 2005, 24, 3070-3081 10.1038/sj.emboj.7600770
63. Deng, L.; de la Fuente, C.; Fu, P.; Wang, L.; Donnelly, R.; Wade, J. D.; Lambert, P.; Li, H.; Lee, C. G.; Kashanchi, F. Acetylation of HIV-1 Tat by CBP/P300 increases transcription of integrated HIV-1 genome and enhances binding to core histones Virology 2000, 277, 278-295 10.1006/viro.2000.0593
64. Chen, S.; Feng, B.; George, B.; Chakrabarti, R.; Chen, M.; Chakrabarti, S. Transcriptional coactivator p300 regulates glucose-induced gene expression in endothelial cells Am. J. Physiol. Endocrinol. Metab. 2010, 298, E127-E137 10.1152/ajpendo.00432.2009
65. Kikuchi, H.; Takami, Y.; Nakayama, T. GCN5: a supervisor in all-inclusive control of vertebrate cell cycle progression through transcription regulation of various cell cycle-related genes Gene 2005, 347, 83-97 10.1016/j.gene.2004.12.007
66. Perez-Luna, M.; Aguasca, M.; Perearnau, A.; Serratosa, J.; Martinez-Balbas, M.; Jesus Pujol, M.; Bachs, O. PCAF regulates the stability of the transcriptional regulator and cyclin-dependent kinase inhibitor p27 Kip1 Nucleic Acids Res. 2012, 40, 6520-6533 10.1093/nar/gks343
67. Shiota, M.; Yokomizo, A.; Tada, Y.; Uchiumi, T.; Inokuchi, J.; Tatsugami, K.; Kuroiwa, K.; Yamamoto, K.; Seki, N.; Naito, S. P300/CBP-associated factor regulates Y-box binding protein-1 expression and promotes cancer cell growth, cancer invasion and drug resistance Cancer Sci. 2010, 101, 1797-1806 10.1111/j.1349-7006.2010.01598.x
68. Toth, M.; Boros, I. M.; Balint, E. Elevated level of lysine 9-acetylated histone H3 at the MDR1 promoter in multidrug-resistant cells Cancer Sci. 2012, 103, 659-669 10.1111/j.1349-7006.2012.02215.x
69. Terreni, M.; Valentini, P.; Liverani, V.; Gutierrez, M. I.; Di Primio, C.; Di Fenza, A.; Tozzini, V.; Allouch, A.; Albanese, A.; Giacca, M.; Cereseto, A. GCN5-dependent acetylation of HIV-1 integrase enhances viral integration Retrovirology 2010, 7, 18 10.1186/1742-4690-7-18
70. Miao, J.; Fan, Q.; Cui, L.; Li, J.; Li, J.; Cui, L. The malaria parasite Plasmodium falciparum histones: organization, expression, and acetylation Gene 2006, 369, 53-65 10.1016/j.gene.2005.10.022
71. Duclot, F.; Meffre, J.; Jacquet, C.; Gongora, C.; Maurice, T. Mice knock out for the histone acetyltransferase p300/CREB binding protein-associated factor develop a resistance to amyloid toxicity Neuroscience 2010, 167, 850-863 10.1016/j.neuroscience.2010.02.055
72. Wei, W.; Coelho, C. M.; Li, X.; Marek, R.; Yan, S.; Anderson, S.; Meyers, D.; Mukherjee, C.; Sbardella, G.; Castellano, S.; Milite, C.; Rotili, D.; Mai, A.; Cole, P. A.; Sah, P.; Kobor, M. S.; Bredy, T. W. p300/CBP-associated factor selectively regulates the extinction of conditioned fear J. Neurosci. 2012, 32, 11930-11941 10.1523/JNEUROSCI.0178-12.2012
73. Colussi, C.; Rosati, J.; Straino, S.; Spallotta, F.; Berni, R.; Stilli, D.; Rossi, S.; Musso, E.; Macchi, E.; Mai, A.; Sbardella, G.; Castellano, S.; Chimenti, C.; Frustaci, A.; Nebbioso, A.; Altucci, L.; Capogrossi, M. C.; Gaetano, C. Nepsilon-lysine acetylation determines dissociation from GAP junctions and lateralization of connexin 43 in normal and dystrophic heart Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 2795-2800 10.1073/pnas.1013124108
74. Sun, C.; Wang, M.; Liu, X.; Luo, L.; Li, K.; Zhang, S.; Wang, Y.; Yang, Y.; Ding, F.; Gu, X. PCAF improves glucose homeostasis by suppressing the gluconeogenic activity of PGC-1alpha Cell Rep. 2014, 9, 2250-2262 10.1016/j.celrep.2014.11.029
75. Kindle, K. B.; Troke, P. J.; Collins, H. M.; Matsuda, S.; Bossi, D.; Bellodi, C.; Kalkhoven, E.; Salomoni, P.; Pelicci, P. G.; Minucci, S.; Heery, D. M. MOZ-TIF2 inhibits transcription by nuclear receptors and p53 by impairment of CBP function Mol. Cell. Biol. 2005, 25, 988-1002 10.1128/MCB.25.3.988-1002.2005
