Targeting BET Bromodomains in Cancer

Literature Cited

1. Aggarwal RR, Schweizer MT, Nanus DM, Pantuck AJ, Heath EI et al. 2020. A phase Ib/IIa study of the pan-BET inhibitor ZEN-3694 in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer. Clin. Cancer Res. 26:5338–47
   [Google Scholar]
2. Alamer E, Zhong C, Hajnik R, Soong L, Hu H. 2021. Modulation of BRD4 in HIV epigenetic regulation: implications for finding an HIV cure. Retrovirology 18:3
   [Google Scholar]
3. Ameratunga M, Brana I, Bono P, Postel-Vinay S, Plummer R et al. 2020. First-in-human phase 1 open label study of the BET inhibitor ODM-207 in patients with selected solid tumours. Br. J. Cancer 123:1730–36
   [Google Scholar]
4. Amorim S, Stathis A, Gleeson M, Iyengar S, Magarotto V et al. 2016. Bromodomain inhibitor OTX015 in patients with lymphoma or multiple myeloma: a dose-escalation, open-label, pharmacokinetic, phase 1 study. Lancet Haematol 3:e196–204
   [Google Scholar]
5. Asangani IA, Dommeti VL, Wang X, Malik R, Cieslik M et al. 2014. Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer. Nature 510:278–82
   [Google Scholar]
6. Aylott HE, Atkinson SJ, Bamborough P, Bassil A, Chung CW et al. 2021. Template-hopping approach leads to potent, selective, and highly soluble bromo and extraterminal domain (BET) second bromodomain (BD2) inhibitors. J. Med. Chem. 64:3249–81
   [Google Scholar]
7. Barabanshikova MV, Dubina IA, Lapin SV, Morozova EV, Vlasova JJ et al. 2017. Clinical correlates and prognostic significance of IL-8, sIL-2R, and immunoglobulin-free light chain levels in patients with myelofibrosis. Oncol. Res. Treat. 40:574–79
   [Google Scholar]
8. Belkina AC, Nikolajczyk BS, Denis GV. 2013. BET protein function is required for inflammation: Brd2 genetic disruption and BET inhibitor JQ1 impair mouse macrophage inflammatory responses. J. Immunol. 190:3670–78
   [Google Scholar]
9. Blake RA. 2019. GNE-0011, a novel monovalent BRD4 degrader. Cancer Res 79:13 Suppl.4452 (Abstr.)
   [Google Scholar]
10. Blum KA, Abramson J, Maris M, Flinn I, Goy A et al. 2018. A phase I study of CPI-0610, a bromodomain and extra terminal protein (BET) inhibitor in patients with relapsed or refractory lymphoma. Ann. Oncol. 29:iii7–9
    [Google Scholar]
11. Bolden JE, Tasdemir N, Dow LE, van Es JH, Wilkinson JE et al. 2014. Inducible in vivo silencing of Brd4 identifies potential toxicities of sustained BET protein inhibition. Cell Rep 8:1919–29
    [Google Scholar]
12. Bowry A, Kelly RDW, Petermann E. 2021. Hypertranscription and replication stress in cancer. Trends Cancer 7:9863–77
    [Google Scholar]
13. Bradbury RH, Callis R, Carr GR, Chen H, Clark E et al. 2016. Optimization of a series of bivalent triazolopyridazine based bromodomain and extraterminal inhibitors: the discovery of (3R)-4-[2-[4-[1-(3-Methoxy-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-4-piperidyl]phenoxy]ethyl]-1,3-dimethyl-piperazin-2-one (AZD5153). J. Med. Chem. 59:7801–17
    [Google Scholar]
14. Bui MH, Lin X, Albert DH, Li L, Lam LT et al. 2017. Preclinical characterization of BET family bromodo-main inhibitor ABBV-075 suggests combination therapeutic strategies. Cancer Res 77:2976–89
    [Google Scholar]
15. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO et al. 2012. The cBio Cancer Genomics Portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2:5401–4
    [Google Scholar]
16. Ceribelli M, Kelly PN, Shaffer AL, Wright GW, Xiao W et al. 2014. Blockade of oncogenic IκB kinase activity in diffuse large B-cell lymphoma by bromodomain and extraterminal domain protein inhibitors. PNAS 111:11365–70
    [Google Scholar]
17. Chapuy B, McKeown MR, Lin CY, Monti S, Roemer MG et al. 2013. Discovery and characterization of super-enhancer-associated dependencies in diffuse large B cell lymphoma. Cancer Cell 24:777–90
    [Google Scholar]
18. Cimas FJ, Niza E, Juan A, Noblejas-López MM, Bravo I et al. 2020. Controlled delivery of BET-PROTACs: in vitro evaluation of MZ1-loaded polymeric antibody conjugated nanoparticles in breast cancer. Pharmaceutics 12:10986
    [Google Scholar]
19. Cochran AG, Conery AR, Sims RJ 3rd 2019. Bromodomains: a new target class for drug development. Nat. Rev. Drug Discov. 18:609–28
    [Google Scholar]
20. Coleman DJ, Gao L, King CJ, Schwartzman J, Urrutia J et al. 2019. BET bromodomain inhibition blocks the function of a critical AR-independent master regulator network in lethal prostate cancer. Oncogene 38:5658–69
    [Google Scholar]
21. Crowe MD, Daugan AC-M, Gosmini RLM, Grimes RM, Mirguet O, Mordaunt JE. 2011. Condensed azepine derivatives as bromodomain inhibitors World Intellect. Prop. Org. Patent WO2011054844AI
22. Dai X, Gan W, Li X, Wang S, Zhang W et al. 2017. Prostate cancer-associated SPOP mutations confer resistance to BET inhibitors through stabilization of BRD4. Nat. Med. 23:1063–71
    [Google Scholar]
23. Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J et al. 2011. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 146:904–17
    [Google Scholar]
24. Ding N, Hah N, Yu RT, Sherman MH, Benner C et al. 2015. BRD4 is a novel therapeutic target for liver fibrosis. PNAS 112:15713–18
    [Google Scholar]
25. Doroshow DB, Eder JP, LoRusso PM. 2017. BET inhibitors: a novel epigenetic approach. Ann. Oncol. 28:1776–87
    [Google Scholar]
26. Dragovich PS, Pillow TH, Blake RA, Sadowsky JD, Adaligil E et al. 2021a. Antibody-mediated delivery of chimeric BRD4 degraders. Part 1: exploration of antibody linker, payload loading, and payload molecular properties. J. Med. Chem. 64:52534–75
    [Google Scholar]
27. Dragovich PS, Pillow TH, Blake RA, Sadowsky JD, Adaligil E et al. 2021b. Antibody-mediated delivery of chimeric BRD4 degraders. Part 2: improvement of in vitro antiproliferation activity and in vivo antitumor efficacy. J. Med. Chem. 64:52576–607
    [Google Scholar]
28. Eagen KP, French CA. 2021. Supercharging BRD4 with NUT in carcinoma. Oncogene 40:1396–408
    [Google Scholar]
29. Esteve-Arenys A, Valero JG, Chamorro-Jorganes A, Gonzalez D, Rodriguez V et al. 2018. The BET bromo-domain inhibitor CPI203 overcomes resistance to ABT-199 (venetoclax) by downregulation of BFL-1/A1 in in vitro and in vivo models of MYC+/BCL2+ double hit lymphoma. Oncogene 37:1830–44
    [Google Scholar]
30. Faivre EJ, McDaniel KF, Albert DH, Mantena SR, Plotnik JP et al. 2020. Selective inhibition of the BD2 bromodomain of BET proteins in prostate cancer. Nature 578:306–10
    [Google Scholar]
31. Falchook G, Rosen S, LoRusso P, Watts J, Gupta S et al. 2020. Development of 2 bromodomain and extraterminal inhibitors with distinct pharmacokinetic and pharmacodynamic profiles for the treatment of advanced malignancies. Clin. Cancer Res. 26:1247–57
    [Google Scholar]
