A structure-based approach to discover a potential isomerase Pin1 inhibitor for cancer therapy using computational simulation and biological studies.

Peptidyl-prolyl cis/trans isomerase Pin1 occupies a prominent role in preventing the development of certain malignant tumors. Pin1 is considered a target for the treatment of related malignant tumors, so the identification of novel Pin1 inhibitors is particularly urgent. In this study, we preliminarily predicted eight candidates from FDA-approved drug database as the potential Pin1 inhibitors through virtual screening combined with empirical screening. Therefore, we selected these eight candidates and tested their binding affinity and inhibitory activity against Pin1 using fluorescence titration and PPIase activity assays, respectively. Subsequently, we found that four FDA-approved drugs showed good binding affinities and inhibition effects. In addition, we also observed that bexarotene can reduce cell viability in a dose-dependent and time-dependent manner and induce apoptosis. Finally, we inferred that residues K63, R68 and R69 are important in the binding process between bexarotene and Pin1. All in all, repurposing of FDA-approved drugs to inhibit Pin1 may provide a promising insight into the identification and development of new treatments for certain malignant tumors. [Display omitted] • Fluorescence titration assays demonstrated bexarotene possess a good binding ability for Pin1. • Enzymatic activity assays showed bexarotene possess a good inhibition rate for Pin1. • Cell assays unveiled that bexarotene reduces cancer cell viability and induces apoptosis. • Computational simulation and biological assays revealed that bexarotene interacts with residues K63, R68 and R69 of Pin1. [ABSTRACT FROM AUTHOR]