{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:45:07Z","timestamp":1787013907721,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["310968\/2023\u20102"],"award-info":[{"award-number":["310968\/2023\u20102"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["APQ\u201003767\u201023"],"award-info":[{"award-number":["APQ\u201003767\u201023"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["RED00097\u201021"],"award-info":[{"award-number":["RED00097\u201021"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["APQ\u201002045\u201024"],"award-info":[{"award-number":["APQ\u201002045\u201024"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["APQ\u201000842\u201023"],"award-info":[{"award-number":["APQ\u201000842\u201023"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["APQ\u201006532\u201024"],"award-info":[{"award-number":["APQ\u201006532\u201024"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Ph\u03b11\u03b2 is a peptide toxin originally isolated from the venom of the Brazilian spider\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Phoneutria nigriventer<\/jats:italic>\n                    <\/jats:styled-content>\n                    , known for its potent analgesic effects in preclinical models of acute and chronic pain. However, clinical translation has been limited by production constraints. A recombinant analogue, CTK01512\u20102, was developed and has demonstrated antinociceptive efficacy comparable to the native toxin in diverse experimental models. In this study, we examined the effects of CTK01512\u20102 on N\u2010type voltage\u2010gated calcium channels (Cav2.2) expressed in transiently transfected HEK\u2010293 cells and confirmed its antinociceptive action in a mouse model of neuropathic pain. CTK01512\u20102 induced a partial (~50%) and reversible inhibition of Cav2.2\u2010mediated calcium currents, with a calculated half\u2010maximal inhibitory concentration (IC\n                    <jats:sub>50<\/jats:sub>\n                    ) of 3.94\u2009nM. In contrast to \u03c9\u2010conotoxin MVIIA, a clinically approved irreversible Cav2.2 blocker, CTK01512\u20102 allowed current recovery after washout, indicating reversible binding. Notably, the toxin did not significantly alter the voltage dependence or kinetics of channel activation. These findings identify CTK01512\u20102 as a selective and reversible Cav2.2 channel modulator, underscoring its therapeutic potential as a novel analgesic agent for chronic pain management.\n                  <\/jats:p>","DOI":"10.1111\/bcpt.70268","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T15:31:02Z","timestamp":1782919862000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacological Inhibition of Cav2.2 Channels by Recombinant Ph\u03b11\u03b2 Toxin (CTK01512\u20102)"],"prefix":"10.1111","volume":"139","author":[{"given":"Nat\u00e1lia Virtude","family":"Carobin","sequence":"first","affiliation":[{"name":"Faculdade de Sa\u00fade Santa Casa BH  Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thamyris Reis","family":"Moraes","sequence":"additional","affiliation":[{"name":"Faculdade de Sa\u00fade Santa Casa BH  Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana Assis","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Psychological &amp; Brain Science Indiana University  Bloomington Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5251-3025","authenticated-orcid":false,"given":"Christopher","family":"Kushmerick","sequence":"additional","affiliation":[{"name":"Departamento de Fisiologia Universidade Federal de Sergipe  S\u00e3o Crist\u00f3v\u00e3o Sergipe Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus Vin\u00edcius","family":"Gomez","sequence":"additional","affiliation":[{"name":"Faculdade de Sa\u00fade Santa Casa BH  Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9lio Jos\u00e9 Castro","family":"Junior","sequence":"additional","affiliation":[{"name":"Faculdade de Sa\u00fade Santa Casa BH  Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041\u20100101(93)90354\u2010l"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571\u2010012\u20109871\u2010x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1590\/1678\u20109199\u2010JVATITD\u20102021\u20100001"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2008.07.014"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2017.05.018"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173672"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43440\u2010020\u201000108\u2010z"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43440\u2010019\u201000002\u20103"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2021.03.012"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1590\/1678\u20109199\u2010JVATITD\u20102019\u20100070"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.087023"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.09.028"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.07.016"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.10.2349"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.291.1.63"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.13.7.875"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.70159"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787\u2010020\u201000756\u2010w"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304\u20103959(88)90209\u20106"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1848"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2643"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010024\u201000763\u20107"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2024.102568"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/md15100313"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00317a001"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1993.2225"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2008.05.019"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701381"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201801909R"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbt.2019.02.004"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13361\u2010018\u20101904\u20103"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1994.1026"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1023\/b:jobb.0000008022.50702.1a"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.20028560"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16\u201008\u201002612.1996"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708447200"},{"key":"e_1_2_9_38_1","volume-title":"Ion Channels of Excitable Membranes","author":"Hille B.","year":"2001"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(25)38848-8"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304\u20103959(94)00094\u2010U"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0304\u20103959(99)00197\u20109"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1590\/1678\u20109199\u2010JVATITD\u20102024\u20100039"}],"container-title":["Basic &amp; Clinical Pharmacology &amp; Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcpt.70268","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bcpt.70268","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcpt.70268","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T03:28:47Z","timestamp":1784690927000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bcpt.70268"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":41,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1111\/bcpt.70268"],"URL":"https:\/\/doi.org\/10.1111\/bcpt.70268","archive":["Portico"],"relation":{},"ISSN":["1742-7835","1742-7843"],"issn-type":[{"value":"1742-7835","type":"print"},{"value":"1742-7843","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]},"assertion":[{"value":"2025-07-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70268"}}