2022 Fiscal Year Final Research Report
Development of selective nuclear receptor downregulator
| Project/Area Number |
19K07009
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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 47010:Pharmaceutical chemistry and drug development sciences-related
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| Research Institution | National Institute of Health Sciences |
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Principal Investigator |
Shoda Takuji 国立医薬品食品衛生研究所, 有機化学部, 室長 (60435708)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | アンタゴニスト / TNBC |
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| Outline of Final Research Achievements |
Recently, it was suggested that ERβ may be involved in the growth of triple-negative breast cancer (TNBC), and therefore, ERβ-selective antagonists were considered to be molecular targets for TNBC. We designed and synthesized WC10, a long-chain alkyl group attached to WAY-202196, a ligand for ERβ, in seven steps. WC10 showed high selectivity for ERβ as well as WAY-202196. WC10 also showed ERβ-selective antagonist activity in the forced expression system. Furthermore, WC10 showed an inhibitory effect on cell proliferation of MDA-MB-231 cells. These results suggest that WC10 is an ERβ-selective antagonist and may be a potential molecular targeted drug for TNBC.
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| Free Research Field |
創薬化学
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| Academic Significance and Societal Importance of the Research Achievements |
トリプルネガティブ乳がん（TNBC）は予後不良で知られる乳がんであり，治療に有効な分子標的の探索が精力的に行われています．近年，ERβが分子標的になりうることが報告されたことから，我々の知見を基に，新規のERβアンタゴニストの開発を行いました．本研究でデザイン合成したWC10はTNBCの細胞に対し細胞増殖抑制効果を示したことから，TNBCの治療薬になる可能性が得られました．
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