2. Academic Validation
  3. Discovery of BAZ1A bromodomain inhibitors with the aid of virtual screening and activity evaluation

Discovery of BAZ1A bromodomain inhibitors with the aid of virtual screening and activity evaluation

  • Bioorg Med Chem Lett. 2021 Feb 1;33:127745. doi: 10.1016/j.bmcl.2020.127745.
Zhenyu Yang 1,  Yangli Zhou 2,  Lei Zhong 3
Affiliations

Affiliations

  • 1 Personalized Drug Therapy Key Laboratory of Sichuan Province, Department of Pharmacy, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China; School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0250, USA.
  • 2 State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
  • 3 Personalized Drug Therapy Key Laboratory of Sichuan Province, Department of Pharmacy, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China. Electronic address: [email protected].
PMID: 33333161 DOI: 10.1016/j.bmcl.2020.127745
Abstract

BAZ1A is a bromodomain-containing protein, and has been recognized as a potential target for multiple diseases, particularly Cancer. However, there is no BAZ1A inhibitor reported so far. In this study, we used a consensus docking/scoring strategy to screen for BAZ1A bromodomain inhibitors from commercial chemical libraries and an in-house chemical database. The retrieved hit compounds were evaluated experimentally and four compounds were found to be active against BAZ1A bromodomain. To the most active compounds, similarity and substructure searches were used to find more BAZ1A bromodomain inhibitors. Among all the obtained active compounds, Cpd-2 is the most potent one, which showed a KD value of 0.52 μM. The interaction model of Cpd-2 with BAZ1A bromodomain was revealed by molecular docking. In a cellular assay, Cpd-2 displayed good anti-viability activity against Cancer cell lines expressing a high level of BAZ1A. Overall, we discovered a number of BAZ1A bromodomain inhibitors for the first time, which can be a good starting point for subsequent drug discovery targeting BAZ1A bromodomain.

Keywords

BAZ1A; Bromodomain; Small molecule inhibitor; Virtual screening.

Figures
Products