ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Pharmacophore-based virtual screening, molecular docking, and molecular dynamics simulation for the identification of novel BRD4 (BD1) inhibitors

Junmin Dong and Xiaohua Hao

Phase Ⅰ clinical trial center, Beijing Shijitan Hospital, Capital Medical University, Beijing, China

E-mail: hxh3949@bjsjth.cn

Received: 11 September 2025  Accepted: 26 January 2026

Abstract:

Bromodomain-containing protein 4 (BRD4) BD1 protein, as an epigenetic target, plays an important role in the development and progression of cancer. In this study, a structure-based pharmacophore model for BRD4 (BD1) was constructed to screen 201,233 compounds from the SPECS database. Drug-likeness screening, molecular docking, molecular dynamics simulations, and ADMET predictions were followed to identify potential BRD4 (BD1) inhibitors. Results showed that the constructed pharmacophore 6P05_06 exhibited high sensitivity and specificity. Hierarchical virtual screening yielded 24 hit compounds. Among which, compound28818 showed the highest docking score and was predicted to possess favorable ADMET properties. Its binding free energy was found to be superior to that of the co-crystal ligand YF2. In silico analysis also indicated stronger and more extensive interactions of compound28818 with BRD4 (BD1), supporting its binding selectivity. These computational results suggested that compound28818 might serve as a potential BRD4 (BD1) inhibitor, and its predicted binding profile could offer valuable theoretical insights for the future design of novel selective BRD4 (BD1) inhibitors.

Keywords: Bromodomain-containing protein 4; Virtual screening; Pharmacophore molecular docking; Molecular dynamic simulation

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-026-04704-w

Chemical Papers 80 (5) 5253–5263 (2026)