2021 Fiscal Year Final Research Report
Exploration of drugs to potently and selectively inhibit human CYP2J2 activity and evaluation of their antitumor effect on human tumor cell lines
| Project/Area Number |
19K07063
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
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| Research Institution | Tokyo University of Pharmacy and Life Science (2021)
Shinshu University (2019-2020) |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 降圧薬 / CYP2J2 / 分子標的薬 / 抗腫瘍効果 |
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| Outline of Final Research Achievements |
Inhibitory effects of antihypertensive drugs on catalytic activities of major drug-metabolizing CYP enzymes (CYP1A2, CYP2C9, CYP2D6, and CYP3A4) were examined with human liver microsomes to clarify the inhibition selectivity for CYP2J2. Furthermore, antitumor effects of antihypertensive drugs were investigated with human tumor cell lines. Among the antihypertensive drugs tested, it was suggested that azelnidipine shows a highly selective inhibition against CYP2J2. A lot of antihypertensive drugs exhibited antiproliferative effects on human tumor cell lines (GIST-T1 and SK-HEP-1), although no drugs to potentiate antiproliferative effects of sorafenib and sunitinib were found under the current conditions. Further studies are needed to evaluate antitumor effects of antihypertensive drugs with cell lines highly expressing CYP2J2.
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| Free Research Field |
薬物代謝学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、申請者らが見出したCYP2J2活性を強力に阻害する降圧薬のうち、アゼルニジピンがCYP2J2活性を選択的に阻害し、さらにヒト腫瘍株化細胞の増殖を強く抑制する可能性が示唆された。本研究成果を基盤にして、今後、より詳細な解析が進めば、抗がん薬の副作用（高血圧）の軽減だけでなく、抗腫瘍効果の増強にも大きく寄与する薬剤の創出が期待される。
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