2016
DOI: 10.1080/07391102.2016.1217276
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Molecular docking and dynamics simulation study of flavonoids as BET bromodomain inhibitors

Abstract: Bromodomains (BRDs) are the epigenetic proteins responsible for transcriptional regulation through its interaction with methylated or acetylated histone residues. The lysine residues of Bromodomain-1 (BD1) of Brd4 undergo ε-N-Acetylation posttranslational modifications to control transcription of genes. Due to its role in diverse cellular functions, Brd4 of bromodomain family, was considered as a prominent target for many diseases such as cancer, obesity, kidney disease, lung fibrosis, inflammatory diseases, e… Show more

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Cited by 44 publications
(17 citation statements)
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“…There are currently 61 known distinct human bromodomains that are contained in 46 different proteins [27]. Bromodomains have been of intense therapeutic interest in recent years [28][29][30][31][32][33][34][35][36][37][38][39], as bromodomain inhibitors have been proposed as treatments for cancer, diabetes and inflammation. Much attention has been given to the bromodomain and extraterminal (BET) family, including Brd4 for which the first inhibitor was discovered in 2010 [40].…”
Section: Introductionmentioning
confidence: 99%
“…There are currently 61 known distinct human bromodomains that are contained in 46 different proteins [27]. Bromodomains have been of intense therapeutic interest in recent years [28][29][30][31][32][33][34][35][36][37][38][39], as bromodomain inhibitors have been proposed as treatments for cancer, diabetes and inflammation. Much attention has been given to the bromodomain and extraterminal (BET) family, including Brd4 for which the first inhibitor was discovered in 2010 [40].…”
Section: Introductionmentioning
confidence: 99%
“…Fisetin on the other hand, shows more contacts with residues Met105 and Met132. Previous reports of docking indicate that flavonoids have a notable preference towards these residues [26], in the case of fisetin, affinity for Cys136 has also been observed [46]. This hints to flavonoids having a significant affinity towards different residues beyond the Ac-pocket, while their aromatic character gives them selectivity for the WPF shelf.…”
mentioning
confidence: 76%
“…Bromodomain inhibitors may be classified on two broad categories: Kac mimicking and non-mimicking, the former being the most prominent [55]. Flavonoids belong to this category as their carbonyl groups are their main anchor towards Asn140 and Tyr97 [46]. Nonetheless, as shown on Figure 4, these interactions are not as populated as it might be expected.…”
Section: Molecular Dockingmentioning
confidence: 97%
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“…Out of these 177 protein sequences, 43 had DO term while 13 (out of these 43 sequences) were having homology with human proteome. Remaining 30 hypothetical uncharacterized protein sequences were observed which had DO term but were not homologous with human proteome 26,27 . Thus, the 30 uncharacterized proteins may be used as putative drug target for M. leprae.…”
Section: Methodsmentioning
confidence: 99%