Progress in the discovery of small-molecule inhibitors of bromodomain-histone interactions

Journal of Biomolecular Screening

Volumn 16, Issue 10, 2011, Pages 1170-1185

  Chung, Chun Wa ^a   Witherington, Jason ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

AlphaLISA; AlphaScreen; bromodomains; crystallography; epigenetics; fluorescence anisotropy; histone acetyl lysine reader domains; histone binding proteins; ITC; NMR; TR FRET

Indexed keywords

BROMINE DERIVATIVE; HISTONE; PROTEIN INHIBITOR; SMALL MOLECULE TRANSPORT AGENT;

BINDING ASSAY; DNA HISTONE INTERACTION; EPIGENETICS; FLUOROMETRY; HUMAN; IN VITRO STUDY; MOLECULAR LIBRARY; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DOMAIN; REVIEW; SURFACE PLASMON RESONANCE;

ANIMALS; DRUG DISCOVERY; HIGH-THROUGHPUT SCREENING ASSAYS; HISTONE ACETYLTRANSFERASES; HISTONES; HUMANS; PROTEIN BINDING; PROTEIN STRUCTURE, TERTIARY;

EID: 83455202613     PISSN: 10870571     EISSN: 1552454X     Source Type: Journal    
DOI: 10.1177/1087057111421372     Document Type: Review

References (82)

