Discovery of an EP300 Inhibitor using Structure-based Virtual Screening and Bioactivity Evaluation.

ABSTRACT:

Background

EP300 (E1A binding protein p300) played a significant role in serial diseases such as cancer, neurodegenerative disease. Therefore, it became a significant target.

Methods

Targeting EP300 discovery of a novel drug to alleviate these diseases. In this paper, 17 candidate compounds were obtained using a structure-based virtual screening approach, 4449-0460, with an IC₅₀ of 5.89 ± 2.08 uM, which was identified by the EP300 bioactivity test. 4449-0460 consisted of three rings. The middle benzene ring connected the 5-ethylideneimidazolidine-2,4-dione group and the 3-F-Phenylmethoxy group.

Results

Furthermore, the interaction mechanism between 4449-0460 and EP300 was explored by combining molecular dynamics (MD) simulations and binding free energy calc

SUBMITTER: Pan D 

PROVIDER: S-EPMC11348464 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature