Development of Pin1 inhibitors and their potential as therapeutic agents

The prolyl isomerase Pin1 is a unique enzyme, which isomerizes the cis-trans con-formation between pSer/pThr and proline and thereby regulates the function, stability and/or subcellular distribution of its target proteins. Such regulations by Pin1 are involved in numer-ous physiological functions as well as the pathogenic mechanisms underlying various dis-eases. Notably, Pin1 deficiency or inactivation is a potential cause of Alzheimer’s disease, since Pin1 induces the degradation of Tau. In contrast, Pin1 overexpression is highly corre-lated with the degree of malignancy of cancers, as Pin1 controls a number of oncogenes and tumor suppressors. Accordingly, Pin1 inhibitors as anti-cancer drugs have been developed. Interestingly, recent intensive studies have demonstrated Pin1 to be responsible for the onset or development of nonalcoholic steatosis, obesity, atherosclerosis, lung fibrosis, heart failure and so on, all of which have been experimentally induced in Pin1 deficient mice. In this review, we discuss the possible applications of Pin1 inhibitors to a variety of diseases including malignant tumors and also introduce the recent advances in Pin1 inhibitor research, which have been reported.