76. Dulak, A. M.; Stojanov, P.; Peng, S.; Lawrence, M. S.; Fox, C.; Stewart, C.; Bandla, S.; Imamura, Y.; Schumacher, S. E.; Shefler, E.; McKenna, A.; Carter, S. L.; Cibulskis, K.; Sivachenko, A.; Saksena, G.; Voet, D.; Ramos, A. H.; Auclair, D.; Thompson, K.; Sougnez, C.; Onofrio, R. C.; Guiducci, C.; Beroukhim, R.; Zhou, Z.; Lin, L.; Lin, J.; Reddy, R.; Chang, A.; Landrenau, R.; Pennathur, A.; Ogino, S.; Luketich, J. D.; Golub, T. R.; Gabriel, S. B.; Lander, E. S.; Beer, D. G.; Godfrey, T. E.; Getz, G.; Bass, A. J. Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity Nat. Genet. 2013, 45, 478-486 10.1038/ng.2591
77. Yang, X. J. MOZ and MORF acetyltransferases: molecular interaction, animal development and human disease Biochim. Biophys. Acta, Mol. Cell Res. 2015, 1853, 1818-1826 10.1016/j.bbamcr.2015.04.014
78. Shiota, M.; Yokomizo, A.; Masubuchi, D.; Tada, Y.; Inokuchi, J.; Eto, M.; Uchiumi, T.; Fujimoto, N.; Naito, S. Tip60 promotes prostate cancer cell proliferation by translocation of androgen receptor into the nucleus Prostate 2010, 70, 540-554 10.1002/pros.21088
79. Ikura, T.; Ogryzko, V. V.; Grigoriev, M.; Groisman, R.; Wang, J.; Horikoshi, M.; Scully, R.; Qin, J.; Nakatani, Y. Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis Cell 2000, 102, 463-473 10.1016/S0092-8674(00)00051-9
80. Iizuka, M.; Takahashi, Y.; Mizzen, C. A.; Cook, R. G.; Fujita, M.; Allis, C. D.; Frierson, H. F., Jr.; Fukusato, T.; Smith, M. M. Histone acetyltransferase Hbo1: catalytic activity, cellular abundance, and links to primary cancers Gene 2009, 436, 108-114 10.1016/j.gene.2009.01.020
81. Dekker, F. J.; van den Bosch, T.; Martin, N. I. Small molecule inhibitors of histone acetyltransferases and deacetylases are potential drugs for inflammatory diseases Drug Discovery Today 2014, 19, 654-660 10.1016/j.drudis.2013.11.012
82. Kuo, M. H.; Allis, C. D. Roles of histone acetyltransferases and deacetylases in gene regulation BioEssays 1998, 20, 615-626 10.1002/(SICI)1521-1878(199808)20:8<615::AID-BIES4>3.0.CO;2-H
83. Lee, K. K.; Workman, J. L. Histone acetyltransferase complexes: one size doesn't fit all Nat. Rev. Mol. Cell Biol. 2007, 8, 284-295 10.1038/nrm2145
84. Schuetz, A.; Bernstein, G.; Dong, A.; Antoshenko, T.; Wu, H.; Loppnau, P.; Bochkarev, A.; Plotnikov, A. N. Crystal structure of a binary complex between human GCN5 histone acetyltransferase domain and acetyl coenzyme A Proteins: Struct., Funct., Genet. 2007, 68, 403-407 10.1002/prot.21407
85. Poux, A. N.; Cebrat, M.; Kim, C. M.; Cole, P. A.; Marmorstein, R. Structure of the GCN5 histone acetyltransferase bound to a bisubstrate inhibitor Proc. Natl. Acad. Sci. U. S. A. 2002, 99, 14065-14070 10.1073/pnas.222373899
86. Poux, A. N.; Marmorstein, R. Molecular basis for Gcn5/PCAF histone acetyltransferase selectivity for histone and nonhistone substrates Biochemistry 2003, 42, 14366-14374 10.1021/bi035632n
87. Clements, A.; Poux, A. N.; Lo, W. S.; Pillus, L.; Berger, S. L.; Marmorstein, R. Structural basis for histone and phosphohistone binding by the GCN5 histone acetyltransferase Mol. Cell 2003, 12, 461-473 10.1016/S1097-2765(03)00288-0
88. Delvecchio, M.; Gaucher, J.; Aguilar-Gurrieri, C.; Ortega, E.; Panne, D. Structure of the p300 catalytic core and implications for chromatin targeting and HAT regulation Nat. Struct. Mol. Biol. 2013, 20, 1040-1046 10.1038/nsmb.2642
89. Liu, X.; Wang, L.; Zhao, K.; Thompson, P. R.; Hwang, Y.; Marmorstein, R.; Cole, P. A. The structural basis of protein acetylation by the p300/CBP transcriptional coactivator Nature 2008, 451, 846-850 10.1038/nature06546
90. Maksimoska, J.; Segura-Pena, D.; Cole, P. A.; Marmorstein, R. Structure of the p300 histone acetyltransferase bound to acetyl-coenzyme A and its analogues Biochemistry 2014, 53, 3415-3422 10.1021/bi500380f
91. Thompson, P. R.; Kurooka, H.; Nakatani, Y.; Cole, P. A. Transcriptional coactivator protein p300. Kinetic characterization of its histone acetyltransferase activity J. Biol. Chem. 2001, 276, 33721-33729 10.1074/jbc.M104736200
92. Thompson, P. R.; Wang, D.; Wang, L.; Fulco, M.; Pediconi, N.; Zhang, D.; An, W.; Ge, Q.; Roeder, R. G.; Wong, J.; Levrero, M.; Sartorelli, V.; Cotter, R. J.; Cole, P. A. Regulation of the p300 HAT domain via a novel activation loop Nat. Struct. Mol. Biol. 2004, 11, 308-315 10.1038/nsmb740
