New PIN1 inhibitors identified through a pharmacophore-driven, hierarchical consensus docking strategy

Journal of Enzyme Inhibition and Medicinal Chemistry

Marco Macchia¹  Giulio Poli¹  Miriana Di Stefano¹  Filippo Minutolo¹  Tiziano Tuccinardi¹  Joan Arias Estevez¹  Carlotta Granchi¹  Flavio Rizzolio²  Salvatore Parisi²  Isabella Caligiuri²  Vincenzo Canzonieri²  Matteo Mauceri²  Antonio Giordano³ 

[1] Department of Pharmacy, University of Pisa;Pathology Unit, CRO Aviano, National Cancer Institute, IRCCS;Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University;

关键词: pin1 inhibitors;    virtual screening;    molecular modelling;    pharmacophore;    drug design;    cancer;   

DOI  :  10.1080/14756366.2021.1979970

来源: DOAJ

【 摘 要 】

PIN1 is considered as a therapeutic target for a wide variety of tumours. However, most of known inhibitors are devoid of cellular activity despite their good enzyme inhibitory profile. Hence, the lack of effective compounds for the clinic makes the identification of novel PIN1 inhibitors a hot topic in the medicinal chemistry field. In this work, we reported a virtual screening study for the identification of new promising PIN1 inhibitors. A receptor-based procedure was applied to screen different chemical databases of commercial compounds. Based on the whole workflow, two compounds were selected and biologically evaluated. Both ligands, compounds VS1 and VS2, showed a good enzyme inhibitory activity and VS2 also demonstrated a promising antitumoral activity in ovarian cancer cells. These results confirmed the reliability of our in silico protocol and provided a structurally novel ligand as a valuable starting point for the development of new PIN1 inhibitors.

【 授权许可】

Unknown