Fragment-Based Discovery of Low-Micromolar ATAD2 Bromodomain Inhibitors

Journal of Medicinal Chemistry

Volumn 58, Issue 14, 2015, Pages 5649-5673

  Demont, Emmanuel H ^a   Chung, Chun Wa ^b   Furze, Rebecca C ^a   Grandi, Paola ^a   Michon, Anne Marie ^a   Wellaway, Chris ^a   Barrett, Nathalie ^b   Bridges, Angela M ^b   Craggs, Peter D ^b   Diallo, Hawa ^a   Dixon, David P ^b   Douault, Clement ^a   Emmons, Amanda J ^b   Jones, Emma J ^b   Karamshi, Bhumika V ^b   Locke, Kelly ^b   Mitchell, Darren J ^a   Mouzon, Bernadette H ^b   Prinjha, Rab K ^a   Roberts, Andy D ^a   Sheppard, Robert J ^a   Watson, Robert J ^a   Bamborough, Paul ^b   more..

^a GLAXOSMITHKLINE   (United Kingdom)

^b GLAXOSMITHKLINE   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

2 (BENZYLOXY) 8 CHLORO 3 METHYL 1,7 NAPHTHYRIDINE; 2 CHLORO 3 METHYL 8 NITROQUINOLINE; 2 METHYL N,3 DIPHENYLACRYLAMIDE; 3 METHYL 8 (PIPERIDIN 4 YLAMINO) 1,7 NAPHTHYRIDIN 2(1H) ONE HYDROCHLORIDE; 3 METHYL 8 (PIPERIDIN 4 YLAMINO)QUINOLIN 2(1H) ONE; 3 METHYL 8 (PROPYLAMINO)QUINOLIN 2(1H) ONE; 3 METHYL 8 (PYRROLIDIN 3 YLAMINO) 1,7 NAPHTHYRIDINANDIN 2(1H) ONE; 3 METHYL 8 (PYRROLIDIN 3 YLAMINO)QUINOLIN 2(1H) ONE; 3 METHYL 8 (PYRROLIDIN-3 YLAMINO) 1,7 NAPHTHYRIDIN 2(1H) ONE; 3 METHYL 8 PYRROLIDIN 3 YLAMINO)QUINOLIN 2(1H) ONE; 3 METHYL 8 [(PIPERIDIN 4 YLMETHYL)AMINO] 1,7 NAPHTHYRIDIN 2 (1H) ONE; 3 METHYL 8 [[2 (PIPERIDIN 3 YL)ETHYL]AMINO] 1,7 NAPHTHYRIDIN 2(1H) ONE; 3 METHYL 8 [[2 (PIPERIDIN 4 YL)ETHYL]AMINO]1,7 NAPHTHYRIDIN 2(1H) ONE; 3 METHYLQUINOLIN 2(1H) ONE; 3 [(METHYL 2 OXO 1,2 DIHYDROQUINOLIN 8 YL)AMINO]PROPANOIC ACID; 8 AMINO 3 METHYLQUINOLIN 2(1H) ONE; 8 CHLORO 3 METHYL 1,7 NAPHTHYRIDIN 2(1H) ONE; 8 [(2 HYDROXYETHYL)AMINO] 3 METHYLQUINOLIN 2(1H ) ONE; 8 [(2 METHOXYETHYL)AMINO] 3 METHYLQUINOLIN 2(1H) ONE; 8 [(3 HYDROXYPROPYL)AMINO] 3 METHYLQUINOLIN 2(1H) ONE; 8 [[(1 IMIDAZOL 2 YL)METHYL]AMINO] 3 METHYLQUINOLIN 2(1H) ONE; 8 [[2 (DIMETHYLAMINO)ETHYL]AMINO] 3 METHYL 1,7 NAPHTHYRIDIN 2(1H) ONE; 8 [[2 (IMETHYLAMINO)ETHYL]AMINO] 3 METHYLQUINOLIN 2(1H) ONE; 8 [[3 (DIMETHYLAMINO) 2,2 DIMETHYLPROPYL]AMINO] 3 METHYL 1,7 NAPHTHYRIDIN 2(1H) ONE; 8 [[3 (DIMETHYLAMINO)PROPYL]AMINO] 3 METHYL 1,7 NAPHTHYRIDIN 2(1H) ONE; 8 [[3 (DIMETHYLAMINO)PROPYL]AMINO] 3 METHYLQUINOLIN 2(1H) ONE; ADENOSINE TRIPHOSPHATASE INHIBITOR; ADENOSINE TRIPHOSPHATE FAMILY AAA DOMAIN CONTAINING 2 BROMODOMAIN INHIBITOR; BROMODOMAIN INHIBITOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; ADENOSINE TRIPHOSPHATASE; ANTINEOPLASTIC AGENT; ENZYME INHIBITOR; QUINOLONE DERIVATIVE;