32. Filippakopoulos P, Knapp S. 2014. Targeting bromodomains: epigenetic readers of lysine acetylation. Nat. Rev. Drug Discov. 13:337–56
    [Google Scholar]
33. Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert JP et al. 2012. Histone recognition and large-scale structural analysis of the human bromodomain family. Cell 149:214–31
    [Google Scholar]
34. Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB et al. 2010. Selective inhibition of BET bromodomains. Nature 468:1067–73
    [Google Scholar]
35. Fong CY, Gilan O, Lam EY, Rubin AF, Ftouni S et al. 2015. BET inhibitor resistance emerges from leukaemia stem cells. Nature 525:538–42
    [Google Scholar]
36. Gadd MS, Testa A, Lucas X, Chan KH, Chen W et al. 2017. Structural basis of PROTAC cooperative recognition for selective protein degradation. Nat. Chem. Biol. 13:514–21
    [Google Scholar]
37. Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B et al. 2013. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci. Signal. 6:269pl1
    [Google Scholar]
38. Gerlach D, Tontsch-Grunt U, Baum A, Popow J, Scharn D et al. 2018. The novel BET bromodomain inhibitor BI 894999 represses super-enhancer-associated transcription and synergizes with CDK9 inhibition in AML. Oncogene 37:2687–701
    [Google Scholar]
39. Gilan O, Rioja I, Knezevic K, Bell MJ, Yeung MM et al. 2020. Selective targeting of BD1 and BD2 of the BET proteins in cancer and immunoinflammation. Science 368:387–94
    [Google Scholar]
40. Gong F, Chiu LY, Miller KM. 2016. Acetylation reader proteins: linking acetylation signaling to genome maintenance and cancer. PLOS Genet 12:e1006272
    [Google Scholar]
41. Groves IJ, Sinclair JH, Wills MR. 2020. Bromodomain inhibitors as therapeutics for herpesvirus-related disease: All BETs are off?. Front. Cell. Infect. Microbiol. 10:329
    [Google Scholar]
42. Houzelstein D, Bullock SL, Lynch DE, Grigorieva EF, Wilson VA, Beddington RS 2002. Growth and early postimplantation defects in mice deficient for the bromodomain-containing protein Brd4. Mol. Cell. Biol. 22:3794–802
    [Google Scholar]
43. Janouskova H, El Tekle G, Bellini E, Udeshi ND, Rinaldi A et al. 2017. Opposing effects of cancer-type-specific SPOP mutants on BET protein degradation and sensitivity to BET inhibitors. Nat. Med. 23:1046–54
    [Google Scholar]
44. Jiang Q, Jamieson C. 2018. BET'ing on dual JAK/BET inhibition as a therapeutic strategy for myeloproliferative neoplasms. Cancer Cell 33:3–5
    [Google Scholar]
45. Jin X, Yan Y, Wang D, Ding D, Ma T et al. 2018. DUB3 promotes BET inhibitor resistance and cancer progression by deubiquitinating BRD4. Mol. Cell 71:592–605.e4
    [Google Scholar]
46. Keller PCJ, Mertz J, Salama M, Zavidij O, Verstovsek S et al. 2021. BET inhibitor pelabresib decreases inflammatory cytokines, improves bone marrow fibrosis and function, and demonstrates clinical response irrespective of mutation status in myelofibrosis patients Poster presented at EHA 2021 Virtual Congress Online, June 9, Abstr. EP1080
47. Kerscher B, Barlow JL, Rana BM, Jolin HE, Gogoi M et al. 2019. BET bromodomain inhibitor iBET151 impedes human ILC2 activation and prevents experimental allergic lung inflammation. Front. Immunol. 10:678
    [Google Scholar]
48. Kleppe M, Koche R, Zou L, van Galen P, Hill CE et al. 2018. Dual targeting of oncogenic activation and inflammatory signaling increases therapeutic efficacy in myeloproliferative neoplasms. Cancer Cell 33:785–87
