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Structure-Guided Design and Development of Potent and Selective Dual Bromodomain 4 (BRD4)/Polo-like Kinase 1 (PLK1) Inhibitors

dc.contributor.authorLiu, Shuai
dc.contributor.authorYosief, Hailemichael O.†
dc.contributor.authorDai, Lingling
dc.contributor.authorHuang, He
dc.contributor.authorDhawan, Gagan
dc.contributor.authorZhang, Xiaofeng
dc.contributor.authorMuthengi, Alex
dc.contributor.authorRoberts, Justin
dc.contributor.authorBuckley, Dennis L.
dc.contributor.authorPerry, Jennifer A.
dc.contributor.authorWu, Lei
dc.contributor.authorBradner, James E.
dc.contributor.authorQi, Jun
dc.contributor.authorZhang, Wei
dc.date.accessioned2021-11-09T07:14:24Z
dc.date.available2021-11-09T07:14:24Z
dc.date.issued2018
dc.identifier.citationJournal of Medicinal Chemistryen_US
dc.identifier.urihttp://repository.tharaka.ac.ke/xmlui/handle/1/3172
dc.description.abstractThe simultaneous inhibition of polo-like kinase 1 (PLK1) and BRD4 bromodomain by a single molecule could lead to the development of an effective therapeutic strategy for a variety of diseases in which PLK1 and BRD4 are implicated. Compound 23 has been found to be a potent dual kinase−bromodomain inhibitor (BRD4-BD1 IC50 = 28 nM, PLK1 IC50 = 40 nM). Compound 6 was found to be the most selective PLK1 inhibitor over BRD4 in our series (BRD4-BD1 IC50 = 2579 nM, PLK1 IC50 = 9.9 nM). Molecular docking studies with 23 and BRD4-BD1/PLK1 as well as with 6 corroborate the biochemical assay results.en_US
dc.language.isoen_USen_US
dc.titleStructure-Guided Design and Development of Potent and Selective Dual Bromodomain 4 (BRD4)/Polo-like Kinase 1 (PLK1) Inhibitorsen_US
dc.typeArticleen_US


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