RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain

Proceedings of the National Academy of Sciences of the United States of America

Volumn 110, Issue 49, 2013, Pages 19754-19759

  Picaud, Sarah ^a   Wells, Christopher ^a   Felletar, Ildiko ^a   Brotherton, Deborah ^a   Martin, Sarah ^a   Savitsky, Pavel ^a   Diez Dacal, Beatriz ^a   Philpott, Martin ^a   Bountra, Chas ^a   Lingard, Hannah ^a   Fedorov, Oleg ^a   Müller, Susanne ^a   Brennan, Paul E ^a   Knapp, Stefan ^a   Filippakopoulos, Panagis ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BROMO AND EXTRATERMINAL PROTEIN; PROTEIN; PROTEIN INHIBITOR; RVX 208; UNCLASSIFIED DRUG;

ARTICLE; BLEACHING; BROMODOMAIN; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG SELECTIVITY; GENE EXPRESSION; GENETIC TRANSCRIPTION; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FUNCTION;

EID: 84889663966     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1310658110     Document Type: Article

References (48)

1. Filippakopoulos P, et al. (2012) Histone recognition and large-scale structural analysis of the human bromodomain family. Cell 149(1):214-231
2. Vidler LR, Brown N, Knapp S, Hoelder S (2012) Druggability analysis and structural classification of bromodomain acetyl-lysine binding sites. J Med Chem 55(17): 7346-7359
3. Muller S, Filippakopoulos P, Knapp S (2011) Bromodomains as therapeutic targets. Expert Rev Mol Med 13:e29
4. Dhalluin C, et al. (1999) Structure and ligand of a histone acetyltransferase bromodomain. Nature 399(6735):491-496
5. Owen DJ, et al. (2000) The structural basis for the recognition of acetylated histone H4 by the bromodomain of histone acetyltransferase gcn5p. EMBO J 19(22):6141-6149
6. Morinière J, et al. (2009) Cooperative binding of two acetylation marks on a histone tail by a single bromodomain. Nature 461(7264):664-668
7. Filippakopoulos P, et al. (2010) Selective inhibition of BET bromodomains. Nature 468(7327):1067-1073
8. Dawson MA, et al. (2011) Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature 478(7370):529-533
9. Nicodeme E, et al. (2010) Suppression of inflammation by a synthetic histone mimic. Nature 468(7327):1119-1123
10. Fish PV, et al. (2012) Identification of a chemical probe for bromo and extra C-terminal bromodomain inhibition through optimization of a fragment-derived hit. J Med Chem 55(22):9831-9837
11. Maruyama T, et al. (2002) A mammalian bromodomain protein, Brd4, interacts with replication factor C and inhibits progression to S phase. Mol Cell Biol 22(18):6509-6520
12. Dey A, Nishiyama A, Karpova T, McNally J, Ozato K (2009) Brd4 marks select genes on mitotic chromatin and directs postmitotic transcription. Mol Biol Cell 20(23): 4899-4909
13. French CA (2012) Pathogenesis of NUT midline carcinoma. Annu Rev Pathol 7: 247-265
14. Rahl PB, et al. (2010) c-Myc regulates transcriptional pause release. Cell 141(3): 432-445
15. You J, et al. (2009) Regulation of aurora B expression by the bromodomain protein Brd4. Mol Cell Biol 29(18):5094-5103
16. Delmore JE, et al. (2011) BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 146(6):904-917
17. Zuber J, et al. (2011) RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature 478(7370):524-528
18. Lockwood WW, Zejnullahu K, Bradner JE, Varmus H (2012) Sensitivity of human lung adenocarcinoma cell lines to targeted inhibition of BET epigenetic signaling proteins. Proc Natl Acad Sci USA 109(47):19408-19413
19. Cheng Z, et al. (2013) Inhibition of BET bromodomain targets genetically diverse glioblastoma. Clin Cancer Res 19(7):1748-1759
20. Bartholomeeusen K, Xiang Y, Fujinaga K, Peterlin BM (2012) Bromodomain and extraterminal (BET) bromodomain inhibition activate transcription via transient release of positive transcription elongation factor b (P-TEFb) from 7SK small nuclear ribonucleoprotein. J Biol Chem 287(43):36609-36616
21. Zhang W, et al. (2012) Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase 2 serine 2 phosphorylation in human CD4+ T cells. J Biol Chem 287(51): 43137-43155
22. Chen R, Liu M, Zhang K, Zhou Q (2011) Isolation and functional characterization of P-TEFb-associated factors that control general and HIV-1 transcriptional elongation. Methods 53(1):85-90
