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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Recent Advances in the Development of CBP/p300 Bromodomain Inhibitors

Author(s): Ying Xiong, Mingming Zhang* and Yingxia Li*

Volume 27 , Issue 33 , 2020

Page: [5583 - 5598] Pages: 16

DOI: 10.2174/0929867326666190731141055

Price: $65


CBP and p300 are two closely related Histone Acetyltransferases (HATs) that interact with numerous transcription factors and act to increase the expression of their target genes. Both proteins contain a bromodomain flanking the HAT catalytic domain that is important in binding of CBP/p300 to chromatin, which offers an opportunity to develop protein-protein interaction inhibitors. Since their discovery in 2006, CBP/p300 bromodomains have attracted much interest as promising new epigenetic targets for diverse human diseases, including inflammation, cancer, autoimmune disorders, and cardiovascular disease. Herein, we present a comprehensive review of the structure, function, and inhibitors of CBP/p300 bromodomains developed in the last several years, which is expected to be beneficial to relevant studies.

Keywords: CBP/p300, bromodomain, histone acetyltransferases, genes, inhibitors, drug discovery.

Ali, I.; Conrad, R.J.; Verdin, E.; Ott, M. Lysine acetylation goes global: from epigenetics to metabolism and therapeutics. Chem. Rev., 2018, 118(3), 1216-1252.
[] [PMID: 29405707]
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(5942), 834-840.
[] [PMID: 19608861]
Mahalingam, D.; Medina, E.C.; Esquivel, J.A., II; Espitia, C.M.; Smith, S.; Oberheu, K.; Swords, R.; Kelly, K.R.; Mita, M.M.; Mita, A.C.; Carew, J.S.; Giles, F.J.; Nawrocki, S.T. Vorinostat enhances the activity of temsirolimus in renal cell carcinoma through suppression of survivin levels. Clin. Cancer Res., 2010, 16(1), 141-153.
[] [PMID: 20028765]
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(7180), 846-850.
[] [PMID: 18273021]
Xing, S.; Poirier, Y. The protein acetylome and the regulation of metabolism. Trends Plant Sci., 2012, 17(7), 423-430.
[] [PMID: 22503580]
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(36), 33721-33729.
[] [PMID: 11445580]
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 Discov. Today, 2014, 19(5), 654-660.
[] [PMID: 24269836]
Wang, X.; Moore, S.C.; Laszckzak, M.; Ausió, J. Acetylation increases the alpha-helical content of the histone tails of the nucleosome. J. Biol. Chem., 2000, 275(45), 35013-35020.
[] [PMID: 10938086]
Galvani, A.; Thiriet, C. Nucleosome dancing at the tempo of histone tail acetylation. Genes (Basel), 2015, 6(3), 607-621.
[] [PMID: 26184324]
Yee, S.P.; Branton, P.E. Detection of cellular proteins associated with human adenovirus type 5 early region 1A polypeptides. Virology, 1985, 147(1), 142-153.
[] [PMID: 2932846]
Eckner, R.; Ewen, M.E.; Newsome, D.; Gerdes, M.; DeCaprio, J.A.; Lawrence, J.B.; Livingston, D.M. Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor. Genes Dev., 1994, 8(8), 869-884.
[] [PMID: 7523245]
Chrivia, J.C.; Kwok, R.P.S.; Lamb, N.; Hagiwara, M.; Montminy, M.R.; Goodman, R.H. Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature, 1993, 365(6449), 855-859.
[] [PMID: 8413673]
Bannister, A.J.; Kouzarides, T. The CBP co-activator is a histone acetyltransferase. Nature, 1996, 384(6610), 641-643.
[] [PMID: 8967953]
Chan, H.M.; La Thangue, N.B. p300/CBP proteins: HATs for transcriptional bridges and scaffolds. J. Cell Sci., 2001, 114(Pt 13), 2363-2373.
[PMID: 11559745]
Wang, F.; Marshall, C.B.; Ikura, M. Transcriptional/epigenetic regulator CBP/p300 in tumorigenesis: structural and functional versatility in target recognition. Cell. Mol. Life Sci., 2013, 70(21), 3989-4008.