    [Google Scholar]
49. Kremyanskaya MMJ, Patriarca A, Gupta V, Devos T, Harrison C et al. 2021. Clinical benefit of pelabresib (CPI-0610) in combination with ruxolitinib in JAK inhibitor treatment naïve myelofibrosis patients: interim efficacy subgroup analysis from arm 3 of MANIFEST PH2 study Poster presented at EHA 2021 Virtual Congress, Online June 9, Abstr. EP1085
50. Kurimchak AM, Shelton C, Duncan KE, Johnson KJ, Brown J et al. 2016. Resistance to BET bromodomain inhibitors is mediated by kinome reprogramming in ovarian cancer. Cell Rep 16:1273–86
    [Google Scholar]
51. LeRoy G, Rickards B, Flint SJ 2008. The double bromodomain proteins Brd2 and Brd3 couple histone acetylation to transcription. Mol. Cell 30:51–60
    [Google Scholar]
52. Lewin J, Soria JC, Stathis A, Delord JP, Peters S et al. 2018. Phase Ib trial with birabresib, a small-molecule inhibitor of bromodomain and extraterminal proteins, in patients with selected advanced solid tumors. J. Clin. Oncol. 36:3007–14
    [Google Scholar]
53. Lihou C, Zhou G, Zheng F. 2020. A phase 1 study of INCB057643 monotherapy in patients with relapsed or refractory myelofibrosis (INCB 57643–103). Blood 136:16–17
    [Google Scholar]
54. Liu Z, Chen H, Wang P, Li Y, Wold EA et al. 2020. Discovery of orally bioavailable chromone derivatives as potent and selective BRD4 inhibitors: scaffold hopping, optimization, and pharmacological evaluation. J. Med. Chem. 63:5242–56
    [Google Scholar]
55. Liu Z, Tian B, Chen H, Wang P, Brasier AR, Zhou J. 2018. Discovery of potent and selective BRD4 inhibitors capable of blocking TLR3-induced acute airway inflammation. Eur. J. Med. Chem. 151:450–61
    [Google Scholar]
56. Liu Z, Wang P, Chen H, Wold EA, Tian B et al. 2017. Drug discovery targeting bromodomain-containing protein 4. J. Med. Chem. 60:4533–58
    [Google Scholar]
57. Loven J, Hoke HA, Lin CY, Lau A, Orlando DA et al. 2013. Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell 153:320–34
    [Google Scholar]
58. Ma Y, Wang L, Neitzel LR, Loganathan SN, Tang N et al. 2017. The MAPK pathway regulates intrinsic resistance to BET inhibitors in colorectal cancer. Clin. Cancer Res. 23:2027–37
    [Google Scholar]
59. Mascarenhas J, Harrison C, Luptakova K, Christo J, Wang J et al. 2020a. MANIFEST-2, a global, phase 3, randomized, double-blind, active-control study of CPI-0610 and ruxolitinib versus placebo and ruxolitinib in JAK-inhibitor-naive myelofibrosis patients. Blood 136:Suppl. 143
    [Google Scholar]
60. Mascarenhas J, Harrison C, Patriarca A, Devos T, Palandri F et al. 2020b. CPI-0610, a bromodomain and extraterminal domain protein (BET) inhibitor, in combination with ruxolitinib, in JAK inhibitor treatment naïve myelofibrosis patients: update from MANIFEST phase 2 study Poster presented at EHA 2021 Virtual Congress, Online June 12, Abstr. EP108
61. Mascarenhas J, Harrison C, Patriarca A, Devos T, Palandri F et al. 2020c. CPI-0610, a bromodomain and extraterminal domain protein (BET) inhibitor, in combination with ruxolitinib, in JAK-inhibitor-naïve myelofibrosis patients: update of MANIFEST phase 2 study Poster presented at 62nd ASH Annual Meeting and Exposition, Online Dec. 5
