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

Peptidyl-prolyl cis/trans isomerase family (PPIase) isstructurallydivided into three subfamilies, cyclophilins (Cyps), FK506-bindingproteins (FKBPs), and parvulins. Pin1 belongs to the parvulin familyand is the only enzyme capable of isomerizing the phosphorylated Ser/Thr-Promotif (p-Ser/Thr-Pro) in its interacting proteins. Due to its multibiologicalfunctions in vivo, including folding, intracellular signaling, transcription,cell cycle progression, and apoptosis, Pin1 is extensively studiedas a promising drug target for various human diseases, especiallycancer. In this Perspective, we summarized the literature coveringdiverse classes of Pin1 inhibitors and the inhibition mechanism, aimingto provide insights for the design of potent Pin1 inhibitors and suggestalternative strategies for developing potent Pin1 inhibitors.