ARTICLE; BINDING AFFINITY; BINDING SITE; COMPETITIVE BINDING ASSAY; CRYSTAL STRUCTURE; DRUG BINDING; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; HYDROGEN BOND; HYDROPHILICITY; NUCLEAR MAGNETIC RESONANCE; PHYSICAL CHEMISTRY; SURFACE PLASMON RESONANCE; X RAY CRYSTALLOGRAPHY; AMINO ACID SEQUENCE; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DEVELOPMENT; METABOLISM; MOLECULAR GENETICS; PROTEIN TERTIARY STRUCTURE;

ADENOSINE TRIPHOSPHATASES; AMINO ACID SEQUENCE; ANTINEOPLASTIC AGENTS; DRUG DISCOVERY; ENZYME INHIBITORS; HUMANS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; PROTEIN STRUCTURE, TERTIARY; QUINOLONES;

EID: 84937960999     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.5b00772     Document Type: Article

References (54)

1. Caron, C.; Lestrat, C.; Marsal, S.; Escoffier, E.; Curtet, S.; Virolle, V.; Barbry, P.; Debernardi, A.; Brambilla, C.; Brambilla, E.; Rousseaux, S.; Khochbin, S. Functional characterization of ATAD2 as a new cancer/testis factor and a predictor of poor prognosis in breast and lung cancers Oncogene 2010, 29, 5171-5181
2. Duan, Z.; Zou, J. X.; Yang, P.; Wang, Y.; Borowsky, A. D.; Gao, A. C.; Chen, H. W. Developmental and androgenic regulation of chromatin regulators EZH2 and ANCCA/ATAD2 in the prostate Via MLL histone methylase complex Prostate 2013, 73, 455-466
3. Boussouar, F.; Jamshidikia, M.; Morozumi, Y.; Rousseaux, S.; Khochbin, S. Malignant genome reprogramming by ATAD2 Biochim. Biophys. Acta, Gene Regul. Mech. 2013, 1829, 1010-1014
4. Zou, J. X.; Revenko, A. S.; Li, L. B.; Gemo, A. T.; Chen, H. W. ANCCA, an estrogen-regulated AAA+ ATPase coactivator for ERalpha, is required for coregulator occupancy and chromatin modification Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 18067-18072
5. 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
6. Hsia, E. Y.; Kalashnikova, E. V.; Revenko, A. S.; Zou, J. X.; Borowsky, A. D.; Chen, H. W. Deregulated E2F and the AAA+ coregulator ANCCA drive proto-oncogene ACTR/AIB1 overexpression in breast cancer Mol. Cancer Res. 2010, 8, 183-193
7. 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
8. 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
9. Ciro, M.; Prosperini, E.; Quarto, M.; Grazini, U.; Walfridsson, J.; McBlane, F.; Nucifero, P.; Pacchiana, G.; Capra, M.; Christensen, J.; Helin, K. ATAD2 is a novel cofactor for MYC, overexpressed and amplified in aggressive tumors Cancer Res. 2009, 69, 8491-8498
10. Raeder, M. B.; Birkeland, E.; Trovik, J.; Krakstad, C.; Shehata, S.; Schumacher, S.; Zack, T. I.; Krohn, A.; Werner, H. M.; Moody, S. E.; Wik, E.; Stefansson, I. M.; Holst, F.; Oyan, A. M.; Tamayo, P.; Mesirov, J. P.; Kalland, K. H.; Akslen, L. A.; Simon, R.; Beroukhim, R.; Salvesen, H. B. Integrated genomic analysis of the 8q24 amplification in endometrial cancers identifies ATAD2 as essential to MYC-dependent cancers PLoS One 2013, 8, e54873