62. Mascarenhas J, Kremyanskaya M, Hoffman R, Bose P, Talpaz M et al. 2019. MANIFEST, a phase 2 study of CPI-0610, a bromodomain and extraterminal domain inhibitor (BETi), as monotherapy or “add-on” to ruxolitinib, in patients with refractory or intolerant advanced myelofibrosis. Blood 134:(Suppl. 1)670
    [Google Scholar]
63. McDaniel KF, Wang L, Soltwedel T, Fidanze SD, Hasvold LA et al. 2017. Discovery of N-(4-(2,4-Difluorophenoxy)-3-(6-methyl-7-oxo-6,7-dihydro-1 H-pyrrolo[2,3-c]pyridin-4-yl)phenyl) ethanesulfonamide (ABBV-075/mivebresib), a potent and orally available bromodomain and extraterminal domain (BET) family bromodomain inhibitor. J. Med. Chem. 60:8369–84
    [Google Scholar]
64. Mertz JA, Conery AR, Bryant BM, Sandy P, Balasubramanian S et al. 2011. Targeting MYC dependence in cancer by inhibiting BET bromodomains. PNAS 108:16669–74
    [Google Scholar]
65. Mertz JA, Keller PJ, Meyer RD, Zavidij O, Cui J et al. 2020. The BET inhibitor, CPI-0610, promotes myeloid differentiation in myelofibrosis patient bone marrow and peripheral CD34+ hematopoietic stem cells. Blood 136:37–38
    [Google Scholar]
66. Mills RJ, Humphrey SJ, Fortuna PRJ, Lor M, Foster SR et al. 2021. BET inhibition blocks inflammation-induced cardiac dysfunction and SARS-CoV-2 infection. Cell 184:2167–82.e22
    [Google Scholar]
67. Miyoshi S, Ooike S, Iwata K, Hikawa H, Sugahara K. 2009. Antitumor agent World Intellect. Prop. Org. Patent WO2009084693A1
68. Mujtaba S, Zeng L, Zhou MM. 2007. Structure and acetyl-lysine recognition of the bromodomain. Oncogene 26:5521–27
    [Google Scholar]
69. Nicodeme E, Jeffrey KL, Schaefer U, Beinke S, Dewell S et al. 2010. Suppression of inflammation by a synthetic histone mimic. Nature 468:1119–23
    [Google Scholar]
70. Nowak RP, DeAngelo SL, Buckley D, He Z, Donovan KA et al. 2018. Plasticity in binding confers selectivity in ligand-induced protein degradation. Nat. Chem. Biol. 14:706–14
    [Google Scholar]
71. Ntranos A, Casaccia P. 2016. Bromodomains: translating the words of lysine acetylation into myelin injury and repair. Neurosci. Lett. 625:4–10
    [Google Scholar]
72. Olp MD, Sprague DJ, Goetz CJ, Kathman SG, Wynia-Smith SL et al. 2020. Covalent-fragment screening of BRD4 identifies a ligandable site orthogonal to the acetyl-lysine binding sites. ACS Chem. Biol. 15:1036–49
    [Google Scholar]
73. Ouyang L, Zhang L, Liu J, Fu L, Yao D et al. 2017. Discovery of a small-molecule bromodomain-containing protein 4 (BRD4) inhibitor that induces AMP-activated protein kinase-modulated autophagy-associated cell death in breast cancer. J. Med. Chem. 60:9990–10012
    [Google Scholar]
74. Petretich M, Demont EH, Grandi P. 2020. Domain-selective targeting of BET proteins in cancer and immunological diseases. Curr. Opin. Chem. Biol. 57:184–93
    [Google Scholar]
75. Pettit K, Odenike O. 2017. Novel therapies for myelofibrosis. Curr. Hematol. Malig. Rep. 12:611–24
    [Google Scholar]
76. Piha-Paul SA, Hann CL, French CA, Cousin S, Brana I et al. 2020. Phase 1 study of molibresib (GSK525762), a bromodomain and extra-terminal domain protein inhibitor, in NUT carcinoma and other solid tumors. JNCI Cancer Spectr 4:pkz093
    [Google Scholar]
77. Pillow TH, Adhikari P, Blake RA, Chen J, Del Rosario G et al. 2020. Antibody conjugation of a chimeric BET degrader enables invivo activity. ChemMedChem 15:117–25
    [Google Scholar]