[] [PMID: 23307074]
Kalkhoven, E. CBP and p300: HATs for different occasions. Biochem. Pharmacol., 2004, 68(6), 1145-1155.
[] [PMID: 15313412]
Sauer, M.; Schuldner, M.; Hoffmann, N.; Cetintas, A.; Reiners, K.S.; Shatnyeva, O.; Hallek, M.; Hansen, H.P.; Gasser, S.; von Strandmann, E.P. CBP/p300 acetyltransferases regulate the expression of NKG2D ligands on tumor cells. Oncogene, 2017, 36(7), 933-941.
[] [PMID: 27477692]
Ghosh, S.; Taylor, A.; Chin, M.; Huang, H.R.; Conery, A.R.; Mertz, J.A.; Salmeron, A.; Dakle, P.J.; Mele, D.; Cote, A.; Jayaram, H.; Setser, J.W.; Poy, F.; Hatzivassiliou, G.; DeAlmeida-Nagata, D.; Sandy, P.; Hatton, C.; Romero, F.A.; Chiang, E.; Reimer, T.; Crawford, T.; Pardo, E.; Watson, V.G.; Tsui, V.; Cochran, A.G.; Zawadzke, L.; Harmange, J.C.; Audia, J.E.; Bryant, B.M.; Cummings, R.T.; Magnuson, S.R.; Grogan, J.L.; Bellon, S.F.; Albrecht, B.K.; Sims, R.J., III; Lora, J.M.; Regulatory, T. Regulatory T cell modulation by CBP/EP300 bromodomain inhibition. J. Biol. Chem., 2016, 291(25), 13014-13027.
[] [PMID: 27056325]
Gu, W.; Roeder, R.G. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell, 1997, 90(4), 595-606.
[] [PMID: 9288740]
Liu, L.; Scolnick, D.M.; Trievel, R.C.; Zhang, H.B.; Marmorstein, R.; Halazonetis, T.D.; Berger, S.L. p53 sites acetylated in vitro by PCAF and p300 are acetylated in vivo in response to DNA damage. Mol. Cell. Biol., 1999, 19(2), 1202-1209.
[] [PMID: 9891054]
Bouchal, J.; Santer, F.R.; Höschele, P.P.; Tomastikova, E.; Neuwirt, H.; Culig, Z. Transcriptional coactivators p300 and CBP stimulate estrogen receptor-beta signaling and regulate cellular events in prostate cancer. Prostate, 2011, 71(4), 431-437.
[] [PMID: 20859991]
Iyer, N.G.; Ozdag, H.; Caldas, C. p300/CBP and cancer. Oncogene, 2004, 23(24), 4225-4231.
[] [PMID: 15156177]
Gajer, J.M.; Furdas, S.D.; Gründer, 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(2)e137
[] [PMID: 25664930]
Di Cerbo, V.; Schneider, R. Cancers with wrong HATs: the impact of acetylation. Brief. Funct. Genomics, 2013, 12(3), 231-243.
[] [PMID: 23325510]
Demetriadou, C.; Kirmizis, A. Histone acetyltransferases in cancer: guardians or hazards? Crit. Rev. Oncog., 2017, 22(3-4), 195-218.
[] [PMID: 29604899]
Diab, A.; Zickl, L.; Abdel-Wahab, O.; Jhanwar, S.; Gulam, M.A.; Panageas, K.S.; Patel, J.P.; Jurcic, J.; Maslak, P.; Paietta, E.; Mangan, J.K.; Carroll, M.; Fernandez, H.F.; Teruya-Feldstein, J.; Luger, S.M.; Douer, D.; Litzow, M.R.; Lazarus, H.M.; Rowe, J.M.; Levine, R.L.; Tallman, M.S. Acute myeloid leukemia with translocation t(8;16) presents with features which mimic acute promyelocytic leukemia and is associated with poor prognosis. Leuk. Res., 2013, 37(1), 32-36.
[] [PMID: 23102703]
Wang, G.G.; Allis, C.D.; Chi, P. Chromatin remodeling and cancer, part I: covalent histone modifications. Trends Mol. Med., 2007, 13(9), 363-372.