11. Wu, G.; Liu, H.; He, H.; Wang, Y.; Lu, X.; Yu, Y.; Xia, S.; Meng, X.; Liu, Y. miR-372 down-regulates the oncogene ATAD2 to influence hepatocellular carcinoma proliferation and metastasis BMC Cancer 2014, 14, 107
12. Wu, G.; Lu, X.; Wang, Y.; He, H.; Meng, X.; Xia, S.; Zhen, K.; Liu, Y. Epigenetic high regulation of ATAD2 regulates the Hh pathway in human hepatocellular carcinoma Int. J. Oncol. 2014, 45, 351-361
13. Fellenberg, J.; Bernd, L.; Delling, G.; Witte, D.; Zahlten-Hinguranage, A. Prognostic significance of drug-regulated genes in high-grade osteosarcoma Mod. Pathol. 2007, 20, 1085-1094
14. Fouret, R.; Laffaire, J.; Hofman, P.; Beau-Faller, M.; Mazieres, J.; Validire, P.; Girard, P.; Camilleri-Broet, S.; Vaylet, F.; Leroy-Ladurie, F.; Soria, J. C.; Fouret, P. A comparative and integrative approach identifies ATPase family, AAA domain containing 2 as a likely driver of cell proliferation in lung adenocarcinoma Clin. Cancer Res. 2012, 18, 5606-5616
15. Salhia, B.; Kiefer, J.; Ross, J. T.; Metapally, R.; Martinez, R. A.; Johnson, K. N.; DiPerna, D. M.; Paquette, K. M.; Jung, S.; Nasser, S.; Wallstrom, G.; Tembe, W.; Baker, A.; Carpten, J.; Resau, J.; Ryken, T.; Sibenaller, Z.; Petricoin, E. F.; Liotta, L. A.; Ramanathan, R. K.; Berens, M. E.; Tran, N. L. Integrated genomic and epigenomic analysis of breast cancer brain metastasis PLoS One 2014, 9, e85448
16. Leachman, N. T.; Brellier, F.; Ferralli, J.; Chiquet-Ehrismann, R.; Tucker, R. P. ATAD2B is a phylogenetically conserved nuclear protein expressed during neuronal differentiation and tumorigenesis Dev., Growth Differ. 2010, 52, 747-755
17. Nicodeme, E.; Jeffrey, K. L.; Schaefer, U.; Beinke, S.; Dewell, S.; Chung, C. W.; Chandwani, R.; Marazzi, I.; Wilson, P.; Coste, H.; White, J.; Kirilovsky, J.; Rice, C. M.; Lora, J. M.; Prinjha, R. K.; Lee, K.; Tarakhovsky, A. Suppression of inflammation by a synthetic histone mimic Nature 2010, 468, 1119-1123
18. Chung, C.; Coste, H.; White, J. H.; Mirguet, O.; Wilde, J.; Gosmini, R. L.; Delves, C.; Magny, S. M.; Woodward, R.; Hughes, S. A.; Boursier, E. V.; Flynn, H.; Bouillot, A. M.; Bamborough, P.; Brusq, J. M.; Gellibert, F. J.; Jones, E. J.; Riou, A. M.; Homes, P.; Martin, S. L.; Uings, I. J.; Toum, J.; Clement, C. A.; Boullay, A. B.; Grimley, R. L.; Blandel, F. M.; Prinjha, R. K.; Lee, K.; Kirilovsky, J.; Nicodeme, E. Discovery and characterization of small molecule inhibitors of the BET family bromodomains J. Med. Chem. 2011, 54, 3827-3838
19. 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, T. N.; French, C. A.; Wiest, O.; Kung, A. L.; Knapp, S.; Bradner, J. E. Selective inhibition of BET bromodomains Nature 2010, 468, 1067-1073
20. Gallenkamp, D.; Gelato, K. A.; Haendler, B.; Weinmann, H. Bromodomains and their pharmacological inhibitors ChemMedChem 2014, 9, 438-464
21. Garnier, J. M.; Sharp, P. P.; Burns, C. J. BET bromodomain inhibitors: a patent review Expert Opin. Ther. Pat. 2014, 24, 185-199