93. Yan, Y.; Barlev, N. A.; Haley, R. H.; Berger, S. L.; Marmorstein, R. Crystal structure of yeast Esa1 suggests a unified mechanism for catalysis and substrate binding by histone acetyltransferases Mol. Cell 2000, 6, 1195-1205 10.1016/S1097-2765(00)00116-7
94. Huang, J.; Wan, B.; Wu, L.; Yang, Y.; Dou, Y.; Lei, M. Structural insight into the regulation of MOF in the male-specific lethal complex and the non-specific lethal complex Cell Res. 2012, 22, 1078-1081 10.1038/cr.2012.72
95. Kadlec, J.; Hallacli, E.; Lipp, M.; Holz, H.; Sanchez-Weatherby, J.; Cusack, S.; Akhtar, A. Structural basis for MOF and MSL3 recruitment into the dosage compensation complex by MSL1 Nat. Struct. Mol. Biol. 2011, 18, 142-149 10.1038/nsmb.1960
96. Sun, B.; Guo, S.; Tang, Q.; Li, C.; Zeng, R.; Xiong, Z.; Zhong, C.; Ding, J. Regulation of the histone acetyltransferase activity of hMOF via autoacetylation of Lys274 Cell Res. 2011, 21, 1262-1266 10.1038/cr.2011.105
97. Yuan, H.; Rossetto, D.; Mellert, H.; Dang, W.; Srinivasan, M.; Johnson, J.; Hodawadekar, S.; Ding, E. C.; Speicher, K.; Abshiru, N.; Perry, R.; Wu, J.; Yang, C.; Zheng, Y. G.; Speicher, D. W.; Thibault, P.; Verreault, A.; Johnson, F. B.; Berger, S. L.; Sternglanz, R.; McMahon, S. B.; Cote, J.; Marmorstein, R. MYST protein acetyltransferase activity requires active site lysine autoacetylation EMBO J. 2012, 31, 58-70 10.1038/emboj.2011.382
98. Li, X.; Wu, L.; Corsa, C. A.; Kunkel, S.; Dou, Y. Two mammalian MOF complexes regulate transcription activation by distinct mechanisms Mol. Cell 2009, 36, 290-301 10.1016/j.molcel.2009.07.031
99. Morales, V.; Straub, T.; Neumann, M. F.; Mengus, G.; Akhtar, A.; Becker, P. B. Functional integration of the histone acetyltransferase MOF into the dosage compensation complex EMBO J. 2004, 23, 2258-2268 10.1038/sj.emboj.7600235
100. Wu, J.; Xie, N.; Wu, Z.; Zhang, Y.; Zheng, Y. G. Bisubstrate inhibitors of the MYST HATs Esa1 and Tip60 Bioorg. Med. Chem. 2009, 17, 1381-1386 10.1016/j.bmc.2008.12.014
101. Kwie, F. H.; Briet, M.; Soupaya, D.; Hoffmann, P.; Maturano, M.; Rodriguez, F.; Blonski, C.; Lherbet, C.; Baudoin-Dehoux, C. New potent bisubstrate inhibitors of histone acetyltransferase p300: design, synthesis and biological evaluation Chem. Biol. Drug Des. 2011, 77, 86-92 10.1111/j.1747-0285.2010.01056.x
102. Cebrat, M.; Kim, C. M.; Thompson, P. R.; Daugherty, M.; Cole, P. A. Synthesis and analysis of potential prodrugs of coenzyme A analogues for the inhibition of the histone acetyltransferase p300 Bioorg. Med. Chem. 2003, 11, 3307-3313 10.1016/S0968-0896(03)00265-7
103. Wadia, J. S.; Dowdy, S. F. Transmembrane delivery of protein and peptide drugs by TAT-mediated transduction in the treatment of cancer Adv. Drug Delivery Rev. 2005, 57, 579-596 10.1016/j.addr.2004.10.005
104. Zheng, Y.; Balasubramanyam, K.; Cebrat, M.; Buck, D.; Guidez, F.; Zelent, A.; Alani, R. M.; Cole, P. A. Synthesis and evaluation of a potent and selective cell-permeable p300 histone acetyltransferase inhibitor J. Am. Chem. Soc. 2005, 127, 17182-17183 10.1021/ja0558544
105. Bandyopadhyay, K.; Baneres, J. L.; Martin, A.; Blonski, C.; Parello, J.; Gjerset, R. A. Spermidinyl-CoA-based HAT inhibitors block DNA repair and provide cancer-specific chemo- and radiosensitization Cell Cycle 2009, 8, 2779-2788 10.4161/cc.8.17.9416
106. Cullis, P. M.; Wolfenden, R.; Cousens, L. S.; Alberts, B. M. Inhibition of histone acetylation by N-[2-(S-coenzyme A)acetyl] spermidine amide, a multisubstrate analog J. Biol. Chem. 1982, 257, 12165-12169
107. Balasubramanyam, K.; Swaminathan, V.; Ranganathan, A.; Kundu, T. K. Small molecule modulators of histone acetyltransferase p300 J. Biol. Chem. 2003, 278, 19134-19140 10.1074/jbc.M301580200
108. Ghizzoni, M.; Wu, J.; Gao, T.; Haisma, H. J.; Dekker, F. J.; George Zheng, Y. 6-alkylsalicylates are selective Tip60 inhibitors and target the acetyl-CoA binding site Eur. J. Med. Chem. 2012, 47, 337-344 10.1016/j.ejmech.2011.11.001
