Submit Manuscript  

Article Details


Development of Pin1 Inhibitors and their Potential as Therapeutic Agents

Author(s):

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 and Tomoichiro Asano*   Pages 1 - 14 ( 14 )

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

Affiliation:

From the Department of Medical Science, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551, From the Department of Medical Science, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551, From the Department of Medical Science, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551, From the Department of Medical Science, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551, From the Department of Medical Science, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551, From the Department of Medical Science, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551, From the Department of Medical Science, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551, The Division of Diabetes and Metabolism, Institute for Adult Diseases, Asahi Life Foundation, Chuo-ku, Tokyo 103-0002, Department of Clinical Cell Biology, Chiba University Graduate School of Medicine, Chiba City, Chiba, 260-8670, The Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Drug Discovery Initiative, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, From the Department of Medical Science, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551



Read Full-Text article