Structure-Guided Design and Development of Potent and Selective Dual Bromodomain 4 (BRD4)/Polo-like Kinase 1 (PLK1) Inhibitors
Year: 2018
Type: article
Abstract: The 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 IC 50 = 28 nM, PLK1 IC 50 = 40 nM). Compound 6 was found to be the most selective PLK1 inhibitor over BRD4 in our series (BRD4-BD1 IC 50 = 2579 nM, PLK1 IC 50 = 9.9 nM). Molecular docking studies with 23 and BRD4-BD1/PLK1 as well as with 6 corroborate the biochemical assay results.
Source: Journal of Medicinal Chemistry
Authors: Shuai Liu, Hailemichael O. Yosief, Lingling Dai, He Huang, Gagan Dhawan, Xiaofeng Zhang, Alex M. Muthengi, Justin Roberts, Dennis L. Buckley, Jennifer A. Perry, Lei Wu, James E. Bradner, Jun Qi, Wei Zhang
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Contraceptive Discovery, Development and Behavioral Research Center, Contraceptive Discovery, Development and Behavioral Research Center, Development of Novel Therapeutic Strategies in Human Leukemias, 2/2 The University of Massachusetts, Boston - Dana-Farber/Harvard Cancer Center U54 Comprehensive Partnership for Cancer Disparities Research
OpenAlex ID: W2888672154