Discovery of potent heat shock protein 90 (Hsp90) inhibitors: structure-based virtual screening, molecular dynamics simulation, and biological evaluation.

ABSTRACT: Heat shock protein 90 (Hsp90) is considered an attractive therapeutic target for cancer treatment due to its high expression in many cancers. In this study, four potent Hsp90 inhibitors (HPs 1-4) were identified using structure-based virtual screening. Among them, HP-4 exhibited the most potent inhibitory effects (IC₅₀ = 17.64 ± 1.45 nM) against the Hsp90 protein, which was about 7.7 times stronger than that of MPC-3100 (a positive inhibitor targeting Hsp90). In vitro cytotoxicity assay suggested that HP-4 could effectively inhibit the proliferation of a series of tumour cells, including HCT-116, HeLa, A549, A2780, DU145, HepG2 and A498. Furthermore, in vivo assay displayed that HP-4 had significant anti-tumour effects on HCT-116 cell-derived xenograft models. These data demonstrate that HP-4 could be a potential lead compound for the further investigation of anti-tumour drugs.

SUBMITTER: Xu Y 

PROVIDER: S-EPMC10294771 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature