Antidiabetic and Antiobesity Effects of Ampkinone (6f), a Novel Small Molecule Activator of AMP-Activated Protein Kinase

作者：Oh Sangmi; Kim Sung Jin; Hwang Jung Hwan; Lee Hyang Yeon; Ryu Min Jeong; Park Jongmin; Kim Soung Jung; Jo Young Suk; Kim Yong Kyung; Lee Chul Ho; Kweon Ki Ryang; Shong Minho^*; Park Seung Bum

来源：Journal of Medicinal Chemistry, 2010, 53(20): 7405-7413.

DOI：10.1021/jm100565d

Adenosine 5'-monophosphate (AMP) activated protein kinase (AMPK) has emerged as an attractive target molecule for the treatment of metabolic disorders, including obesity and type 2 diabetes. In this study, we identified a novel small molecule, ampkinone (6f), as an indirect AMPK activator, which was derived from the small molecule library constructed by diversity-oriented synthesis. Ampkinone stimulated the phosphorylation of AMPK via the indirect activation of AMPK in various cell lines. Ampkinone-mediated activation of AMPK required the activity of LKB1 and resulted in increased glucose uptake in muscle cells. In addition, ampkinone-treated DIO mice significantly reduced total body weight and overall fat mass. Histological examination and measurement of lipid parameters showed that ampkinone effectively improved metabolic abnormalities in the DIO mice model. Our results demonstrate that ampkinone, a small molecule with a privileged benzopyran substructure, has a potential as a new class of therapeutic agent for antidiabetic and antiobesity treatment via the indirect stimulation of AMPK.

• 出版日期2010-10-28