109. Hemshekhar, M.; Sebastin Santhosh, M.; Kemparaju, K.; Girish, K. S. Emerging roles of anacardic acid and its derivatives: a pharmacological overview Basic Clin. Pharmacol. Toxicol. 2012, 110, 122-132 10.1111/j.1742-7843.2011.00833.x
110. Eliseeva, E. D.; Valkov, V.; Jung, M.; Jung, M. O. Characterization of novel inhibitors of histone acetyltransferases Mol. Cancer Ther. 2007, 6, 2391-2398 10.1158/1535-7163.MCT-07-0159
111. Wapenaar, H.; van der Wouden, P. E.; Groves, M. R.; Rotili, D.; Mai, A.; Dekker, F. J. Enzyme kinetics and inhibition of histone acetyltransferase KAT8 Eur. J. Med. Chem. 2015, 105, 289-296 10.1016/j.ejmech.2015.10.016
112. Ghizzoni, M.; Boltjes, A.; Graaf, C.; Haisma, H. J.; Dekker, F. J. Improved inhibition of the histone acetyltransferase PCAF by an anacardic acid derivative Bioorg. Med. Chem. 2010, 18, 5826-5834 10.1016/j.bmc.2010.06.089
113. Chatterjee, S.; Mizar, P.; Cassel, R.; Neidl, R.; Selvi, B. R.; Mohankrishna, D. V.; Vedamurthy, B. M.; Schneider, A.; Bousiges, O.; Mathis, C.; Cassel, J. C.; Eswaramoorthy, M.; Kundu, T. K.; Boutillier, A. L. A novel activator of CBP/p300 acetyltransferases promotes neurogenesis and extends memory duration in adult mice J. Neurosci. 2013, 33, 10698-10712 10.1523/JNEUROSCI.5772-12.2013
114. Sbardella, G.; Castellano, S.; Vicidomini, C.; Rotili, D.; Nebbioso, A.; Miceli, M.; Altucci, L.; Mai, A. Identification of long chain alkylidenemalonates as novel small molecule modulators of histone acetyltransferases Bioorg. Med. Chem. Lett. 2008, 18, 2788-2792 10.1016/j.bmcl.2008.04.017
115. Castellano, S.; Milite, C.; Feoli, A.; Viviano, M.; Mai, A.; Novellino, E.; Tosco, A.; Sbardella, G. Identification of structural features of 2-alkylidene-1,3-dicarbonyl derivatives that induce inhibition and/or activation of histone acetyltransferases KAT3B/p300 and KAT2B/PCAF ChemMedChem 2015, 10, 144-157 10.1002/cmdc.201402371
116. Choi, K. C.; Jung, M. G.; Lee, Y. H.; Yoon, J. C.; Kwon, S. H.; Kang, H. B.; Kim, M. J.; Cha, J. H.; Kim, Y. J.; Jun, W. J.; Lee, J. M.; Yoon, H. G. Epigallocatechin-3-gallate, a histone acetyltransferase inhibitor, inhibits EBV-induced B lymphocyte transformation via suppression of RelA acetylation Cancer Res. 2009, 69, 583-592 10.1158/0008-5472.CAN-08-2442
117. Mai, A.; Cheng, D.; Bedford, M. T.; Valente, S.; Nebbioso, A.; Perrone, A.; Brosch, G.; Sbardella, G.; De Bellis, F.; Miceli, M.; Altucci, L. Epigenetic multiple ligands: mixed histone/protein methyltransferase, acetyltransferase, and class III deacetylase (sirtuin) inhibitors J. Med. Chem. 2008, 51, 2279-2290 10.1021/jm701595q
118. Balasubramanyam, K.; Varier, R. A.; Altaf, M.; Swaminathan, V.; Siddappa, N. B.; Ranga, U.; Kundu, T. K. Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription J. Biol. Chem. 2004, 279, 51163-51171 10.1074/jbc.M409024200
119. Neckers, L.; Trepel, J.; Lee, S.; Chung, E. J.; Lee, M.-J.; Jung, Y.-J.; Marcu, M. G. Curcumin is an inhibitor of p300 histone acetylatransferase Med. Chem. 2006, 2, 169-174 10.2174/157340606776056133
120. Fu, S.; Kurzrock, R. Development of curcumin as an epigenetic agent Cancer 2010, 116, 4670-4676 10.1002/cncr.25414
121. Costi, R.; Di Santo, R.; Artico, M.; Miele, G.; Valentini, P.; Novellino, E.; Cereseto, A. Cinnamoyl compounds as simple molecules that inhibit p300 histone acetyltransferase J. Med. Chem. 2007, 50, 1973-1977 10.1021/jm060943s
122. Arif, M.; Vedamurthy, B. M.; Choudhari, R.; Ostwal, Y. B.; Mantelingu, K.; Kodaganur, G. S.; Kundu, T. K. Nitric oxide-mediated histone hyperacetylation in oral cancer: target for a water-soluble HAT inhibitor, CTK7A Chem. Biol. 2010, 17, 903-913 10.1016/j.chembiol.2010.06.014
123. Ingolfsson, H. I.; Thakur, P.; Herold, K. F.; Hobart, E. A.; Ramsey, N. B.; Periole, X.; de Jong, D. H.; Zwama, M.; Yilmaz, D.; Hall, K.; Maretzky, T.; Hemmings, H. C., Jr.; Blobel, C.; Marrink, S. J.; Kocer, A.; Sack, J. T.; Andersen, O. S. Phytochemicals perturb membranes and promiscuously alter protein function ACS Chem. Biol. 2014, 9, 1788-1798 10.1021/cb500086e
124. Balasubramanyam, K.; Altaf, M.; Varier, R. A.; Swaminathan, V.; Ravindran, A.; Sadhale, P. P.; Kundu, T. K. Polyisoprenylated benzophenone, garcinol, a natural histone acetyltransferase inhibitor, represses chromatin transcription and alters global gene expression J. Biol. Chem. 2004, 279, 33716-33726 10.1074/jbc.M402839200
125. Arif, M.; Pradhan, S. K.; G R, T.; Vedamurthy, B. M.; Agrawal, S.; Dasgupta, D.; Kundu, T. K. Mechanism of p300 specific histone acetyltransferase inhibition by small molecules J. Med. Chem. 2009, 52, 267-277 10.1021/jm800657z
126. Mantelingu, K.; Reddy, B. A.; Swaminathan, V.; Kishore, A. H.; Siddappa, N. B.; Kumar, G. V.; Nagashankar, G.; Natesh, N.; Roy, S.; Sadhale, P. P.; Ranga, U.; Narayana, C.; Kundu, T. K. Specific inhibition of p300-HAT alters global gene expression and represses HIV replication Chem. Biol. 2007, 14, 645-657 10.1016/j.chembiol.2007.04.011
127. Milite, C.; Feoli, A.; Sasaki, K.; La Pietra, V.; Balzano, A. L.; Marinelli, L.; Mai, A.; Novellino, E.; Castellano, S.; Tosco, A.; Sbardella, G. A novel cell-permeable, selective, and noncompetitive inhibitor of KAT3 histone acetyltransferases from a combined molecular pruning/classical isosterism approach J. Med. Chem. 2015, 58, 2779-2798 10.1021/jm5019687
128. Maurer, B.; Rumpf, T.; Scharfe, M.; Stolfa, D. A.; Schmitt, M. L.; He, W.; Verdin, E.; Sippl, W.; Jung, M. Inhibitors of the NAD(+)-dependent protein desuccinylase and demalonylase Sirt5 ACS Med. Chem. Lett. 2012, 3, 1050-1053 10.1021/ml3002709
129. Ravindra, K. C.; Selvi, B. R.; Arif, M.; Reddy, B. A.; Thanuja, G. R.; Agrawal, S.; Pradhan, S. K.; Nagashayana, N.; Dasgupta, D.; Kundu, T. K. Inhibition of lysine acetyltransferase KAT3B/p300 activity by a naturally occurring hydroxynaphthoquinone, plumbagin J. Biol. Chem. 2009, 284, 24453-24464 10.1074/jbc.M109.023861
130. Vasudevarao, M. D.; Mizar, P.; Kumari, S.; Mandal, S.; Siddhanta, S.; Swamy, M. M.; Kaypee, S.; Kodihalli, R. C.; Banerjee, A.; Naryana, C.; Dasgupta, D.; Kundu, T. K. Naphthoquinone-mediated inhibition of lysine acetyltransferase KAT3B/p300, basis for non-toxic inhibitor synthesis J. Biol. Chem. 2014, 289, 7702-7717 10.1074/jbc.M113.486522
131. Modak, R.; Basha, J.; Bharathy, N.; Maity, K.; Mizar, P.; Bhat, A. V.; Vasudevan, M.; Rao, V. K.; Kok, W. K.; Natesh, N.; Taneja, R.; Kundu, T. K. Probing p300/CBP associated factor (PCAF)-dependent pathways with a small molecule inhibitor ACS Chem. Biol. 2013, 8, 1311-1323 10.1021/cb4000597
132. Tohyama, S.; Tomura, A.; Ikeda, N.; Hatano, M.; Odanaka, J.; Kubota, Y.; Umekita, M.; Igarashi, M.; Sawa, R.; Morino, T. Discovery and characterization of NK13650s, naturally occurring p300-selective histone acetyltransferase inhibitors J. Org. Chem. 2012, 77, 9044-9052 10.1021/jo301534b
133. Furumai, R.; Komatsu, Y.; Nishino, N.; Khochbin, S.; Yoshida, M.; Horinouchi, S. 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 10.1073/pnas.98.1.87
134. Stimson, L.; Rowlands, M. G.; Newbatt, Y. M.; Smith, N. F.; Raynaud, F. I.; Rogers, P.; Bavetsias, V.; Gorsuch, S.; Jarman, M.; Bannister, A.; Kouzarides, T.; McDonald, E.; Workman, P.; Aherne, G. W. Isothiazolones as inhibitors of PCAF and p300 histone acetyltransferase activity Mol. Cancer Ther. 2005, 4, 1521-1532 10.1158/1535-7163.MCT-05-0135
135. Furdas, S. D.; Kannan, S.; Sippl, W.; Jung, M. Small molecule inhibitors of histone acetyltransferases as epigenetic tools and drug candidates Arch. Pharm. (Weinheim, Ger.) 2012, 345, 7-21 10.1002/ardp.201100209
136. Furdas, S. D.; Shekfeh, S.; Bissinger, E. M.; Wagner, J. M.; Schlimme, S.; Valkov, V.; Hendzel, M.; Jung, M.; Sippl, W. Synthesis and biological testing of novel pyridoisothiazolones as histone acetyltransferase inhibitors Bioorg. Med. Chem. 2011, 19, 3678-3689 10.1016/j.bmc.2011.01.063
137. Furdas, S. D.; Hoffmann, I.; Robaa, D.; Herquel, B.; Malinka, W.; ͆wiątek, P.; Akhtar, A.; Sippl, W.; Jung, M. Pyrido- and benzisothiazolones as inhibitors of histone acetyltransferases (HATs) MedChemComm 2014, 5, 1856-1862 10.1039/C4MD00245H