78. Postel-Vinay S, Herbschleb K, Massard C, Woodcock V, Soria JC et al. 2019. First-in-human phase I study of the bromodomain and extraterminal motif inhibitor BAY 1238097: emerging pharmacokinetic/pharmacodynamic relationship and early termination due to unexpected toxicity. Eur. J. Cancer 109:103–10
    [Google Scholar]
79. Preston A, Atkinson SJ, Bamborough P, Chung CW, Craggs PD et al. 2020a. Design and synthesis of a highly selective and in vivo-capable inhibitor of the second bromodomain of the bromodomain and extra terminal domain family of proteins. J. Med. Chem. 63:9070–92
    [Google Scholar]
80. Preston A, Atkinson SJ, Bamborough P, Chung CW, Gordon LJ et al. 2020b. GSK973 is an inhibitor of the second bromodomains (BD2s) of the bromodomain and extra-terminal (BET) family. ACS Med. Chem. Lett. 11:1581–87
    [Google Scholar]
81. Qin C, Hu Y, Zhou B, Fernandez-Salas E, Yang CY et al. 2018. Discovery of QCA570 as an exceptionally potent and efficacious proteolysis targeting chimera (PROTAC) degrader of the bromodomain and extra-terminal (BET) proteins capable of inducing complete and durable tumor regression. J. Med. Chem. 61:6685–704
    [Google Scholar]
82. Raina K, Lu J, Qian Y, Altieri M, Gordon D et al. 2016. PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer. PNAS 113:7124–29
    [Google Scholar]
83. Rathert P, Roth M, Neumann T, Muerdter F, Roe JS et al. 2015. Transcriptional plasticity promotes primary and acquired resistance to BET inhibition. Nature 525:543–47
    [Google Scholar]
84. Ray KK, Nicholls SJ, Ginsberg HD, Johansson JO, Kalantar-Zadeh K et al. 2019. Effect of selective BET protein inhibitor apabetalone on cardiovascular outcomes in patients with acute coronary syndrome and diabetes: rationale, design, and baseline characteristics of the BETonMACE trial. Am. Heart J. 217:72–83
    [Google Scholar]
85. Sanchez R, Zhou MM. 2009. The role of human bromodomains in chromatin biology and gene transcription. Curr. Opin. Drug Discov. Devel. 12:659–65
    [Google Scholar]
86. Schwartz GG, Nicholls SJ, Toth PP, Sweeney M, Halliday C et al. 2021. Relation of insulin treatment for type 2 diabetes to the risk of major adverse cardiovascular events after acute coronary syndrome: an analysis of the BETonMACE randomized clinical trial. Cardiovasc. Diabetol. 20:125
    [Google Scholar]
87. Seton-Rogers S. 2014. Prostate cancer: BETting on epigenetic therapy. Nat. Rev. Cancer 14:384–85
    [Google Scholar]
88. Shah N, Wang P, Wongvipat J, Karthaus WR, Abida W et al. 2017. Regulation of the glucocorticoid receptor via a BET-dependent enhancer drives antiandrogen resistance in prostate cancer. eLife 6:e27861
    [Google Scholar]
89. Shang E, Wang X, Wen D, Greenberg DA, Wolgemuth DJ. 2009. Double bromodomain-containing gene Brd2 is essential for embryonic development in mouse. Dev. Dyn. 238:908–17
    [Google Scholar]
90. Sheppard GS, Wang L, Fidanze SD, Hasvold LA, Liu D et al. 2020. Discovery of N-Ethyl-4-[2-(4-fluoro-2,6-dimethyl-phenoxy)-5-(1-hydroxy-1-methyl-ethyl)phenyl]-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (ABBV-744), a BET bromodomain inhibitor with selectivity for the second bromodomain. J. Med. Chem. 63:5585–623
    [Google Scholar]
91. Shorstova T, Foulkes WD, Witcher M. 2021. Achieving clinical success with BET inhibitors as anti-cancer agents. Br. J. Cancer 124:1478–90
    [Google Scholar]
92. Shu S, Lin CY, He HH, Witwicki RM, Tabassum DP et al. 2016. Response and resistance to BET bromo-domain inhibitors in triple-negative breast cancer. Nature 529:413–17
    [Google Scholar]
93. Shu S, Wu HJ, Ge JY, Zeid R, Harris IS et al. 2020. Synthetic lethal and resistance interactions with BET bromodomain inhibitors in triple-negative breast cancer. Mol. Cell 78:1096–113.e8
    [Google Scholar]
94. Slavish PJ, Chi L, Yun MK, Tsurkan L, Martinez NE et al. 2020. Bromodomain-selective BET inhibitors are potent antitumor agents against MYC-driven pediatric cancer. Cancer Res 80:3507–18
    [Google Scholar]
95. Stahl M, Zeidan AM. 2017. Management of myelofibrosis: JAK inhibition and beyond. Expert Rev. Hematol. 10:459–77
    [Google Scholar]
96. Stathis A, Zucca E, Bekradda M, Gomez-Roca C, Delord JP et al. 2016. Clinical response of carcinomas harboring the BRD4-NUT oncoprotein to the targeted bromodomain inhibitor OTX015/MK-8628. Cancer Discov 6:492–500
    [Google Scholar]
97. Stratton MS, Haldar SM, McKinsey TA. 2017. BRD4 inhibition for the treatment of pathological organ fibrosis. F1000Research 6:1015
    [Google Scholar]
98. Su A, Ling F, Vaganay C, Sodaro G, Benaksas C et al. 2020. The folate cycle enzyme MTHFR is a critical regulator of cell response to MYC-targeting therapies. Cancer Discov 10:1894–911
    [Google Scholar]
99. Sun Y, Han J, Wang Z, Li X, Sun Y, Hu Z 2021. Safety and efficacy of bromodomain and extra-terminal inhibitors for the treatment of hematological malignancies and solid tumors: a systematic study of clinical trials. Front. Pharmacol. 11:621093
    [Google Scholar]
100. Talpaz MRR, Verstovsek S, Harrison C, Drummond M, Kiladjian J-J et al. 2020. CPI-0610, a bromodomain and extraterminal domain protein (BET) inhibitor, as monotherapy in advanced myelofibrosis patients refractory/intolerant to JAK inhibitor: update from phase 2 MANIFEST study Poster presented at 62nd ASH Annual Meeting and Exposition, Online Dec. 6
101. Tanaka M, Roberts JM, Seo HS, Souza A, Paulk J et al. 2016. Design and characterization of bivalent BET inhibitors. Nat. Chem. Biol. 12:1089–96
     [Google Scholar]
102. Tang P, Zhang J, Liu J, Chiang CM, Ouyang L. 2021. Targeting bromodomain and extraterminal proteins for drug discovery: from current progress to technological development. J. Med. Chem. 64:2419–35
     [Google Scholar]
103. Taniguchi Y. 2016. The bromodomain and extra-terminal domain (BET) family: functional anatomy of BET paralogous proteins. Int. J. Mol. Sci. 17:111849
     [Google Scholar]
104. Tefferi A, Vaidya R, Caramazza D, Finke C, Lasho T, Pardanani A 2011. Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profiling study. J. Clin. Oncol. 29:1356–63
     [Google Scholar]
105. Tian B, Liu Z, Yang J, Sun H, Zhao Y et al. 2018. Selective antagonists of the bronchiolar epithelial NF-κB-bromodomain-containing protein 4 pathway in viral-induced airway inflammation. Cell Rep 23:1138–51
     [Google Scholar]
106. Tian B, Yang J, Zhao Y, Ivanciuc T, Sun H et al. 2017. BRD4 couples NF-κB/RelA with airway inflammation and the IRF-RIG-I amplification loop in respiratory syncytial virus infection. J. Virol. 91:e00007-17
     [Google Scholar]
107. Tough DF, Tak PP, Tarakhovsky A, Prinjha RK 2016. Epigenetic drug discovery: breaking through the immune barrier. Nat. Rev. Drug Discov. 15:835–53
     [Google Scholar]