22. Chemical probes BAZ2-ICR, bromosporine, GSK2801, I-CBP112, and SGC-CBP30. http://www.thesgc.org/chemical-probes (accessed June 19, 2015).
23. 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
24. Drouin, L.; McGrath, S.; Vidler, L. R.; Chaikuad, A.; Monteiro, O.; Tallant, C.; Philpott, M.; Rogers, C.; Fedorov, O.; Liu, M.; Akhtar, W.; Hayes, A.; Raynaud, F.; Muller, S.; Knapp, S.; Hoelder, S. Structure enabled design of BAZ2-ICR, a chemical probe targeting the bromodomains of BAZ2A and BAZ2B J. Med. Chem. 2015, 58, 2553-2559
25. Chen, P.; Chaikuad, A.; Bamborough, P.; Bantscheff, M.; Bountra, C.; Chung, C. W.; Fedorov, O.; Grandi, P.; Jung, D.; Lesniak, R.; Lindon, M.; Muller, S.; Philpott, M.; Prinjha, R. K.; Rogers, C. M.; Selenski, C.; Tallant, C.; Werner, T.; Willson, T. M.; Knapp, S.; Drewry, D. H. Discovery and characterization of GSK2801, a selective chemical probe for the bromodomains BAZ2A and BAZ2B J. Med. Chem. 2015, DOI: 10.1021/acs.jmedchem.5b00209.
26. Theodoulou, N. H.; Bamborough, P.; Bannister, A. J.; Becher, I.; Bit, R. A.; Che, K. H.; Chung, C. W.; Dittmann, A.; Drewes, G.; Drewry, D. H.; Gordon, L.; Grandi, P.; Leveridge, M.; Lindon, M.; Michon, A. M.; Molnar, J.; Robson, S. C.; Tomkinson, N. C.; Kouzarides, T.; Prinjha, R. K.; Humphreys, P. G. The discovery of I-BRD9, a selective cell active chemical probe for bromodomain containing protein 9 inhibition. J. Med. Chem. 2015, DOI: 10.1021/acs.jmedchem.5b00256.
27. Clark, P. G.; Vieira, L. C.; Tallant, C.; Fedorov, O.; Singleton, D. C.; Rogers, C. M.; Monteiro, O. P.; Bennett, J. M.; Baronio, R.; Muller, S.; Daniels, D. L.; Mendez, J.; Knapp, S.; Brennan, P. E.; Dixon, D. J. LP99: discovery and synthesis of the first selective BRD7/9 bromodomain inhibitor Angew. Chem., Int. Ed. 2015, 54, 6217-6221
28. Demont, E. H.; Bamborough, P.; Chung, C. W.; Craggs, P. D.; Fallon, D.; Gordon, L. J.; Grandi, P.; Hobbs, C. I.; Hussain, J.; Jones, E. J.; Le, G. A.; Michon, A. M.; Mitchell, D. J.; Prinjha, R. K.; Roberts, A. D.; Sheppard, R. J.; Watson, R. J. 1,3-Dimethyl benzimidazolones are potent, selective inhibitors of the BRPF1 bromodomain ACS Med. Chem. Lett. 2014, 5, 1190-1195
29. Vidler, L. R.; Brown, N.; Knapp, S.; Hoelder, S. Druggability analysis and structural classification of bromodomain acetyl-lysine binding sites J. Med. Chem. 2012, 55, 7346-7359
30. Chaikuad, A.; Petros, A. M.; Fedorov, O.; Xu, J.; Knapp, S. Structure-based approaches towards identification of fragments for the low-druggability ATAD2 bromodomain MedChemComm 2014, 5, 1843-1848
31. Harner, M. J.; Chauder, B. A.; Phan, J.; Fesik, S. W. Fragment-based screening of the bromodomain of ATAD2 J. Med. Chem. 2014, 57, 9687-9692
