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

Abstract

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.

Keywords:

• PIN1 inhibitors
• virtual screening
• molecular modelling
• pharmacophore
• drug design
• cancer

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors are grateful to the Associazione Italiana per la Ricerca sul Cancro — AIRC IG grant [No. 23566 to F. R.], POR FESR FVG 2014-2020: attività 1.3.b, CATHENA [V.C.] and Ministero della Salute — Ricerca Corrente.