108. Toyoshima M, Howie HL, Imakura M, Walsh RM, Annis JE et al. 2012. Functional genomics identifies therapeutic targets for MYC-driven cancer. PNAS 109:9545–50
     [Google Scholar]
109. Tremblay D, Yacoub A, Hoffman R 2021. Overview of myeloproliferative neoplasms: history, pathogenesis, diagnostic criteria, and complications. Hematol. Oncol. Clin. North Am. 35:159–76
     [Google Scholar]
110. Tyler DS, Vappiani J, Caneque T, Lam EYN, Ward A et al. 2017. Click chemistry enables preclinical evaluation of targeted epigenetic therapies. Science 356:1397–401
     [Google Scholar]
111. Verstovsek SKM, Mascarenhas J, Talpaz M, Harrison C, Rampal R et al. 2021. Pelabresib (CPI-0610) improved anemia associated with myelofibrosis: interim results from MANIFEST phase 2 study Poster presented at EHA 2021 Virtual Congress, Online June 9, Abstr. EP1077
112. Waring MJ, Chen H, Rabow AA, Walker G, Bobby R et al. 2016. Potent and selective bivalent inhibitors of BET bromodomains. Nat. Chem. Biol. 12:1097–104
     [Google Scholar]
113. Watson RJ, Bamborough P, Barnett H, Chung CW, Davis R et al. 2020. GSK789: a selective inhibitor of the first bromodomains (BD1) of the bromo and extra terminal domain (BET) proteins. J. Med. Chem. 63:9045–69
     [Google Scholar]
114. Wellaway CR, Bamborough P, Bernard SG, Chung CW, Craggs PD et al. 2020. Structure-based design of a bromodomain and extraterminal domain (BET) inhibitor selective for the N-terminal bromodomains that retains an anti-inflammatory and antiproliferative phenotype. J. Med. Chem. 63:9020–44
     [Google Scholar]
115. Welti J, Sharp A, Yuan W, Dolling D, Nava Rodrigues D et al. 2018. Targeting bromodomain and extra-terminal (BET) family proteins in castration-resistant prostate cancer (CRPC). Clin. Cancer Res. 24:3149–62
     [Google Scholar]
116. Wienerroither S, Rauch I, Rosebrock F, Jamieson AM, Bradner J et al. 2014. Regulation of NO synthesis, local inflammation, and innate immunity to pathogens by BET family proteins. Mol. Cell. Biol. 34:415–27
     [Google Scholar]
117. Wyspianska BS, Bannister AJ, Barbieri I, Nangalia J, Godfrey A et al. 2014. BET protein inhibition shows efficacy against JAK2V617F-driven neoplasms. Leukemia 28:88–97
     [Google Scholar]
118. Xu Y, Vakoc CR. 2017. Targeting cancer cells with BET bromodomain inhibitors. Cold Spring Harb. Perspect. Med. 7:a026674
     [Google Scholar]
119. Yang Y, Wu Z, Chen P, Zheng P, Zhang H, Zhou J. 2020. Proteolysis-targeting chimeras mediate the degradation of bromodomain and extra-terminal domain proteins. Future Med. Chem. 12:1669–83
     [Google Scholar]
120. Zengerle M, Chan KH, Ciulli A. 2015. Selective small molecule induced degradation of the BET bromodomain protein BRD4. ACS Chem. Biol. 10:1770–77
     [Google Scholar]
121. Zhang P, Wang D, Zhao Y, Ren S, Gao K et al. 2017. Intrinsic BET inhibitor resistance in SPOP-mutated prostate cancer is mediated by BET protein stabilization and AKT-mTORC1 activation. Nat. Med. 23:1055–62
     [Google Scholar]
122. Zhao Y, Liu Q, Acharya P, Stengel KR, Sheng Q et al. 2016. High-resolution mapping of RNA polymerases identifies mechanisms of sensitivity and resistance to BET inhibitors in t(8;21) AML.. Cell Rep 16:2003–16
     [Google Scholar]
123. Zuber J, Shi J, Wang E, Rappaport AR, Herrmann H et al. 2011. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature 478:524–28
     [Google Scholar]