32. Poncet-Montange, G.; Zhan, Y.; Bardenhagen, J. P.; Petrocchi, A.; Leo, E.; Shi, X.; Lee Iv, G. R.; Leonard, P. G.; Geck Do, M. K.; Cardozo, M. G.; Andersen, J. N.; Palmer, W. S.; Jones, P.; Ladbury, J. E. Observed bromodomain flexibility reveals histone peptide- and small molecule ligand-compatible forms of ATAD2A Biochem. J. 2015, 466, 337-346
33. Muller, S.; Knapp, S. Discovery of BET bromodomain inhibitors and their role in target validation Med. Chem. Commun. 2014, 5, 228-296
34. Chung, C.; Dean, A. W.; Woolven, J. M.; Bamborough, P. Fragment-based discovery of bromodomain inhibitors part 1: inhibitor binding modes and implications for lead discovery J. Med. Chem. 2012, 55, 576-586
35. Chaikuad, A.; Felletar, I.; Von Delft, F.; Arrowsmith, C.; Edwards, A. M.; Bountra, C.; Knapp, S. PDB entry 4quu. http://www.rcsb.org, released July 30, 2014.
36. Fish, P. V.; Filippakopoulos, P.; Bish, G.; Brennan, P. E.; Bunnage, M. E.; Cook, A. S.; Federov, O.; Gerstenberger, B. S.; Jones, H.; Knapp, S.; Marsden, B.; Nocka, K.; Owen, D. R.; Philpott, M.; Picaud, S.; Primiano, M. J.; Ralph, M. J.; Sciammetta, N.; Trzupek, J. D. Identification of a chemical probe for bromo and extra C-terminal bromodomain inhibition through optimization of a fragment-derived hit J. Med. Chem. 2012, 55, 9831-9837
37. Wu, J.; Shin, J.; Williams, C. M.; Geoghegan, K. F.; Wright, S. W.; Limburg, D. C.; Sahasrabudhe, P.; Bonin, P. D.; Lefker, B. A.; Ramsey, S. J. Design and chemoproteomic functional characterization of a chemical probe targeted to bromodomains of BET family proteins Med. Chem. Commun. 2014, 5, 1871-1878
38. Scott, J. P. Two-step synthesis of 3-aryl-1,3-dihydro-2 H -imidazo[4,5- b ]pyridin-2-ones Synlett 2006, 13, 2083-2086
39. Fan, W.; Haxell, T. F. N.; Jenks, M. G.; Kawanishi, N.; Lee, S.; Liu, H.; Malaska, M. J.; Moore, J. A.; Ogino, Y.; Onozaki, Y.; Pandi, B.; Peel, M. R.; Sakamoto, T.; Siu, T. Preparation of substituted fused naphthyridine derivatives as AKT inhibitors for treating cancer. WO2010104933A1, 2010.
40. Ember, S. W.; Zhu, J. Y.; Olesen, S. H.; Martin, M. P.; Becker, A.; Berndt, N.; Georg, G. I.; Schonbrunn, E. Acetyl-lysine binding site of bromodomain-containing protein 4 (BRD4) interacts with diverse kinase inhibitors ACS Chem. Biol. 2014, 9, 1160-1171
41. Seal, J.; Lamotte, Y.; Donche, F.; Bouillot, A.; Mirguet, O.; Gellibert, F.; Nicodeme, E.; Krysa, G.; Kirilovsky, J.; Beinke, S.; McCleary, S.; Rioja, I.; Bamborough, P.; Chung, C. W.; Gordon, L.; Lewis, T.; Walker, A. L.; Cutler, L.; Lugo, D.; Wilson, D. M.; Witherington, J.; Lee, K.; Prinjha, R. K. Identification of a novel series of BET family bromodomain inhibitors: binding mode and profile of I-BET151 (GSK1210151A) Bioorg. Med. Chem. Lett. 2012, 22, 2968-2972
42. Mirguet, O.; Gosmini, R.; Toum, J.; Clement, C. A.; Barnathan, M.; Brusq, J. M.; Mordaunt, J. E.; Grimes, R. M.; Crowe, M.; Pineau, O.; Ajakane, M.; Daugan, A.; Jeffrey, P.; Cutler, L.; Haynes, A. C.; Smithers, N. N.; Chung, C. W.; Bamborough, P.; Uings, I. J.; Lewis, A.; Witherington, J.; Parr, N.; Prinjha, R. K.; Nicodeme, E. Discovery of epigenetic regulator I-BET762: lead optimization to afford a clinical candidate inhibitor of the BET bromodomains J. Med. Chem. 2013, 56, 7501-7515