138. Carneiro, V. C.; de Abreu da Silva, I. C.; Torres, E. J.; Caby, S.; Lancelot, J.; Vanderstraete, M.; Furdas, S. D.; Jung, M.; Pierce, R. J.; Fantappie, M. R. Epigenetic changes modulate schistosome egg formation and are a novel target for reducing transmission of schistosomiasis PLoS Pathog. 2014, 10, e1004116 10.1371/journal.ppat.1004116
139. Gajer, J. M.; Furdas, S. D.; Grunder, A.; Gothwal, M.; Heinicke, U.; Keller, K.; Colland, F.; Fulda, S.; Pahl, H. L.; Fichtner, I.; Sippl, W.; Jung, M. Histone acetyltransferase inhibitors block neuroblastoma cell growth in vivo Oncogenesis 2015, 4, e137 10.1038/oncsis.2014.51
140. Mai, A.; Rotili, D.; Tarantino, D.; Ornaghi, P.; Tosi, F.; Vicidomini, C.; Sbardella, G.; Nebbioso, A.; Miceli, M.; Altucci, L.; Filetici, P. Small-molecule inhibitors of histone acetyltransferase activity: identification and biological properties J. Med. Chem. 2006, 49, 6897-6907 10.1021/jm060601m
141. Secci, D.; Carradori, S.; Bizzarri, B.; Bolasco, A.; Ballario, P.; Patramani, Z.; Fragapane, P.; Vernarecci, S.; Canzonetta, C.; Filetici, P. Synthesis of a novel series of thiazole-based histone acetyltransferase inhibitors Bioorg. Med. Chem. 2014, 22, 1680-1689 10.1016/j.bmc.2014.01.022
142. Trisciuoglio, D.; Ragazzoni, Y.; Pelosi, A.; Desideri, M.; Carradori, S.; Gabellini, C.; Maresca, G.; Nescatelli, R.; Secci, D.; Bolasco, A.; Bizzarri, B.; Cavaliere, C.; D'Agnano, I.; Filetici, P.; Ricci-Vitiani, L.; Rizzo, M. G.; Del Bufalo, D. CPTH6, a thiazole derivative, induces histone hypoacetylation and apoptosis in human leukemia cells Clin. Cancer Res. 2012, 18, 475-486 10.1158/1078-0432.CCR-11-0579
143. Chimenti, F.; Bizzarri, B.; Maccioni, E.; Secci, D.; Bolasco, A.; Chimenti, P.; Fioravanti, R.; Granese, A.; Carradori, S.; Tosi, F.; Ballario, P.; Vernarecci, S.; Filetici, P. A novel histone acetyltransferase inhibitor modulating Gcn5 network: cyclopentylidene-[4-(4′-chlorophenyl)thiazol-2-yl)hydrazone J. Med. Chem. 2009, 52, 530-536 10.1021/jm800885d
144. Biel, M.; Kretsovali, A.; Karatzali, E.; Papamatheakis, J.; Giannis, A. Design, synthesis, and biological evaluation of a small-molecule inhibitor of the histone acetyltransferase Gcn5 Angew. Chem., Int. Ed. 2004, 43, 3974-3976 10.1002/anie.200453879
145. Bowers, E. M.; Yan, G.; Mukherjee, C.; Orry, A.; Wang, L.; Holbert, M. A.; Crump, N. T.; Hazzalin, C. A.; Liszczak, G.; Yuan, H.; Larocca, C.; Saldanha, S. A.; Abagyan, R.; Sun, Y.; Meyers, D. J.; Marmorstein, R.; Mahadevan, L. C.; Alani, R. M.; Cole, P. A. Virtual ligand screening of the p300/CBP histone acetyltransferase: identification of a selective small molecule inhibitor Chem. Biol. 2010, 17, 471-482 10.1016/j.chembiol.2010.03.006
146. Shrimp, J. H.; Sorum, A. W.; Garlick, J. M.; Guasch, L.; Nicklaus, M. C.; Meier, J. L. Characterizing the Covalent Targets of a Small Molecule Inhibitor of the Lysine Acetyltransferase P300 ACS Med. Chem. Lett. 2015, 10.1021/acsmedchemlett.5b00385
147. Dancy, B. M.; Crump, N. T.; Peterson, D. J.; Mukherjee, C.; Bowers, E. M.; Ahn, Y. H.; Yoshida, M.; Zhang, J.; Mahadevan, L. C.; Meyers, D. J.; Boeke, J. D.; Cole, P. A. Live-cell studies of p300/CBP histone acetyltransferase activity and inhibition ChemBioChem 2012, 13, 2113-2121 10.1002/cbic.201200381
148. Gao, X. N.; Lin, J.; Ning, Q. Y.; Gao, L.; Yao, Y. S.; Zhou, J. H.; Li, Y. H.; Wang, L. L.; Yu, L. A histone acetyltransferase p300 inhibitor C646 induces cell cycle arrest and apoptosis selectively in AML1-ETO-positive AML cells PLoS One 2013, 8, e55481 10.1371/journal.pone.0055481
149. Yang, H.; Pinello, C. E.; Luo, J.; Li, D.; Wang, Y.; Zhao, L. Y.; Jahn, S. C.; Saldanha, S. A.; Planck, J.; Geary, K. R.; Ma, H.; Law, B. K.; Roush, W. R.; Hodder, P.; Liao, D. Small-molecule inhibitors of acetyltransferase p300 identified by high-throughput screening are potent anticancer agents Mol. Cancer Ther. 2013, 12, 610-620 10.1158/1535-7163.MCT-12-0930
