2021 Fiscal Year Final Research Report
Selective HIF activation by allosteric PHD inhibition: a novel therapeutic compound for chronic kidney disease
| Project/Area Number |
19K17746
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | Saga University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | HIF活性化 / PHD阻害 |
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| Outline of Final Research Achievements |
In this study, we have focused on the molecular target HIF (hypoxia-inducible factor), which can uniquely improve ischemic symptoms, and have been developing oral ischemic therapeutic agents. In this study, we have discovered a small molecule compound, PyrzA, which inhibits PHD, and have also developed a synthetic method. We have also attempted to improve pharmacokinetic parameters, synthesized derivatives, and synthesized about 30 new compounds. In a study of HIF activation in a luciferase assay using cells of compounds with improved pharmacokinetic parameters, we found a compound that showed similar activation at a concentration about 50-fold lower than that of PyrzA. The results were similar to those of PyrzA, but at concentrations about 50-fold lower than PyrzA.
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| Free Research Field |
創薬化学
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| Academic Significance and Societal Importance of the Research Achievements |
慢性腎疾患は初期症状を含めると約1,300万人が罹患している（日本腎臓学会）。疾患が進行すると虚血症状が現れる。本研究によって見いだした分子は経口虚血治療薬として、利用可能であり設計から、本研究による新規化合物は、2-OGの構造を持たず、副作用の少ない虚血治療薬となりうる。これは、患者の経済的負担とQOL（quality of life）の向上に大いに期待できる。
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