2023 Fiscal Year Final Research Report
Development of novel mu-opioid receptor-selective opioids with less adverse effects
| Project/Area Number |
21K06584
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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 47040:Pharmacology-related
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
宮野 加奈子 東京慈恵会医科大学, 医学部, 准教授 (50597888)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | バイアスドリガンド / 二量体化受容体 / GPCR / オピオイド受容体 / 新規オピオイド化合物 / βアレスチン / 副作用 / オピオイドクライシス |
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| Outline of Final Research Achievements |
The current trend in the development of novel opioid analgesics, which are less likely to cause tolerance or side effects is 1) selective agonists of opioid μ/δ dimerized receptors, and 2) biased compounds that activate only G protein pathways mainly involved in analgesia and do not affect β-arrestin pathways that cause side effects.
We have identified the compound SYK-X, that possesses both above characteristics, and have demonstrated in animal experiments that it exhibits analgesic effects equivalent to morphine and is also effective even in morphine-resistant animals. We aim to develop SYK-X as an attractive seed for further drug discovery.
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| Free Research Field |
分子神経薬理学、疼痛学、支持・緩和医療学
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| Academic Significance and Societal Importance of the Research Achievements |
がんの痛みの軽減等に広く用いられている医療用オピオイド鎮痛薬は副作用が必発であるため、副作用の少ない新規オピオイド製剤の開発が求められている。今回同定したμ/δ二量体化受容体アゴニストかつG蛋白バイアスドアゴニストSYK-Xは、動物実験においてもモルヒネに匹敵する鎮痛効果を有し、かつモルヒネ耐性は認められなかった。同化合物をシーズとして実装可能なオピオイド創薬が進められ得ると考える。
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