43. Otwinowski, Z.; Minor, W. Processing of X-ray diffraction data collected in oscillation mode Methods Enzymol.: Macromol. Crystallogr., Part A 1997, 276, 307-326
44. Leslie, A. G. W. Recent changes to the MOSFLM package for processing film and image plate data Jt. CCP4 ESF-EACBM Newsl. 1992, 26, 29-35
45. Kabsch, W. XDS Acta Crystallogr., Sect. D: Biol. Crystallogr. 2010, 66, 125-132
46. Evans, P. R. Data reduction Proc. CCP4 Study Weekend, Data Collect. Process. 1993, 114-122
47. Evans, P. R.; Murshudov, G. N. How good are my data and what is the resolution? Acta Crystallogr., Sect. D: Biol. Crystallogr. 2013, 69, 1204-1214
48. Collaborative Computational Project No.4. The CCP4 suite: programs for protein crystallography. Acta Crystallogr., Sect. D: Biol. Crystallogr. 1994, D50, 760-763.
49. Murshudov, G. N.; Vagin, A. A.; Dodson, E. J. Refinement of macromolecular structures by the maximum-likelihood method Acta Crystallogr., Sect. D: Biol. Crystallogr. 1997, 53, 240-255
50. Emsley, P.; Cowtan, K. Coot: model-building tools for molecular graphics Acta Crystallogr., D: Biol. Crystallogr. 2004, 60, 2126-2132
51. Dawson, M. A.; Prinjha, R. K.; Dittmann, A.; Giotopoulos, G.; Bantscheff, M.; Chan, W. I.; Robson, S. C.; Chung, C. W.; Hopf, C.; Savitski, M. M.; Huthmacher, C.; Gudgin, E.; Lugo, D.; Beinke, S.; Chapman, T. D.; Roberts, E. J.; Soden, P. E.; Auger, K. R.; Mirguet, O.; Doehner, K.; Delwel, R.; Burnett, A. K.; Jeffrey, P.; Drewes, G.; Lee, K.; Huntly, B. J.; Kouzarides, T. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia Nature 2011, 478, 529-533
52. Gosmini, R.; Nguyen, V. L.; Toum, J.; Simon, C.; Brusq, J. M.; Krysa, G.; Mirguet, O.; Riou-Eymard, A. M.; Boursier, E. V.; Trottet, L.; Bamborough, P.; Clark, H.; Chung, C. W.; Cutler, L.; Demont, E. H.; Kaur, R.; Lewis, A. J.; Schilling, M. B.; Soden, P. E.; Taylor, S.; Walker, A. L.; Walker, M. D.; Prinjha, R. K.; Nicodeme, E. The discovery of I-BET726 (GSK1324726A), a potent tetrahydroquinoline ApoA1 up-regulator and selective BET bromodomain inhibitor J. Med. Chem. 2014, 57, 8111-8131
53. Diaz, R.; Luengo-Arratta, S. A.; Seixas, J. D.; Amata, E.; Devine, W.; Cordon-Obras, C.; Rojas-Barros, D. I.; Jimenez, E.; Ortega, F.; Crouch, S. Identification and characterization of hundreds of potent and selective inhibitors of Trypanosoma brucei growth from a kinase-targeted library screening campaign PLoS Neglected Trop. Dis. 2014, 8, e3253
54. Trindade, A. F.; Gois, P. M.; Veiros, L. F.; Andr, V. +.; Duarte, M. T.; Afonso, C. A.; Caddick, S.; Cloke, F. G. Axial coordination of NHC ligands on dirhodium (II) complexes: generation of a new family of catalysts J. Org. Chem. 2008, 73, 4076-4086