{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T06:04:05Z","timestamp":1769580245360,"version":"3.49.0"},"reference-count":49,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,4,9]],"date-time":"2019-04-09T00:00:00Z","timestamp":1554768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201011\u2010LABX\u20100015"],"award-info":[{"award-number":["ANR\u201011\u2010LABX\u20100015"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>The Na<jats:sub>V<\/jats:sub>1.7 channel is highly expressed in dorsal root ganglia of the sensory nervous system and plays a central role in the pain signalling process. We investigated a library prepared from original venoms of 117 different animals to identify new selective inhibitors of this target.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We used high throughput screening of a large venom collection using automated patch\u2010clamp experiments on human voltage\u2010gated sodium channel subtypes and then in vitro and in vivo electrophysiological experiments to characterize the active peptides that have been purified, sequenced, and chemically synthesized. Analgesic effects were evaluated in vivo in mice models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>We identified cyriotoxin\u20101a (CyrTx\u20101a), a novel peptide isolated from <jats:styled-content style=\"fixed-case\"><jats:italic>Cyriopagopus schioedtei<\/jats:italic><\/jats:styled-content> spider venom, as a candidate for further characterization. This 33 amino acids toxin belongs to the inhibitor cystine knot structural family and inhibits hNa<jats:sub>V<\/jats:sub>1.1\u20131.3 and 1.6\u20131.7 channels in the low nanomolar range, compared to the micromolar range for hNa<jats:sub>V<\/jats:sub>1.4\u20131.5 and 1.8 channels. CyrTx\u20101a was 920 times more efficient at inhibiting tetrodotoxin (TTX)\u2010sensitive than TTX\u2010resistant sodium currents recorded from adult mouse dorsal root ganglia neurons and in vivo electrophysiological experiments showed that CyrTx\u20101a was approximately 170 times less efficient than huwentoxin\u2010IV at altering mouse skeletal neuromuscular excitability properties. CyrTx\u20101a exhibited an analgesic effect in mice by increasing reaction time in the hot\u2010plate assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>The pharmacological profile of CyrTx\u20101a paves the way for further molecular engineering aimed to optimize the potential antinociceptive properties of this peptide.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14628","type":"journal-article","created":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T03:21:07Z","timestamp":1550632867000},"page":"1298-1314","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["From identification to functional characterization of cyriotoxin\u20101a, an antinociceptive toxin from the spider <scp><i>Cyriopagopus schioedtei<\/i><\/scp>"],"prefix":"10.1111","volume":"176","author":[{"given":"T\u00e2nia C.","family":"Gon\u00e7alves","sequence":"first","affiliation":[{"name":"Integrated Drug Discovery\u2014High Content Biology Sanofi R&amp;D  Vitry\u2010sur\u2010Seine France"},{"name":"Service d'Ing\u00e9nierie Mol\u00e9culaire des Prot\u00e9ines (SIMOPRO), CEA Universit\u00e9 Paris\u2010Saclay  Gif\u2010sur\u2010Yvette France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5501-0888","authenticated-orcid":false,"given":"Evelyne","family":"Benoit","sequence":"additional","affiliation":[{"name":"Service d'Ing\u00e9nierie Mol\u00e9culaire des Prot\u00e9ines (SIMOPRO), CEA Universit\u00e9 Paris\u2010Saclay  Gif\u2010sur\u2010Yvette France"},{"name":"Institut des Neurosciences Paris\u2010Saclay (Neuro\u2010PSI), UMR CNRS\/Universit\u00e9 Paris\u2010Sud 9197 Universit\u00e9 Paris\u2010Saclay  Gif\u2010sur\u2010Yvette France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Kurz","sequence":"additional","affiliation":[{"name":"Integrated Drug Discovery\u2014Synthetic Molecular Design Sanofi R&amp;D  Frankfurt Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laetitia","family":"Lucarain","sequence":"additional","affiliation":[{"name":"Integrated Drug Discovery\u2014High Content Biology Sanofi R&amp;D  Vitry\u2010sur\u2010Seine France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Fouconnier","sequence":"additional","affiliation":[{"name":"Integrated Drug Discovery\u2014High Content Biology Sanofi R&amp;D  Vitry\u2010sur\u2010Seine France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"St\u00e9phanie","family":"Combemale","sequence":"additional","affiliation":[{"name":"Smartox Biotechnology  Saint\u2010Egr\u00e8ve France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucie","family":"Jaquillard","sequence":"additional","affiliation":[{"name":"Smartox Biotechnology  Saint\u2010Egr\u00e8ve France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brigitte","family":"Schombert","sequence":"additional","affiliation":[{"name":"Integrated Drug Discovery\u2014High Content Biology Sanofi R&amp;D  Vitry\u2010sur\u2010Seine France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean\u2010Marie","family":"Chambard","sequence":"additional","affiliation":[{"name":"Integrated Drug Discovery\u2014High Content Biology Sanofi R&amp;D  Vitry\u2010sur\u2010Seine France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachid","family":"Boukaiba","sequence":"additional","affiliation":[{"name":"Integrated Drug Discovery\u2014High Content Biology Sanofi R&amp;D  Vitry\u2010sur\u2010Seine France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerhard","family":"Hessler","sequence":"additional","affiliation":[{"name":"Integrated Drug Discovery\u2014Synthetic Molecular Design Sanofi R&amp;D  Frankfurt Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrees","family":"Bohme","sequence":"additional","affiliation":[{"name":"Integrated Drug Discovery\u2014High Content Biology Sanofi R&amp;D  Vitry\u2010sur\u2010Seine France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurent","family":"Bialy","sequence":"additional","affiliation":[{"name":"Integrated Drug Discovery\u2014Synthetic Molecular Design Sanofi R&amp;D  Frankfurt Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"St\u00e9phane","family":"Hourcade","sequence":"additional","affiliation":[{"name":"Neuroscience Therapeutic Area, Neurodegeneration Research Sanofi R&amp;D  Chilly\u2010Mazarin France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R\u00e9my","family":"B\u00e9roud","sequence":"additional","affiliation":[{"name":"Smartox Biotechnology  Saint\u2010Egr\u00e8ve France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"De Waard","sequence":"additional","affiliation":[{"name":"Smartox Biotechnology  Saint\u2010Egr\u00e8ve France"},{"name":"Institut du Thorax, Inserm UMR 1087\/CNRS UMR 6291 LabEx \u201cIon Channels, Science and Therapeutics\u201d  Nantes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0774-1691","authenticated-orcid":false,"given":"Denis","family":"Servent","sequence":"additional","affiliation":[{"name":"Service d'Ing\u00e9nierie Mol\u00e9culaire des Prot\u00e9ines (SIMOPRO), CEA Universit\u00e9 Paris\u2010Saclay  Gif\u2010sur\u2010Yvette France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Partiseti","sequence":"additional","affiliation":[{"name":"Integrated Drug Discovery\u2014High Content Biology Sanofi R&amp;D  Vitry\u2010sur\u2010Seine France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,4,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins9080248"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13884"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70024-9"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2014.09.005"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.090034797"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0278-5846(94)90084-1"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.115.098178"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13865"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13962"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.57.4.4"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-16-0326"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-013-1192-z"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1600418113"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2016.03.009"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins8030078"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3404"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep39662"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105895"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.01000"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2018.02.016"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/7212713"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apha.2017.01.004"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/123.12.2542"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2014.02.008"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.115.100784"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2012.04.337"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2008.00155.x"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm501981g"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405765200"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/psc.2451"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.426627"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-003-2354-x"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.461392"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3360"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0196791"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm501765v"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b01947"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17976"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204063200"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.121483"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins2122851"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b18-00054"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.725978"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2016.11.015"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3602"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708447200"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.110.066332"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.14628","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.14628","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.14628","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.14628","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T18:19:26Z","timestamp":1694369966000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.14628"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,9]]},"references-count":49,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["10.1111\/bph.14628"],"URL":"https:\/\/doi.org\/10.1111\/bph.14628","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,9]]},"assertion":[{"value":"2018-07-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}