1. Nicodeme E., Jeffrey K. L., Schaefer U., Beinke S., Dewell S., Chung C. W., Chandwani R., Marazzi I., Wilson P., Coste H., et al. Suppression of Inflammation by a Synthetic Histone Mimic. Nature. 2010 ; 468: 1119-1123
2. Gerona-Navarro G., Yoel R., Mujtaba S., Frasca A., Patel J., Zeng L., Plotnikov A. N., Osman R., Zhou M. M.. Rational Design of Cyclic Peptide Modulators of the Transcriptional Coactivator CBP: A New Class of p53 Inhibitors. J. Am. Chem. Soc. 2011 ; 133: 2040-2043
3. 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 (Pubitemid 43099926)
4. Zeng L., Li J., Muller M., Yan S., Mujtaba S., Pan C., Wang Z., Zhou M. M.. Selective Small Molecules Blocking HIV-1 Tat and Coactivator PCAF Association. J. Am. Chem. Soc. 2005 ; 127: 2376-2377 (Pubitemid 40327786)
5. Filippakopoulos P., Qi J., Picaud S., Shen Y., Smith W. B., Fedorov O., Morse E. M., Keates T., Hickman T. T., Felletar I., et al. Selective Inhibition of BET Bromodomains. Nature. 2010 ; 468: 1067-1073
6. Ito T., Umehara T., Sasaki K., Nakamura Y., Nishino N., Terada T., Shirouzu M., Padmanabhan B., Yokoyama S., Ito A., et al. Real-Time Imaging of Histone H4K12-Specific Acetylation Determines the Modes of Action of Histone Deacetylase and Bromodomain Inhibitors. Chem. Biol. 2011 ; 18: 495-507
7. Herold J. M., Wigle T. J., Norris J. L., Lam R., Korboukh V. K., Gao C., Ingerman L. A., Kireev D. B., Senisterra G., Vedadi M., et al. Small-Molecule Ligands of Methyl-Lysine Binding Proteins. J. Med. Chem. 2011 ; 54: 2504-2511
8. Kireev D., Wigle T. J., Norris-Drouin J., Herold J. M., Janzen W. P., Frye S. V.. Identification of Non-Peptide Malignant Brain Tumor (MBT) Repeat Antagonists by Virtual Screening of Commercially Available Compounds. J. Med. Chem. 2010 ; 53: 7625-7631
9. Tamkun J. W., Deuring R., Scott M. P., Kissinger M., Pattatucci A. M., Kaufman T. C., Kennison J. A.. brahma: A Regulator of Drosophila Homeotic Genes Structurally Related to the Yeast Transcriptional Activator SNF2/SWI2. Cell. 1992 ; 68: 561-572
10. Florence B., Faller D. V.. You Bet-Cha: A Novel Family of Transcriptional Regulators. Front. Biosci. 2001 ; 6: D1008 - D1018
11. Nicolas R. H., Goodwin G. H.. Molecular Cloning of Polybromo, a Nuclear Protein Containing Multiple Domains Including Five Bromodomains, a Truncated HMG-box, and Two Repeats of a Novel Domain. Gene. 1996 ; 175: 233-240 (Pubitemid 26367792)
12. Thompson M.. Polybromo-1: The Chromatin Targeting Subunit of the PBAF Complex. Biochimie. 2009 ; 91: 309-319
13. Denis G. V.. Bromodomain Coactivators in Cancer, Obesity, Type 2 Diabetes, and Inflammation. Discov. Med. 2010 ; 10: 489-499
14. Sanchez R., Zhou M. M.. The Role of Human Bromodomains in Chromatin Biology and Gene Transcription. Curr. Opin. Drug Discov. Dev. 2009 ; 12: 659-665
15. Greenwald R. J., Tumang J. R., Sinha A., Currier N., Cardiff R. D., Rothstein T. L., Faller D. V., Denis G. V.. E mu-BRD2 Transgenic Mice Develop B-Cell Lymphoma and Leukemia. Blood. 2004 ; 103: 1475-1484 (Pubitemid 38168665)
16. French C. A., Miyoshi I., Aster J. C., Kubonishi I., Kroll T. G., Dal C. P., Vargas S. O., Perez-Atayde A. R., Fletcher J. A.. BRD4 Bromodomain Gene Rearrangement in Aggressive Carcinoma with Translocation t(15;19). Am. J. Pathol. 2001 ; 159: 1987-1992 (Pubitemid 33104253)
17. French C. A.. NUT Midline Carcinoma. Cancer Genet. Cytogenet. 2010 ; 203: 16-20
18. Schwartz B. E., Hofer M. D., Lemieux M. E., Bauer D. E., Cameron M. J., West N. H., Agoston E. S., Reynoird N., Khochbin S., Ince T. A., et al. Differentiation of NUT Midline Carcinoma by Epigenomic Reprogramming. Cancer Res. 2011 ; 71: 2686-2696
19. Reynoird N., Schwartz B. E., Delvecchio M., Sadoul K., Meyers D., Mukherjee C., Caron C., Kimura H., Rousseaux S., Cole P. A., et al. Oncogenesis by Sequestration of CBP/p300 in Transcriptionally Inactive Hyperacetylated Chromatin Domains. EMBO J. 2010 ; 29: 2943-2952
20. Huang B., Yang X. D., Zhou M. M., Ozato K., Chen L. F.. Brd4 Coactivates Transcriptional Activation of NF-kappaB via Specific Binding to Acetylated RelA. Mol. Cell Biol. 2009 ; 29: 1375-1387
21. Hargreaves D. C., Horng T., Medzhitov R.. Control of Inducible Gene Expression by Signal-Dependent Transcriptional Elongation. Cell. 2009 ; 138: 129-145
22. Chung C. W., Coste H., White J. H., Mirguet O., Wilde J., Gosmini R. L., Delves C., Magny S. M., Woodward R., Hughes S. A., et al. Discovery and Characterization of Small Molecule Inhibitors of the BET Family Bromodomains. J. Med. Chem. 2011 ; 54: 3827-3838
23. McBride A. A., McPhillips M. G., Oliveira J. G.. Brd4: Tethering, Segregation and Beyond. Trends Microbiol. 2004 ; 12: 527-529 (Pubitemid 39469898)
24. McPhillips M. G., Oliveira J. G., Spindler J. E., Mitra R., McBride A. A.. Brd4 Is Required for e2-Mediated Transcriptional Activation but Not Genome Partitioning of All Papillomaviruses. J. Virol. 2006 ; 80: 9530-9543 (Pubitemid 44435629)
25. Rahman S., Sowa M. E., Ottinger M., Smith J. A., Shi Y., Harper J. W., Howley P. M.. The Brd4 Extraterminal Domain Confers Transcription Activation Independent of pTEFb by Recruiting Multiple Proteins, Including NSD3. Mol. Cell Biol. 2011 ; 31: 2641-2652
26. Dorr A., Kiermer V., Pedal A., Rackwitz H. R., Henklein P., Schubert U., Zhou M. M., Verdin E., Ott M.. Transcriptional Synergy between Tat and PCAF Is Dependent on the Binding of Acetylated Tat to the PCAF Bromodomain. EMBO J. 2002 ; 21: 2715-2723 (Pubitemid 34619387)
27. Ott M., Dorr A., Hetzer-Egger C., Kaehlcke K., Schnolzer M., Henklein P., Cole P., Zhou M. M., Verdin E.. Tat Acetylation: A Regulatory Switch between Early and Late Phases in HIV Transcription Elongation. Novartis Found. Symp. 2004 ; 259: 182-193
28. Ciro M., Prosperini E., Quarto M., Grazini U., Walfridsson J., McBlane F., Nucifero P., Pacchiana G., Capra M., Christensen J., et al. ATAD2 Is a Novel Cofactor for MYC, Overexpressed and Amplified in Aggressive Tumors. Cancer Res. 2009 ; 69: 8491-8498
29. Zou J. X., Guo L., Revenko A. S., Tepper C. G., Gemo A. T., Kung H. J., Chen H. W.. Androgen-Induced Coactivator ANCCA Mediates Specific Androgen Receptor Signaling in Prostate Cancer. Cancer Res. 2009 ; 69: 3339-3346
30. Kalashnikova E. V., Revenko A. S., Gemo A. T., Andrews N. P., Tepper C. G., Zou J. X., Cardiff R. D., Borowsky A. D., Chen H. W.. ANCCA/ATAD2 Overexpression Identifies Breast Cancer Patients with Poor Prognosis, Acting to Drive Proliferation and Survival of Triple-Negative Cells through Control of B-Myb and EZH2. Cancer Res. 2010 ; 70: 9402-9412
31. Revenko A. S., Kalashnikova E. V., Gemo A. T., Zou J. X., Chen H. W.. Chromatin Loading of E2F-MLL Complex by Cancer-Associated Coregulator ANCCA via Reading a Specific Histone Mark. Mol. Cell Biol. 2010 ; 30: 5260-5272