[] [PMID: 17822958]
Xiao, X.S.; Cai, M.Y.; Chen, J.W.; Guan, X.Y.; Kung, H.F.; Zeng, Y.X.; Xie, D. High expression of p300 in human breast cancer correlates with tumor recurrence and predicts adverse prognosis. Chin. J. Cancer Res., 2011, 23(3), 201-207.
[] [PMID: 23467396]
Santer, F.R.; Höschele, P.P.; Oh, S.J.; Erb, H.H.; Bouchal, J.; Cavarretta, I.T.; Parson, W.; Meyers, D.J.; Cole, P.A.; Culig, Z. Inhibition of the acetyltransferases p300 and CBP reveals a targetable function for p300 in the survival and invasion pathways of prostate cancer cell lines. Mol. Cancer Ther., 2011, 10(9), 1644-1655.
[] [PMID: 21709130]
Dutta, R.; Tiu, B.; Sakamoto, K.M. CBP/p300 acetyltransferase activity in hematologic malignancies. Mol. Genet. Metab., 2016, 119(1-2), 37-43.
[] [PMID: 27380996]
Lasko, L.M.; Jakob, C.G.; Edalji, R.P.; Qiu, W.; Montgomery, D.; Digiammarino, E.L.; Hansen, T.M.; Risi, R.M.; Frey, R.; Manaves, V.; Shaw, B.; Algire, M.; Hessler, P.; Lam, L.T.; Uziel, T.; Faivre, E.; Ferguson, D.; Buchanan, F.G.; Martin, R.L.; Torrent, M.; Chiang, G.G.; Karukurichi, K.; Langston, J.W.; Weinert, B.T.; Choudhary, C.; de Vries, P.; Van Drie, J.H.; McElligott, D.; Kesicki, E.; Marmorstein, R.; Sun, C.; Cole, P.A.; Rosenberg, S.H.; Michaelides, M.R.; Lai, A.; Bromberg, K.D. Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours. Nature, 2017, 550(7674), 128-132.
[] [PMID: 28953875]
Iqbal, M.; Guimei, T.; Daiqing, L. Abstract 4132: roles of the acetyltransferases CBP/p300 in breast cancer. Cancer Res., 2017, 77(13)
Bosic, M.M.; Brasanac, D.C.; Stojkovic-Filipovic, J.M.; Zaletel, I.V.; Gardner, J.M.; Cirovic, S.L. Expression of p300 and p300/CBP associated factor (PCAF) in actinic keratosis and squamous cell carcinoma of the skin. Exp. Mol. Pathol., 2016, 100(3), 378-385.
[] [PMID: 27019369]
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(3), 561-572.
[] [PMID: 1346755]
Zeng, L.; Zhou, M.M. Bromodomain: an acetyl-lysine binding domain. FEBS Lett., 2002, 513(1), 124-128.
[] [PMID: 11911891]
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(1), 33-43.
[] [PMID: 14731392]
Filippakopoulos, P.; Picaud, S.; Mangos, M.; Keates, T.; Lambert, J.P.; Barsyte-Lovejoy, D.; Felletar, I.; Volkmer, R.; Müller, S.; Pawson, T.; Gingras, A.C.; Arrowsmith, C.H.; Knapp, S. Histone recognition and large-scale structural analysis of the human bromodomain family. Cell, 2012, 149(1), 214-231.
[] [PMID: 22464331]
Muller, S.; Filippakopoulos, P.; Knapp, S. Bromodomains as therapeutic targets. Expert Rev. Mol. Med., 2011, 13e29
[] [PMID: 21933453]
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(6735), 491-496.
[] [PMID: 10365964]
Mujtaba, S.; Zeng, L.; Zhou, M.M. Structure and acetyl-lysine recognition of the bromodomain. Oncogene, 2007, 26(37), 5521-5527.
[] [PMID: 17694091]
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(7370), 529-533.
[] [PMID: 21964340]
Sanchez, R.; Meslamani, J.; Zhou, M.M. The bromodomain: from epigenome reader to druggable target. Biochim. Biophys. Acta, 2014, 1839(8), 676-685.
