| RRC ID |
87618
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| 著者 |
Yasunaga R, Nakano M, Kyuma T, Fujii K, Inui H, Akutsu J, Yonemura I, Inoue T, Suwa A, Yoshizane T, Nakao A, Mori Y.
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| タイトル |
A novel insecticide cybenzoxasulfyl potently binds to vesicular acetylcholine transporter and disrupts the storage and release of acetylcholine in insects.
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| ジャーナル |
Biochem Biophys Res Commun
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| Abstract |
Agrochemicals play an important role in solving global food problems and achieving a safe and sustainable society by protecting crops from pests and diseases, controlling weeds, and protecting human and animal health. The evolution of insecticide-resistant pests is a serious problem worldwide, and repeated use of insecticides with the same mode of action (MoA) promotes the evolution of resistance. Therefore, the development of insecticides with novel MoAs is important for controlling pests that are resistant to existing insecticides, thereby preventing the depletion of effective insecticides. In this study, based on genetic studies in Caenorhabditis elegans and biochemical studies in Drosophila melanogaster, we found that a new insecticide under development, cybenzoxasulfyl, binds directly to the vesicular acetylcholine transporter (VAChT) with low nanomolar Kd values and inhibits acetylcholine (ACh) storage in synaptic vesicles and cholinergic signaling, thereby exerting insecticidal effects. Competitive binding assays against [3H]-vesamicol suggested that cybenzoxasulfyl occupies the same binding site on VAChT in a different way than vesamicol, which has long been studied as a VAChT inhibitor. We have also revealed the metabolic pathway of cybenzoxasulfyl in Spodoptera litura, an agriculturally important lepidopteran pest, and the inhibitory effects retained by its immediately downstream metabolites using pharmacokinetic analysis and binding assay. Hence, cybenzoxasulfyl represents a promising new insecticide that acts on the VAChT and is expected to provide long-lasting activity against a variety of invertebrate pests that have evolved resistance.
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| 巻・号 |
763
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| ページ |
151792
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| 公開日 |
2025-5-12
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| DOI |
10.1016/j.bbrc.2025.151792
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| PII |
S0006-291X(25)00506-6
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| PMID |
40233436
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| MeSH |
Acetylcholine* / metabolism
Animals
Drosophila melanogaster / drug effects
Drosophila melanogaster / metabolism
Insecticides* / chemistry
Insecticides* / metabolism
Insecticides* / pharmacology
Spodoptera / drug effects
Spodoptera / metabolism
Synaptic Vesicles / drug effects
Synaptic Vesicles / metabolism
Vesicular Acetylcholine Transport Proteins* / antagonists & inhibitors
Vesicular Acetylcholine Transport Proteins* / metabolism
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| リソース情報 |
| ショウジョウバエ |
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