Biological Function of Pin1 in Vivo and Its Inhibitors for Preclinical Study: Early Development, Current Strategies, and Future Directions

Abstract

Peptidyl-prolyl cis/trans isomerase family (PPIase) is structurally divided into three subfamilies, cyclophilins (Cyps), FK506-binding proteins (FKBPs), and parvulins. Pin1 belongs to the parvulin family and is the only enzyme capable of isomerizing the phosphorylated Ser/Thr-Pro motif (p-Ser/Thr-Pro) in its interacting proteins. Due to its multibiological functions in vivo, including folding, intracellular signaling, transcription, cell cycle progression, and apoptosis, Pin1 is extensively studied as a promising drug target for various human diseases, especially cancer. In this Perspective, we summarized the literature covering diverse classes of Pin1 inhibitors and the inhibition mechanism, aiming to provide insights for the design of potent Pin1 inhibitors and suggest alternative strategies for developing potent Pin1 inhibitors.

Discovery of 5-Hydroxy-1,4-naphthoquinone (Juglone) Derivatives as Dual Effective Agents Targeting Platelet-Cancer Interplay through Protein Disulfide Isomerase Inhibition

“…Besides PDIs, the peptidyl-prolyl isomerase, Pin1, is known as a potential target of juglone that can be covalently thiol modified by juglone. 64,65 In the present study, we did not investigate if Pin1 is susceptible to the juglone derivatives that have Michael acceptor(s). However, it seems to be unlikely that Pin1 inhibition plays a major role in their bioactivities reported here.…”