Abstract
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.
[66]
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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.
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[
http://dx.doi.org/10.1021/acs.jmedchem.6b01022] [PMID:
27682507]
[68]
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).
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[
http://dx.doi.org/10.1021/acs.jmedchem.7b00796] [PMID:
28892380]
,
Mingming Zhang*
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