[] [PMID: 24686119]
Filippakopoulos, P.; Knapp, S. Targeting bromodomains: epigenetic readers of lysine acetylation. Nat. Rev. Drug Discov., 2014, 13(5), 337-356.
[] [PMID: 24751816]
Sanchez, R.; Zhou, M.M. The role of human bromodomains in chromatin biology and gene transcription. Curr. Opin. Drug Discov. Devel., 2009, 12(5), 659-665.
[PMID: 19736624]
Ott, C.J.; Kopp, N.; Bird, L.; Paranal, R.M.; Qi, J.; Bowman, T.; Rodig, S.J.; Kung, A.L.; Bradner, J.E.; Weinstock, D.M. BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood, 2012, 120(14), 2843-2852.
[] [PMID: 22904298]
Fujisawa, T.; Filippakopoulos, P. Functions of bromodomain-containing proteins and their roles in homeostasis and cancer. Nat. Rev. Mol. Cell Biol., 2017, 18(4), 246-262.
[] [PMID: 28053347]
Pervaiz, M.; Mishra, P.; Günther, S. Bromodomain drug discovery - the past, the present and the future. Chem. Rec., 2018, 18(12), 1808-1817.
[] [PMID: 30289209]
Smith, S.G.; Zhou, M.M. The bromodomain: a new target in emerging epigenetic medicine. ACS Chem. Biol., 2016, 11(3), 598-608.
[] [PMID: 26596782]
Galdeano, C.; Ciulli, A. Selectivity on-target of bromodomain chemical probes by structure-guided medicinal chemistry and chemical biology. Future Med. Chem., 2016, 8(13), 1655-1680.
[] [PMID: 27193077]
Ferri, E.; Petosa, C.; McKenna, C.E. Bromodomains: structure, function and pharmacology of inhibition. Biochem. Pharmacol., 2016, 106, 1-18.
[] [PMID: 26707800]
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(17), 7346-7359.
[] [PMID: 22788793]
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(1), 81-90.
[] [PMID: 16426974]
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(4), 531-541.
[] [PMID: 21513889]
Gerona-Navarro, G. Yoel-Rodríguez; 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(7), 2040-2043.
[] [PMID: 21271695]
Philpott, M.; Yang, J.; Tumber, T.; Fedorov, O.; Uttarkar, S.; Filippakopoulos, P.; Picaud, S.; Keates, T.; Felletar, I.; Ciulli, A.; Knapp, S.; Heightman, T.D. Bromodomain-peptide displacement assays for interactome mapping and inhibitor discovery. Mol. Biosyst., 2011, 7(10), 2899-2908.
[] [PMID: 21804994]
Hewings, D.S.; Wang, M.; Philpott, M.; Fedorov, O.; Uttarkar, S.; Filippakopoulos, P.; Picaud, S.; Vuppusetty, C.; Marsden, B.; Knapp, S.; Conway, S.J.; Heightman, T.D. 3,5-dimethylisoxazoles act as acetyl-lysine-mimetic bromodomain ligands. J. Med. Chem., 2011, 54(19), 6761-6770.
[] [PMID: 21851057]
Rooney, T.P.C.; 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.; Müller, 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-π interaction. Angew. Chem. Int. Ed. Engl., 2014, 53(24), 6126-6130.
[] [PMID: 24821300]
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.C.; Tumber, A.; Yapp, C.; Filippakopoulos, P.; Bunnage, M.E.; Müller, 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(26), 9308-9319.
[] [PMID: 24946055]
Hammitzsch, A.; Tallant, C.; Fedorov, O.; O’Mahony, A.; Brennan, P.E.; Hay, D.A.; Martinez, F.O.; Al-Mossawi, M.H.; de Wit, J.; Vecellio, M.; Wells, C.; Wordsworth, P.; Müller, S.; Knapp, S.; Bowness, P. CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses. Proc. Natl. Acad. Sci. USA, 2015, 112(34), 10768-10773.
[] [PMID: 26261308]
Xu, M.; Unzue, A.; Dong, J.; Spiliotopoulos, D.; Nevado, C.; Caflisch, A. Discovery of CREBBP bromodomain inhibitors by high-throughput docking and hit optimization guided by molecular dynamics. J. Med. Chem., 2016, 59(4), 1340-1349.
[] [PMID: 26125948]
Unzue, A.; Xu, M.; Dong, J.; Wiedmer, L.; Spiliotopoulos, D.; Caflisch, A.; Nevado, C. Fragment-based design of selective nanomolar ligands of the CREBBP bromodomain. J. Med. Chem., 2016, 59(4), 1350-1356.
[] [PMID: 26043365]
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.; Müller, 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(23), 5106-5119.
[] [PMID: 26552700]
Filippakopoulos, P.; Picaud, S.; Felletar, I.; Hay, D.; Fedorov, O.; Martin, S.; Chaikuad, A.; von Delft, F.; Brennan, P.; Arrowsmith, C.H.; Edwards, A.M.; Bountra, C.; Knapp, S. Structural Genomics Consortium (SGC). 4NR6: Crystal structure of the bromodomain of human CREBBP in complex with an oxazepin ligand, . 2018.
Popp, T.A.; Tallant, C.; Rogers, C.; Fedorov, O.; Brennan, P.E.; Müller, S.; Knapp, S.; Bracher, F. Development of selective CBP/P300 benzoxazepine bromodomain inhibitors. J. Med. Chem., 2016, 59(19), 8889-8912.
[] [PMID: 27673482]
Zucconi, B.E.; Luef, B.; Xu, W.; Henry, R.A.; Nodelman, I.M.; Bowman, G.D.; Andrews, A.J.; Cole, P.A. Modulation of p300/CBP acetylation of nucleosomes by bromodomain ligand I-CBP112. Biochemistry, 2016, 55(27), 3727-3734.
[] [PMID: 27332697]
Taylor, A.M.; Côté, A.; Hewitt, M.C.; Pastor, R.; Leblanc, Y.; Nasveschuk, C.G.; Romero, F.A.; Crawford, T.D.; Cantone, N.; Jayaram, H.; Setser, J.; Murray, J.; Beresini, M.H.; de Leon Boenig, G.; Chen, Z.; Conery, A.R.; Cummings, R.T.; Dakin, L.A.; Flynn, E.M.; Huang, O.W.; Kaufman, S.; Keller, P.J.; Kiefer, J.R.; Lai, T.; Li, Y.; Liao, J.; Liu, W.; Lu, H.; Pardo, E.; Tsui, V.; Wang, J.; Wang, Y.; Xu, Z.; Yan, F.; Yu, D.; Zawadzke, L.; Zhu, X.; Zhu, X.; Sims, R.J., III; Cochran, A.G.; Bellon, S.; Audia, J.E.; Magnuson, S.; Albrecht, B.K. Fragment-based discovery of a selective and cell-active benzodiazepinone CBP/EP300 bromodomain inhibitor (CPI-637). ACS Med. Chem. Lett., 2016, 7(5), 531-536.
[] [PMID: 27190605]
Crawford, T.D.; Romero, F.A.; Lai, K.W.; Tsui, V.; Taylor, A.M.; de Leon Boenig, G.; Noland, C.L.; Murray, J.; Ly, J.; Choo, E.F.; Hunsaker, T.L.; Chan, E.W.; Merchant, M.; Kharbanda, S.; Gascoigne, K.E.; Kaufman, S.; Beresini, M.H.; Liao, J.; Liu, W.; Chen, K.X.; Chen, Z.; Conery, A.R.; Côté, A.; Jayaram, H.; Jiang, Y.; Kiefer, J.R.; Kleinheinz, T.; Li, Y.; Maher, J.; Pardo, E.; Poy, F.; Spillane, K.L.; Wang, F.; Wang, J.; Wei, X.; Xu, Z.; Xu, Z.; Yen, I.; Zawadzke, L.; Zhu, X.; Bellon, S.; Cummings, R.; Cochran, A.G.; Albrecht, B.K.; Magnuson, S. Discovery of a potent and selective in vivo probe (GNE-272) for the bromodomains of CBP/EP300. J. Med. Chem., 2016, 59(23), 10549-10563.