32. Kwok R. P., Lundblad J. R., Chrivia J. C., Richards J. P., Bachinger H. P., Brennan R. G., Roberts S. G., Green M. R., Goodman R. H.. Nuclear Protein CBP Is a Coactivator for the Transcription Factor CREB. Nature. 1994 ; 370: 223-226 (Pubitemid 24236779)
33. Mujtaba S., He Y., Zeng L., Yan S., Plotnikova O., Sachchidanand , Sanchez R., Zeleznik-Le N. J., Ronai Z., Zhou M. M.. Structural Mechanism of the Bromodomain of the Coactivator CBP in p53 Transcriptional Activation. Mol. Cell. 2004 ; 13: 251-263 (Pubitemid 38183271)
34. Xiao X., Li B. X., Mitton B., Ikeda A., Sakamoto K. M.. Targeting CREB for Cancer Therapy: Friend or Foe. Curr. Cancer Drug Targets. 2010 ; 10: 384-391
35. Nayak S. K., Panesar P. S., Kumar H.. p53-Induced Apoptosis and Inhibitors of p53. Curr. Med. Chem. 2009 ; 16: 2627-2640
36. Li J., Ghiani C. A., Kim J. Y., Liu A., Sandoval J., DeVellis J., Casaccia-Bonnefil P.. Inhibition of p53 Transcriptional Activity: A Potential Target for Future Development of Therapeutic Strategies for Primary Demyelination. J. Neurosci. 2008 ; 28: 6118-6127
37. Gudkov A. V., Komarova E. A.. Pathologies Associated with the p53 Response. Cold Spring Harb. Perspect. Biol. 2010 ; 2: a001180
38. Borah J. C., Mujtaba S., Karakikes I., Zeng L., Muller M., Patel J., Moshkina N., Morohashi K., Zhang W., Gerona-Navarro G., et al. A Small Molecule Binding to the Coactivator CREB-Binding Protein Blocks Apoptosis in Cardiomyocytes. Chem. Biol. 2011 ; 18: 531-541
39. Dhalluin C., Carlson J. E., Zeng L., He C., Aggarwal A. K., Zhou M. M.. Structure and Ligand of a Histone Acetyltransferase Bromodomain. Nature. 1999 ; 399: 491-496 (Pubitemid 29258857)
40. Vollmuth F., Geyer M. Angew Chem. Int. Ed. Engl. 2010: 6768-6772.
41. Barlev N. A., Liu L., Chehab N. H., Mansfield K., Harris K. G., Halazonetis T. D., Berger S. L.. Acetylation of p53 Activates Transcription through Recruitment of Coactivators/Histone Acetyltransferases. Mol. Cell. 2001 ; 8: 1243-1254 (Pubitemid 34084996)
42. Comley J.. Progress in the Implementation of Label Free Detection. Drug Discov. World. 2008 ;: 28-49
43. Hajduk P. J.. SAR by NMR: Putting the Pieces Together. Mol. Interv. 2006 ; 6: 266-272 (Pubitemid 44556047)
44. Shuker S. B., Hajduk P. J., Meadows R. P., Fesik S. W.. Discovering High-Affinity Ligands for Proteins: SAR by NMR. Science. 1996 ; 274: 1531-1534 (Pubitemid 26403929)
45. Shapiro M. J., Wareing J. R.. High Resolution NMR for Screening Ligand/Protein Binding. Curr. Opin. Drug Discov. Dev. 1999 ; 2: 396-400 (Pubitemid 29372364)
46. Danielson U. H.. Fragment Library Screening and Lead Characterization Using SPR Biosensors. Curr. Top Med. Chem. 2009 ; 9: 1725-1735
47. Boettcher A., Ruedisser S., Erbel P., Vinzenz D., Schiering N., Hassiepen U., Rigollier P., Mayr L. M., Woelcke J.. Fragment-Based Screening by Biochemical Assays: Systematic Feasibility Studies with Trypsin and MMP12. J. Biomol. Screen. 2010 ; 15: 1029-1041
48. Perspicace S., Banner D., Benz J., Muller F., Schlatter D., Huber W.. Fragment-Based Screening Using Surface Plasmon Resonance Technology. J. Biomol. Screen. 2009 ; 14: 337-349
49. Navratilova I., Hopkins A. L.. Fragment Screening by Surface Plasmon Resonance. ACS Med. Chem. Lett. 2010 ; 1: 44-48
50. Neumann T., Junker H. D., Schmidt K., Sekul R.. SPR-Based Fragment Screening: Advantages and Applications. Curr. Top Med. Chem. 2007 ; 7: 1630-1642 (Pubitemid 350131018)
