| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
Inhibitors of α,β-tubulin polymerization or depolymerization are cytotoxic against tumor cells. On the other hand, γ-tubulin is forms the γ-tubulin ring complex (γ-TuRC), which is the starting point of α,β-tubulin polymerization in cells. In light of this phenomenon, γ-tubulin is an attractive target protein for the development of novel types of anticancer drugs. Previously, we have developed gatastatin, which does not affect α,β-tubulin polymerization and specifically inhibits γ-tubulin functions including GTP binding.
In this research, we attempted to structure-activity relationship study of gatastatin. As a result, O6-propargyl gatastatin, named "gatastatin G2", showed potent cytotoxicity. And also, this derivative both inhibits γ-tubulin-dependent nucleation and induces abnormal spindle formation, suggesting that gatastatin G2 is a more potent γ-tubulin-specific inhibitor than gatastatin and is a useful tool for investigating γ-tubulin function in cells.
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