[] [PMID: 27682507]
Romero, F.A.; Murray, J.; Lai, K.W.; Tsui, V.; Albrecht, B.K.; An, L.; Beresini, M.H.; de Leon Boenig, G.; Bronner, S.M.; Chan, E.W.; Chen, K.X.; Chen, Z.; Choo, E.F.; Clagg, K.; Clark, K.; Crawford, T.D.; Cyr, P.; de Almeida Nagata, D.; Gascoigne, K.E.; Grogan, J.L.; Hatzivassiliou, G.; Huang, W.; Hunsaker, T.L.; Kaufman, S.; Koenig, S.G.; Li, R.; Li, Y.; Liang, X.; Liao, J.; Liu, W.; Ly, J.; Maher, J.; Masui, C.; Merchant, M.; Ran, Y.; Taylor, A.M.; Wai, J.; Wang, F.; Wei, X.; Yu, D.; Zhu, B.Y.; Zhu, X.; Magnuson, S. GNE-781, a highly advanced potent and selective bromodomain inhibitor of cyclic adenosine monophosphate response element binding protein, binding protein (CBP). J. Med. Chem., 2017, 60(22), 9162-9183.
[] [PMID: 28892380]
Lai, K.W.; Romero, F.A.; Tsui, V.; Beresini, M.H.; de Leon Boenig, G.; Bronner, S.M.; Chen, K.; Chen, Z.; Choo, E.F.; Crawford, T.D.; Cyr, P.; Kaufman, S.; Li, Y.; Liao, J.; Liu, W.; Ly, J.; Murray, J.; Shen, W.; Wai, J.; Wang, F.; Zhu, C.; Zhu, X.; Magnuson, S. Design and synthesis of a biaryl series as inhibitors for the bromodomains of CBP/P300. Bioorg. Med. Chem. Lett., 2018, 28(1), 15-23.
[] [PMID: 29169673]
Bronner, S.M.; Murray, J.; Romero, F.A.; Lai, K.W.; Tsui, V.; Cyr, P.; Beresini, M.H.; de Leon Boenig, G.; Chen, Z.; Choo, E.F.; Clark, K.R.; Crawford, T.D.; Jayaram, H.; Kaufman, S.; Li, R.; Li, Y.; Liao, J.; Liang, X.; Liu, W.; Ly, J.; Maher, J.; Wai, J.; Wang, F.; Zheng, A.; Zhu, X.; Magnuson, S. A unique approach to design potent and selective cyclic adenosine monophosphate response element binding protein, binding protein (CBP) inhibitors. J. Med. Chem., 2017, 60(24), 10151-10171.
[] [PMID: 29155580]
Spiliotopoulos, D.; Zhu, J.; Wamhoff, E.C.; Deerain, N.; Marchand, J.R.; Aretz, J.; Rademacher, C.; Caflisch, A. Virtual screen to NMR (VS2NMR): discovery of fragment hits for the CBP bromodomain. Bioorg. Med. Chem. Lett., 2017, 27(11), 2472-2478.
[] [PMID: 28410781]
Hügle, M.; Lucas, X.; Ostrovskyi, D.; Regenass, P.; Gerhardt, S.; Einsle, O.; Hau, M.; Jung, M.; Breit, B.; Günther, S.; Wohlwend, D. Beyond the BET family: targeting CBP/p300 with 4-Acyl Pyrroles. Angew. Chem. Int. Ed. Engl., 2017, 56(41), 12476-12480.
[] [PMID: 28766825]
Xiang, Q.; Wang, C.; Zhang, Y.; Xue, X.; Song, M.; Zhang, C.; Li, C.; Wu, C.; Li, K.; Hui, X.; Zhou, Y.; Smaill, J.B.; Patterson, A.V.; Wu, D.; Ding, K.; Xu, Y. Discovery and optimization of 1-(1H-indol-1-yl)ethanone derivatives as CBP/EP300 bromodomain inhibitors for the treatment of castration-resistant prostate cancer. Eur. J. Med. Chem., 2018, 147, 238-252.
[] [PMID: 29448139]
CellCentric. CCSI477 in patients, 2020. Available at:.

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