{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T01:51:27Z","timestamp":1782611487114,"version":"3.54.5"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Tumor metastasis, a hallmark of advanced cancer, depends on integrin\u2010mediated adhesion and migration. Disintegrins, RGD\u2010containing peptides from snake venom, are potent integrin antagonists with antimetastatic potential. This study characterizes GbvIV4, a novel disintegrin (70 amino acids, RGD motif, MW: 7.44\u2009kDa) isolated from\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Gloydius brevicaudus<\/jats:italic>\n                    <\/jats:styled-content>\n                    venom, and its effects on melanoma progression. GbvIV4 exhibited high affinity for integrins \u03b1IIb\u03b23 (KD\u2009=\u20091.23\u2009\u03bcM) and \u03b1v\u03b23 (KD\u2009=\u2009650\u2009nM) and inhibited ADP\u2010induced platelet aggregation (IC50\u2009\u2248\u20091.34\u2009\u03bcg\/mL). In\u00a0vitro, GbvIV4 significantly suppressed B16\/B16\u2010F10 melanoma cell adhesion, migration, and invasion (~61% inhibition at 4\u2009\u03bcg\/mL). In\u00a0vivo, GbvIV4 (3.6\u2009mg\/kg, iv) reduced tumor weight by 49.5% (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05) and impaired angiogenesis, as shown by reduced vessel perfusion using laser speckle contrast imaging. Quantitative proteomics identified ATP\/GTP\u2010binding protein\u2010like 2 (AGBL2) as the most downregulated protein in GbvIV4\u2010treated cells, confirmed by RT\u2010PCR and western blot. Collectively, GbvIV4 exerts strong antimetastatic and antiangiogenic effects through dual mechanisms: inhibition of RGD\u2010binding integrins including but not limited to \u03b1IIb\u03b23\/\u03b1v\u03b23. GbvIV4 significantly downregulated AGBL2 expression and reduced the level of detyrosinated (glu\u2010) tubulin, indicating inhibition of AGBL2\u2010mediated tubulin detyrosination. These findings suggest GbvIV4 as a promising therapeutic candidate for melanoma treatment and metastasis prevention.\n                  <\/jats:p>","DOI":"10.1002\/jat.4990","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T05:56:35Z","timestamp":1764136595000},"page":"1951-1962","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Effect and Its Mechanism of a Novel Disintegrin GbvIV4 From\n                    <scp>\n                      <i>Gloydius brevicaudus<\/i>\n                    <\/scp>\n                    Venom on Inhibition Metastasis of Melanoma Cells"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8533-0847","authenticated-orcid":false,"given":"Jiayi","family":"Zhou","sequence":"first","affiliation":[{"name":"Fujian Provincial Key Laboratory on Hematology Fujian Medical University Affiliated Union Hospital, Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Pharmacy Fujian Medical University  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Peng","sequence":"additional","affiliation":[{"name":"Immunotherapy Institute Fujian Medical University  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningning","family":"Zhao","sequence":"additional","affiliation":[{"name":"Laboratory Animal Center Fujian Medical University  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhexi","family":"Xu","sequence":"additional","affiliation":[{"name":"Third Clinical College Henan Medical University  Xinxiang Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2057-6010","authenticated-orcid":false,"given":"Yunlu","family":"Xu","sequence":"additional","affiliation":[{"name":"Center of Translational Hematology Fujian Medical University  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2021.174022"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389203716666150515125002"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/194927b0"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2748"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.2474"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.11.001"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010018\u20100038\u2010z"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0092\u20108674(00)81683\u20109"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2019.10829"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)47710-1"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2004.08.001"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10930-024-10198-w"},{"key":"e_1_2_10_15_1","first-page":"497","article-title":"The Role and Mechanism of ABL2 in Lung Cancer","author":"Li C.","year":"2019","journal-title":"Practical Oncology Journal"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e37086"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2011.02.014"},{"key":"e_1_2_10_18_1","first-page":"897","article-title":"Isolation of a Novel Disintegrin Containing Arg\u2010Gly\u2010Asp Tripeptide Sequence From Gloydius brevicaudus Venom and Investigation of Its Biological Activities","volume":"12","author":"Lu\u2010Lin K. E.","year":"2019","journal-title":"Yao Xue Xue Bao"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.Ccr\u201007\u20105270"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12957\u2010020\u201002001\u20108"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2018.08.003"},{"issue":"4","key":"e_1_2_10_22_1","first-page":"289","article-title":"Disintegrins and Other Naturally Occurring Antagonists of Platelet Fibrinogen Receptors","volume":"31","author":"Niewiarowski S.","year":"1994","journal-title":"Seminars in Hematology"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.4544"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010022\u201001259\u20106"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416\u2010020\u20100798\u20106"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2016.04.008"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014\u20104827(91)90449\u20105"},{"issue":"1","key":"e_1_2_10_28_1","first-page":"11","article-title":"Echistatin Inhibits the Adhesion of Murine Melanoma Cells to Extracellular Matrix Components","volume":"35","author":"Staiano N.","year":"1995","journal-title":"Biochemistry and Molecular Biology International"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14010006"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.09.024"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2017.11.003"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477\u20107819\u201012\u2010142"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.4990","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jat.4990","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.4990","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T03:15:03Z","timestamp":1777864503000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.4990"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,25]]},"references-count":31,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/jat.4990"],"URL":"https:\/\/doi.org\/10.1002\/jat.4990","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,25]]},"assertion":[{"value":"2025-09-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}