Development of Pin1 Inhibitors and their Potential as Therapeutic Agents

Yusuke       Nakatsu; Yasuka       Matsunaga; Koji       Ueda; Takeshi       Yamamotoya; Yuki       Inoue; Masa-ki       Inoue; Yu       Mizuno; Akifumi       Kushiyama; Hiraku       Ono; Midori       Fujishiro; Hisanaka       Ito; Takayoshi       Okabe; Tomoichiro       Asano
doi:10.2174/0929867325666181105120911
Abstract

The prolyl isomerase Pin1 is a unique enzyme, which isomerizes the cis-trans conformation 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 numerous physiological functions as well as the pathogenic mechanisms underlying various diseases. 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 correlated 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.
Keywords: Prolyl isomerase Pin1, Pin1 inhibitors, juglone, ATRA, cancer, metabolic syndromes, fibrosis
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DOI https://dx.doi.org/10.2174/0929867325666181105120911	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
Current Medicinal Chemistry

Development of Pin1 Inhibitors and their Potential as Therapeutic Agents

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