51. Jung S. O., Ro H. S., Kho B. H., Shin Y. B., Kim M. G., Chung B. H.. Surface Plasmon Resonance Imaging-Based Protein Arrays for High-Throughput Screening of Protein-Protein Interaction Inhibitors. Proteomics. 2005 ; 5: 4427-4431 (Pubitemid 41739920)
52. Giannetti A. M.. From Experimental Design to Validated Hits a Comprehensive Walk-Through of Fragment Lead Identification Using Surface Plasmon Resonance. Methods Enzymol. 2011 ; 493: 169-218
53. Cummings M. D., Farnum M. A., Nelen M. I.. Universal Screening Methods and Applications of ThermoFluor. J. Biomol. Screen. 2006 ; 11: 854-863 (Pubitemid 44562327)
54. Niesen F. H., Berglund H., Vedadi M.. The Use of Differential Scanning Fluorimetry to Detect Ligand Interactions That Promote Protein Stability. Nat. Protoc. 2007 ; 2: 2212-2221 (Pubitemid 351565860)
55. Pantoliano M. W., Petrella E. C., Kwasnoski J. D., Lobanov V. S., Myslik J., Graf E., Carver T., Asel E., Springer B. A., Lane P., et al. High-Density Miniaturized Thermal Shift Assays as a General Strategy for Drug Discovery. J. Biomol. Screen. 2001 ; 6: 429-440 (Pubitemid 34052847)
56. Ericsson U. B., Hallberg B. M., Detitta G. T., Dekker N., Nordlund P.. Thermofluor-Based High-Throughput Stability Optimization of Proteins for Structural Studies. Anal. Biochem. 2006 ; 357: 289-298 (Pubitemid 44430091)
57. Holdgate G. A., Ward W. H.. Measurements of Binding Thermodynamics in Drug Discovery. Drug Discov. Today. 2005 ; 10: 1543-1550 (Pubitemid 41527197)
58. Waldron T. T., Murphy K. P.. Stabilization of Proteins by Ligand Binding: Application to Drug Screening and Determination of Unfolding Energetics. Biochemistry. 2003 ; 42: 5058-5064 (Pubitemid 36532060)
59. Vedadi M., Arrowsmith C. H., Allali-Hassani A., Senisterra G., Wasney G. A.. Biophysical Characterization of Recombinant Proteins: A Key to Higher Structural Genomics Success. J. Struct. Biol. 2010 ; 172: 107-119
60. Fedorov O., Marsden B., Pogacic V., Rellos P., Muller S., Bullock A. N., Schwaller J., Sundstrom M., Knapp S.. A Systematic Interaction Map of Validated Kinase Inhibitors with Ser/Thr Kinases. Proc. Natl. Acad. Sci. U. S. A. 2007 ; 104: 20523-20528
61. Horn J. R., Shoichet B. K.. Allosteric Inhibition through Core Disruption. J. Mol. Biol. 2004 ; 336: 1283-1291 (Pubitemid 38229713)
62. Zhang Q., Chakravarty S., Ghersi D., Zeng L., Plotnikov A. N., Sanchez R., Zhou M. M.. Biochemical Profiling of Histone Binding Selectivity of the Yeast Bromodomain Family. PLoS One. 2010 ; 5: e8903
63. Nady N., Min J., Kareta M. S., Chedin F., Arrowsmith C. H.. A SPOT on the Chromatin Landscape? Histone Peptide Arrays as a Tool for Epigenetic Research. Trends Biochem. Sci. 2008 ; 33: 305-313
64. Garske A. L., Craciun G., Denu J. M.. A Combinatorial H4 Tail Library for Exploring the Histone Code. Biochemistry. 2008 ; 47: 8094-8102
65. Ullman E. F., Kirakossian H., Switchenko A. C., Ishkanian J., Ericson M., Wartchow C. A., Pirio M., Pease J., Irvin B. R., Singh S., et al. Luminescent Oxygen Channeling Assay (LOCI): Sensitive, Broadly Applicable Homogeneous Immunoassay Method. Clin. Chem. 1996 ; 42: 1518-1526 (Pubitemid 26300260)
66. Ullman E. F., Kirakossian H., Singh S., Wu Z. P., Irvin B. R., Pease J. S., Switchenko A. C., Irvine J. D., Dafforn A., Skold C. N.. Luminescent Oxygen Channeling Immunoassay: Measurement of Particle Binding Kinetics by Chemiluminescence. Proc. Natl. Acad. Sci. U. S. A. 1994 ; 91: 5426-5430 (Pubitemid 24174340)
