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Among the synthesized compounds, FM-2665 (A14) showed the highest overall activity against Plutella xylostella, Tetranychus cinnabarinu, and Myzus persicae, with LC50 values of 0.127, 0.604, and 0.496 mg\/L, respectively. On the basis of the LC50 values, FM-2665 was 6.68-fold more potent than tigolaner against P. xylostella. Molecular docking and DFT calculations suggested that additional predicted contacts involving Gln96 and Val126, together with a narrower HOMO\u2013LUMO gap, may contribute to the observed structure\u2013activity relationship. These calculations do not establish receptor affinity, and direct functional validation of GABAR antagonism remains necessary. FM-2665 therefore represents a promising lead for further optimization and safety evaluation.<\/jats:p>","DOI":"10.1021\/acs.jafc.5c17908","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T09:01:20Z","timestamp":1786006880000},"page":"25154-25163","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of\n                    <b>FM-2665<\/b>\n                    as a Potent Arylpyrazole\nInsecticidal and Acaricidal Candidate: Rational Design via Pyridine\nBioisosterism and Terminal Alkyl Optimization"],"prefix":"10.1021","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9840-0817","authenticated-orcid":true,"given":"Xiaowen","family":"Du","sequence":"first","affiliation":[{"name":"Shenyang University of Chemical Technology , , ,","place":["Shenyang, China, 110142"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongdong","family":"Liu","sequence":"additional","affiliation":[{"name":"Shenyang University of Chemical Technology , , ,","place":["Shenyang, China, 110142"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingjie","family":"Bi","sequence":"additional","affiliation":[{"name":"Shenyang University of Chemical Technology , , ,","place":["Shenyang, China, 110142"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4952-3550","authenticated-orcid":true,"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shenyang University of Chemical Technology , , ,","place":["Shenyang, China, 110142"]},{"name":"Metisa Biotechnology Co., Ltd. , ,","place":["Nanning, China, 530000"]},{"name":"University of Science and Technology Liaoning , , , ,","place":["Anshan, Liaoning, China, 114051"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shenyang University of Chemical Technology , , ,","place":["Shenyang, China, 110142"]},{"name":"Metisa Biotechnology Co., Ltd. , ,","place":["Nanning, China, 530000"]},{"name":"University of Science and Technology Liaoning , , , ,","place":["Anshan, Liaoning, China, 114051"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"issue":"1","key":"2026081910141959500_cit1","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1186\/s12870-025-07377-x","article-title":"Deep learning technique for plant disease classification\nand pest detection and model explainability elevating agricultural\nsustainability","volume":"25","author":"Shafik","year":"2025","journal-title":"BMC Plant Biol."},{"issue":"22","key":"2026081910141959500_cit2","doi-asserted-by":"publisher","first-page":"4116","DOI":"10.3390\/molecules24224116","article-title":"Identification of the\nfipronil resistance associated mutations in Nilaparvata lugens GABA receptors by molecular modeling","volume":"24","author":"Tian","year":"2019","journal-title":"Molecules"},{"issue":"6","key":"2026081910141959500_cit3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1010814","article-title":"G3\u2032M TMD3 in\nthe insect GABA receptor subunit, RDL, confers resistance to broflanilide\nand fluralaner","volume":"19","author":"Zhang","year":"2023","journal-title":"PLoS Genet."},{"issue":"4","key":"2026081910141959500_cit4","doi-asserted-by":"publisher","first-page":"1798","DOI":"10.1093\/jme\/tjab040","article-title":"Resistance to fipronil\nin the common bed bug","volume":"58","author":"Gonza\u0301lez-Morales","year":"2021","journal-title":"J. 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