Studies on novel insulin-sensitizing agent based on SHIP2 inhibitors

Research Project

Project/Area Number	15K08020
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Drug development chemistry
Research Institution	University of Toyama
Principal Investigator	Toyooka Naoki 富山大学, 大学院理工学研究部(工学), 教授 (10217565)
Research Collaborator	SASAOKA Toshiyasu WADA Tutomu GODA Hiroaki
Project Period (FY)	2015-04-01 – 2018-03-31
Project Status	Completed (Fiscal Year 2017)
Budget Amount *help	¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000) Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords	インスリン抵抗性改善薬 / SHIP2 / Akt / ファーマコフォア / SHIP2阻害 / インシリコスクリーニング / 3T3-L1 / CP-2 / CP-3 / Aktのリン酸化 / Echelon社 / 3T3-L1脂肪細胞 / メタ置換ベンゼン / トリアゾール
Outline of Final Research Achievements	Among the oral diabetic drugs, insulin-sensitizing agent is insufficient. So the development of new insulin-sensitizing agent based upon novel mechanism is urgent matter. We have investigated on the development of inhibitor of SHIP2, which shows important role for insulin resistance in the insulin signal pathway. Based on the structure of our original new insulin-sensitizing agent, we designed new pharmacophore, and acquired candidate compounds using in silico screening. Furthermore we performed the synthetic development based on the structure of candidates. The evaluations of synthetic compounds using the phosphorylation of Akt resulted in the discovery of novel SHIP2 inhibitors.