| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Outline of Final Research Achievements |
Metabolic activation of drugs to chemically reactive metabolites that are capable of modifying cellular macromolecules results in acute and/or idiosyncratic toxicities. Some marketed drugs are known to generate reactive metabolites and exhibit hepatotoxicity as side effects. These drugs must be carefully used on medication or withdrawn from the market in the worst-case. The current research is aiming to develop improved medicines to reduce the formation of reactive metabolites on the basis of the activation mechanism of three hapatotoxic drugs (benzbromarone, diclofenac, nevirapine).
First of all, we succeeded in the development of a novel fluorescent trapping agent to quantitatively and effectively detect reactive metabolites. Next, we designed and chemically synthesized multiple derivatives of the three drugs to avoid their metabolic activation. It was found that some of the derivatives are not subject to metabolic activation with remaining pharmacological activities as expected.
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