Dataset Information
Discovery of an EP300 Inhibitor using Structure-based Virtual Screening and Bioactivity Evaluation.
Ontology highlight
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 calculation methods.Conclusion
The binding free energy of EP300 with 4449-0460 was -10.93 kcal/mol, and mainly came from the nonpolar energy term (ΔGnonpolar). Pro1074, Phe1075, Val1079, Leu1084, and Val1138 were the key residues in EP300/4449-0460 binding with more -1 kcal/mol energy contribution. 4449-0460 was a promising inhibitor targeting EP300, which had implications for the development of drugs for EP300-related diseases.
SUBMITTER: Pan D
PROVIDER: S-EPMC11348464 | biostudies-literature | 2024 Jun
REPOSITORIES: biostudies-literature
Publications
Discovery of an EP300 Inhibitor using Structure-based Virtual Screening and Bioactivity Evaluation.
Current pharmaceutical design 20240101 25
<h4>Background</h4>EP300 (E1A binding protein p300) played a significant role in serial diseases such as cancer, neurodegenerative disease. Therefore, it became a significant target.<h4>Methods</h4>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 IC<sub>50</sub> of 5.89 ± 2.08 uM, which was identified by the EP300 bioactivity test. 4449-0460 consisted o ...[more]