Development of PIN1 inhibitors

PIN1 is a peptidyl-prolyl isomerase that binds phospho-Ser/Thr-Pro motifs in proteins and catalyzes the cis–trans isomerization of proline peptide bonds. PIN1 is overexpressed in several cancers including high-grade serous ovarian cancer. However, but 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.

Part of our team is dedicated to develop new potent PIN1 inhibitors.



New PIN1 inhibitors identified through a pharmacophore-driven, hierarchical consensus docking strategy. Poli G, Di Stefano M, Estevez JA, Minutolo F, Granchi C, Giordano A, Parisi S, Mauceri M, Canzonieri V, Macchia M, Caligiuri I, Tuccinardi T, Rizzolio F. J Enzyme Inhib Med Chem. 2022, 37(1):145-150.


Peptidyl-prolyl isomerases in human pathologies. Tuccinardi T, Rizzolio F. Front Pharmacol. 2019, 10:794.


Virtual screening identifies a PIN1 inhibitor with possible antiovarian cancer effects. Russo Spena C, De Stefano L, Poli G, Granchi C, El Boustani M, Ecca F, Grassi G, Grassi M, Canzonieri V, Giordano A, Tuccinardi T, Caligiuri I, Rizzolio F. J Cell Physiol. 2019, 234(9):15708-15716.


A Guide to PIN1 Function and Mutations Across Cancers. El Boustani M, De Stefano L, Caligiuri I, Mouawad N, Granchi C, Canzonieri V, Tuccinardi T, Giordano A, Rizzolio F. Front Pharmacol. 2019, 9:1477.


Liposomal delivery of a Pin1 inhibitor complexed with cyclodextrins as new therapy for high-grade serous ovarian cancer. Spena CR, De Stefano L, Palazzolo S, Salis B, Granchi C, Minutolo F, Tuccinardi T, Fratamico R, Crotti S, D’Aronco S, Agostini M, Corona G, Caligiuri I, Canzonieri V, Rizzolio F. J Control Release. 2018, 281:1-10.

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