150. Wu, J.; Wang, J.; Li, M.; Yang, Y.; Wang, B.; Zheng, Y. G. Small molecule inhibitors of histone acetyltransferase Tip60 Bioorg. Chem. 2011, 39, 53-58 10.1016/j.bioorg.2010.11.003
151. Coffey, K.; Blackburn, T. J.; Cook, S.; Golding, B. T.; Griffin, R. J.; Hardcastle, I. R.; Hewitt, L.; Huberman, K.; McNeill, H. V.; Newell, D. R.; Roche, C.; Ryan-Munden, C. A.; Watson, A.; Robson, C. N. Characterisation of a Tip60 specific inhibitor, NU9056, in prostate cancer PLoS One 2012, 7, e45539 10.1371/journal.pone.0045539
152. Gao, C.; Bourke, E.; Scobie, M.; Famme, M. A.; Koolmeister, T.; Helleday, T.; Eriksson, L. A.; Lowndes, N. F.; Brown, J. A. Rational design and validation of a Tip60 histone acetyltransferase inhibitor Sci. Rep. 2014, 4, 5372 10.1038/srep05372
153. Majmudar, C. Y.; Hojfeldt, J. W.; Arevang, C. J.; Pomerantz, W. C.; Gagnon, J. K.; Schultz, P. J.; Cesa, L. C.; Doss, C. H.; Rowe, S. P.; Vasquez, V.; Tamayo-Castillo, G.; Cierpicki, T.; Brooks, C. L., 3rd; Sherman, D. H.; Mapp, A. K. Sekikaic acid and lobaric acid target a dynamic interface of the coactivator CBP/p300 Angew. Chem., Int. Ed. 2012, 51, 11258-11262 10.1002/anie.201206815
154. Sachchidanand; Resnick-Silverman, L.; Yan, S.; Mutjaba, S.; Liu, W. J.; Zeng, L.; Manfredi, J. J.; Zhou, M. M. Target structure-based discovery of small molecules that block human p53 and CREB binding protein association Chem. Biol. 2006, 13, 81-90 10.1016/j.chembiol.2005.10.014
155. Wang, Q.; Wang, R.; Zhang, B.; Zhang, S.; Zheng, Y.; Wang, Z. Small organic molecules targeting PCAF bromodomain as potent inhibitors of HIV-1 replication MedChemComm 2013, 4, 737-740 10.1039/c3md20376j
156. Borah, J. C.; Mujtaba, S.; Karakikes, I.; Zeng, L.; Muller, M.; Patel, J.; Moshkina, N.; Morohashi, K.; Zhang, W.; Gerona-Navarro, G.; Hajjar, R. J.; Zhou, M. M. A small molecule binding to the coactivator CREB-binding protein blocks apoptosis in cardiomyocytes Chem. Biol. 2011, 18, 531-541 10.1016/j.chembiol.2010.12.021
157. Rooney, T. P.; Filippakopoulos, P.; Fedorov, O.; Picaud, S.; Cortopassi, W. A.; Hay, D. A.; Martin, S.; Tumber, A.; Rogers, C. M.; Philpott, M.; Wang, M.; Thompson, A. L.; Heightman, T. D.; Pryde, D. C.; Cook, A.; Paton, R. S.; Muller, S.; Knapp, S.; Brennan, P. E.; Conway, S. J. A series of potent CREBBP bromodomain ligands reveals an induced-fit pocket stabilized by a cation-pi interaction Angew. Chem., Int. Ed. 2014, 53, 6126-6130 10.1002/anie.201402750
158. Hay, D. A.; Fedorov, O.; Martin, S.; Singleton, D. C.; Tallant, C.; Wells, C.; Picaud, S.; Philpott, M.; Monteiro, O. P.; Rogers, C. M.; Conway, S. J.; Rooney, T. P.; Tumber, A.; Yapp, C.; Filippakopoulos, P.; Bunnage, M. E.; Muller, S.; Knapp, S.; Schofield, C. J.; Brennan, P. E. Discovery and optimization of small-molecule ligands for the CBP/p300 bromodomains J. Am. Chem. Soc. 2014, 136, 9308-9319 10.1021/ja412434f
159. Picaud, S.; Fedorov, O.; Thanasopoulou, A.; Leonards, K.; Jones, K.; Meier, J.; Olzscha, H.; Monteiro, O.; Martin, S.; Philpott, M.; Tumber, A.; Filippakopoulos, P.; Yapp, C.; Wells, C.; Che, K. H.; Bannister, A.; Robson, S.; Kumar, U.; Parr, N.; Lee, K.; Lugo, D.; Jeffrey, P.; Taylor, S.; Vecellio, M. L.; Bountra, C.; Brennan, P. E.; O'Mahony, A.; Velichko, S.; Muller, S.; Hay, D.; Daniels, D. L.; Urh, M.; La Thangue, N. B.; Kouzarides, T.; Prinjha, R.; Schwaller, J.; Knapp, S. Generation of a selective small molecule inhibitor of the CBP/p300 bromodomain for leukemia therapy Cancer Res. 2015, 75, 5106-5119 10.1158/0008-5472.CAN-15-0236
160. Arrowsmith, C. H.; Bountra, C.; Fish, P. V.; Lee, K.; Schapira, M. Epigenetic protein families: a new frontier for drug discovery Nat. Rev. Drug Discovery 2012, 11, 384-400 10.1038/nrd3674
161. Hilton, I. B.; D'Ippolito, A. M.; Vockley, C. M.; Thakore, P. I.; Crawford, G. E.; Reddy, T. E.; Gersbach, C. A. Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers Nat. Biotechnol. 2015, 33, 510-517 10.1038/nbt.3199