67. Quinn A. M., Bedford M. T., Espejo A., Spannhoff A., Austin C. P., Oppermann U., Simeonov A.. A Homogeneous Method for Investigation of Methylation-Dependent Protein-Protein Interactions in Epigenetics. Nucleic Acids Res. 2010 ; 38: e11
68. Wigle T. J., Herold J. M., Senisterra G. A., Vedadi M., Kireev D. B., Arrowsmith C. H., Frye S. V., Janzen W. P.. Screening for Inhibitors of Low-Affinity Epigenetic Peptide-Protein Interactions: An AlphaScreen-Based Assay for Antagonists of Methyl-Lysine Binding Proteins. J. Biomol. Screen. 2010 ; 15: 62-71
69. Fischle W., Wang Y., Jacobs S. A., Kim Y., Allis C. D., Khorasanizadeh S.. Molecular Basis for the Discrimination of Repressive Methyl-Lysine Marks in Histone H3 by Polycomb and HP1 Chromodomains. Genes Dev. 2003 ; 17: 1870-1881 (Pubitemid 36944564)
70. Mills N. L., Shelat A. A., Guy R. K.. Assay Optimization and Screening of RNA-Protein Interactions by AlphaScreen. J. Biomol. Screen. 2007 ; 12: 946-955 (Pubitemid 47548591)
71. Min J., Allali-Hassani A., Nady N., Qi C., Ouyang H., Liu Y., MacKenzie F., Vedadi M., Arrowsmith C. H.. L3MBTL1 Recognition of Mono- and Dimethylated Histones. Nat. Struct. Mol. Biol. 2007 ; 14: 1229-1230 (Pubitemid 350223338)
72. Chandrasekaran R., Thompson M.. Polybromo-1-Bromodomains Bind Histone H3 at Specific Acetyl-Lysine Positions. Biochem. Biophys. Res. Commun. 2007 ; 355: 661-666 (Pubitemid 46330204)
73. Chandrasekaran R., Thompson M.. Expression, Purification and Characterization of Individual Bromodomains from Human Polybromo-1. Protein Expr. Purif. 2006 ; 50: 111-117 (Pubitemid 44648752)
74. Kupitz C., Chandrasekaran R., Thompson M.. Kinetic Analysis of Acetylation-Dependent Pb1 Bromodomain-Histone Interactions. Biophys. Chem. 2008 ; 136: 7-12
75. Thompson M., Chandrasekaran R.. Thermodynamic Analysis of Acetylation-Dependent Pb1 Bromodomain-Histone H3 Interactions. Anal. Biochem. 2008 ; 374: 304-312
76. Charlop-Powers Z., Zeng L., Zhang Q., Zhou M. M.. Structural Insights into Selective Histone H3 Recognition by the Human Polybromo Bromodomain 2. Cell Res. 2010 ; 20: 529-538
77. Padilla-Parra S., Auduge N., Coppey-Moisan M., Tramier M.. Quantitative FRET Analysis by Fast Acquisition Time Domain FLIM at High Spatial Resolution in Living Cells. Biophys. J. 2008 ; 95: 2976-2988
78. Nishiyama A., Mochizuki K., Mueller F., Karpova T., McNally J. G., Ozato K.. Intracellular Delivery of Acetyl-Histone Peptides Inhibits Native Bromodomain-Chromatin Interactions and Impairs Mitotic Progression. FEBS Lett. 2008 ; 582: 1501-1507
79. Kanno T., Kanno Y., Siegel R. M., Jang M. K., Lenardo M. J., Ozato K.. Selective Recognition of Acetylated Histones by Bromodomain Proteins Visualized in Living Cells. Mol. Cell. 2004 ; 13: 33-43 (Pubitemid 38117113)
80. Sueoka H., Ehara S., Kobayashi H., Arichi T., Komatsu H.. Thienotriazolodiazepine Compounds and Their Pharmaceutical Use As Cell Adhesion Inhibitors.. 1998 ;:
81. Adachi K., Hikawa H., Hamada M., Endoh J.-I., Ishibuchi S., Fujie N., Tanaka M., Sugahara K., Oshita K., Murata M.. Preparation of Thienotriazolodiazepine Compounds Having an Action of Inhibiting the CD28 Costimulatory Signal in T Cell.. 2006 ;:
82. Miyoshi S., Ooike S., Iwata K., Hikawa H., Sugahara K.. Antitumor Agent.. 2009 ;: