Target identification of cortistatin A and development of anti-cancer drug lead

2015 Fiscal Year Final Research Report

• Project/Area Number: 25750384
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biomolecular chemistry
• Research Institution: Osaka University
• Principal Investigator: Kotoku Naoyuki 大阪大学, 薬学研究科(研究院), 助教 (20362618)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 活性発現の分子機構 / 海洋天然物 / 抗がんリード化合物

Outline of Final Research Achievements

Target identification study of cortistatin A, a highly potent and selective anti-angiogenic substance from marine sponge, was executed. Using an affinity probe molecule derived from a structurally simplified analogue compound that was developed by our group, chemical pulldown from cell lysate of endothelial cells was examined. After several attempts, we purified and identified some candidates of the target molecule using a photoaffinity probe molecule affinity probe molecules and LC-MS/MS analyses.
We also developed a second-generation synthetic method of the analogue compound, which allowed us to prepare various analogues with ease. Optimization study resulted in generating a promising lead compound, which showed potent and selective growth inhibitory activity against endothelial cells comparable to the natural cortistatin A. Moreover, it also exhibited significant in vivo anti-cancer effect upon oral administration.

Free Research Field

天然物有機化学