162. Mottamal, M.; Zheng, S.; Huang, T. L.; Wang, G. Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents Molecules 2015, 20, 3898-3941 10.3390/molecules20033898
163. Filippakopoulos, P.; Qi, J.; Picaud, S.; Shen, Y.; Smith, W. B.; Fedorov, O.; Morse, E. M.; Keates, T.; Hickman, T. T.; Felletar, I.; Philpott, M.; Munro, S.; McKeown, M. R.; Wang, Y.; Christie, A. L.; West, N.; Cameron, M. J.; Schwartz, B.; Heightman, T. D.; La Thangue, N.; French, C. A.; Wiest, O.; Kung, A. L.; Knapp, S.; Bradner, J. E. Selective inhibition of BET bromodomains Nature 2010, 468, 1067-1073 10.1038/nature09504
164. Brand, M.; Measures, A. M.; Wilson, B. G.; Cortopassi, W. A.; Alexander, R.; Hoss, M.; Hewings, D. S.; Rooney, T. P.; Paton, R. S.; Conway, S. J. Small molecule inhibitors of bromodomain-acetyl-lysine interactions ACS Chem. Biol. 2015, 10, 22-39 10.1021/cb500996u
165. Andreotti, G.; Monticelli, M.; Cubellis, M. V. Looking for protein stabilizing drugs with thermal shift assay Drug Test. Anal. 2015, 7, 831-834 10.1002/dta.1798
166. Jerabek-Willemsen, M.; Andre, T.; Wanner, R.; Roth, H. M.; Duhr, S.; Baaske, P.; Breitsprecher, D. MicroScale Thermophoresis: Interaction analysis and beyond J. Mol. Struct. 2014, 1077, 101-113 10.1016/j.molstruc.2014.03.009
167. Baell, J. B.; Holloway, G. A. New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays J. Med. Chem. 2010, 53, 2719-2740 10.1021/jm901137j
168. Pan, Z.; Scheerens, H.; Li, S. J.; Schultz, B. E.; Sprengeler, P. A.; Burrill, L. C.; Mendonca, R. V.; Sweeney, M. D.; Scott, K. C.; Grothaus, P. G.; Jeffery, D. A.; Spoerke, J. M.; Honigberg, L. A.; Young, P. R.; Dalrymple, S. A.; Palmer, J. T. Discovery of selective irreversible inhibitors for Bruton's tyrosine kinase ChemMedChem 2007, 2, 58-61 10.1002/cmdc.200600221
169. Arrowsmith, C. H.; Audia, J. E.; Austin, C.; Baell, J.; Bennett, J.; Blagg, J.; Bountra, C.; Brennan, P. E.; Brown, P. J.; Bunnage, M. E.; Buser-Doepner, C.; Campbell, R. M.; Carter, A. J.; Cohen, P.; Copeland, R. A.; Cravatt, B.; Dahlin, J. L.; Dhanak, D.; Edwards, A. M.; Frederiksen, M.; Frye, S. V.; Gray, N.; Grimshaw, C. E.; Hepworth, D.; Howe, T.; Huber, K. V.; Jin, J.; Knapp, S.; Kotz, J. D.; Kruger, R. G.; Lowe, D.; Mader, M. M.; Marsden, B.; Mueller-Fahrnow, A.; Muller, S.; O'Hagan, R. C.; Overington, J. P.; Owen, D. R.; Rosenberg, S. H.; Roth, B.; Ross, R.; Schapira, M.; Schreiber, S. L.; Shoichet, B.; Sundstrom, M.; Superti-Furga, G.; Taunton, J.; Toledo-Sherman, L.; Walpole, C.; Walters, M. A.; Willson, T. M.; Workman, P.; Young, R. N.; Zuercher, W. J. The promise and peril of chemical probes Nat. Chem. Biol. 2015, 11, 536-541 10.1038/nchembio.1867
170. Scholz, C.; Weinert, B. T.; Wagner, S. A.; Beli, P.; Miyake, Y.; Qi, J.; Jensen, L. J.; Streicher, W.; McCarthy, A. R.; Westwood, N. J.; Lain, S.; Cox, J.; Matthias, P.; Mann, M.; Bradner, J. E.; Choudhary, C. Acetylation site specificities of lysine deacetylase inhibitors in human cells Nat. Biotechnol. 2015, 33, 415-423 10.1038/nbt.3130
171. Glozak, M. A.; Sengupta, N.; Zhang, X.; Seto, E. Acetylation and deacetylation of non-histone proteins Gene 2005, 363, 15-23 10.1016/j.gene.2005.09.010
172. Singh, B. N.; Zhang, G. H.; Hwa, Y. L.; Li, J. P.; Dowdy, S. C.; Jiang, S. W. Nonhistone protein acetylation as cancer therapy targets Expert Rev. Anticancer Ther. 2010, 10, 935-954 10.1586/era.10.62
173. Weinert, B. T.; Scholz, C.; Wagner, S. A.; Iesmantavicius, V.; Su, D.; Daniel, J. A.; Choudhary, C. Lysine succinylation is a frequently occurring modification in prokaryotes and eukaryotes and extensively overlaps with acetylation Cell Rep. 2013, 4, 842-851 10.1016/j.celrep.2013.07.024
174. Baeza, J.; Smallegan, M. J.; Denu, J. M. Site-specific reactivity of nonenzymatic lysine acetylation ACS Chem. Biol. 2015, 10, 122-128 10.1021/cb500848p
175. Weinert, B. T.; Moustafa, T.; Iesmantavicius, V.; Zechner, R.; Choudhary, C. Analysis of acetylation stoichiometry suggests that SIRT3 repairs nonenzymatic acetylation lesions EMBO J. 2015, 34, 2620-2632 10.15252/embj.201591271