23. Gamsjaeger R, et al. (2011) Structural basis and specificity of acetylated transcription factor GATA1 recognition by BET family bromodomain protein Brd3. Mol Cell Biol 31(13):2632-2640
24. Denis GV (2010) Bromodomain coactivators in cancer, obesity, type 2 diabetes, and inflammation. Discov Med 10(55):489-499
25. Wang F, et al. (2010) Brd2 disruption in mice causes severe obesity without Type 2 diabetes. Biochem J 425(1):71-83
26. Shang E, Nickerson HD, Wen D, Wang X, Wolgemuth DJ (2007) The first bromodomain of Brdt, a testis-specific member of the BET sub-family of double-bromodomaincontaining proteins, is essential for male germ cell differentiation. Development 134(19):3507-3515
27. Bailey D, et al. (2010) RVX-208: A small molecule that increases apolipoprotein A-1 and high-density lipoprotein cholesterol in vitro and in vivo. J Am Coll Cardiol 55(23): 2580-2589
28. Nicholls SJ, et al. (2012) ApoA-1 induction as a potential cardioprotective strategy: Rationale for the SUSTAIN and ASSURE studies. Cardiovasc Drugs Ther 26(2):181-187
29. McNeill E (2010) RVX-208, a stimulator of apolipoprotein A1 gene expression for the treatment of cardiovascular diseases. Curr Opin Investig Drugs 11(3):357-364
30. Joy TR (2012) Novel HDL-based therapeutic agents. Pharmacol Ther 135(1):18-30
31. Chung CW, et al. (2011) Discovery and characterization of small molecule inhibitors of the BET family bromodomains. J Med Chem 54(11):3827-3838
32. Mirguet O, et al. (2012) From ApoA1 upregulation to BET family bromodomain inhibition: Discovery of 1-BET151. Bioorg Med Chem Lett 22(8):2963-2967
33. Hansen H (2008) Compounds for the prevention and treatment of cardiovascular diseases. International Patent WO 2008/092231 A1
34. Bamborough P, et al. (2012) Fragment-based discovery of bromodomain inhibitors part 2: optimization of phenylisoxazole sulfonamides. J Med Chem 55(2):587-596
35. Picaud S, et al. (2013) PFI-1, a highly selective protein interaction inhibitor, targeting BET Bromodomains. Cancer Res 73(11):3336-3346
36. Yang Z, et al. (2005) Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4. Mol Cell 19(4):535-545
37. Gaucher J, et al. (2012) Bromodomain-dependent stage-specific male genome programming by Brdt. EMBO J 31(19):3809-3820
38. Matzuk MM, et al. (2012) Small-molecule inhibition of BRDT for male contraception. Cell 150(4):673-684
39. Berkovits BD, Wolgemuth DJ (2011) The first bromodomain of the testis-specific double bromodomain protein Brdt is required for chromocenter organization that is modulated by genetic background. Dev Biol 360(2):358-368
40. Lamonica JM, et al. (2011) Bromodomain protein Brd3 associates with acetylated GATA1 to promote its chromatin occupancy at erythroid target genes. Proc Natl Acad Sci USA 108(22):E159-E168
41. Tsume M, et al. (2012) Brd2 is required for cell cycle exit and neuronal differentiation through the E2F1 pathway in mouse neuroepithelial cells. Biochem Biophys Res Commun 425(4):762-768
42. Wu SY, Lee AY, Lai HT, Zhang H, Chiang CM (2013) Phospho switch triggers Brd4 chromatin binding and activator recruitment for gene-specific targeting. Mol Cell 49(5):843-857
43. Tillett D, Neilan BA (1999) Enzyme-free cloning: A rapid method to clone PCR products independent of vector restriction enzyme sites. Nucleic Acids Res 27(19):e26
44. Hansen HC, Wagner GS, Attwell SC, McLure KG, Kulikowski EB (2010) Novel anti-inflammatory agents. International Patent WO 2010/123975 A1
45. Wigle TJ, et al. (2010) Screening for inhibitors of low-affinity epigenetic peptideprotein interactions: An AlphaScreen-based assay for antagonists of methyl-lysine binding proteins. J Biomol Screen 15(1):62-71
46. Gentleman RC, et al. (2004) Bioconductor: Open software development for computational biology and bioinformatics. Genome Biol 5(10):R80
47. Irizarry RA, et al. (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4(2):249-264
48. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: A practical and powerful approach to multiple testing. J R Stat Soc, B 57(1):289-300