{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:20:58Z","timestamp":1781104858750,"version":"3.54.1"},"reference-count":66,"publisher":"National Academy of Sciences","issue":"45","license":[{"start":{"date-parts":[[2019,4,24]],"date-time":"2019-04-24T00:00:00Z","timestamp":1556064000000},"content-version":"vor","delay-in-days":182,"URL":"http:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2018,11,6]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Voltage-gated ion channels, such as Ca\n                    <jats:sub>V<\/jats:sub>\n                    2.2, consist of pore-forming and auxiliary subunits that interact through protein\u2013protein interactions. We develop a small-molecule antagonist of the protein\u2013protein interaction between the calcium channel alpha pore-forming domain (Ca\n                    <jats:sub>V<\/jats:sub>\n                    \u03b1) and beta subunits (Ca\n                    <jats:sub>V<\/jats:sub>\n                    \u03b2). The compound suppresses trafficking of Ca\n                    <jats:sub>V<\/jats:sub>\n                    2.2 channels to the cell membrane and inhibits Ca\n                    <jats:sub>V<\/jats:sub>\n                    2.2 activity by acting intracellularly. This allows peripheral access and eliminates the need of intrathecal administration. Indeed, in vivo systemic administration of the small molecule reduces neuropathic pain behavior in animal models. Our compounds serve as chemical tools to explore the Ca\n                    <jats:sub>V<\/jats:sub>\n                    \u03b1\u22c5Ca\n                    <jats:sub>V<\/jats:sub>\n                    \u03b2 interaction in vivo and as a starting point for the development of therapeutics for the treatment of a range of disorders associated with calcium channels.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1813157115","type":"journal-article","created":{"date-parts":[[2018,10,24]],"date-time":"2018-10-24T16:45:21Z","timestamp":1540399521000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":22,"title":["Small-molecule Ca\n                    <sub>V<\/sub>\n                    \u03b1\n                    <sub>1<\/sub>\n                    \u22c5Ca\n                    <sub>V<\/sub>\n                    \u03b2 antagonist suppresses neuronal voltage-gated calcium-channel trafficking"],"prefix":"10.1073","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7380-8399","authenticated-orcid":false,"given":"Xingjuan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Degang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubing","family":"Si","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202;"},{"name":"Department of BioHealth Informatics, Indiana University School of Medicine, Indianapolis, IN 46202;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher W.","family":"Stamatkin","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202;"},{"name":"Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona K.","family":"Ghozayel","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew S.","family":"Ripsch","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Indiana University School of Medicine, Indianapolis, IN 46202;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3862-6004","authenticated-orcid":false,"given":"Alexander G.","family":"Obukhov","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202;"},{"name":"Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fletcher A.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Indiana University School of Medicine, Indianapolis, IN 46202;"},{"name":"Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samy O.","family":"Meroueh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202;"},{"name":"Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202;"},{"name":"Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2018,10,24]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-080411-121438"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.16.1.521"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1993.tb38038.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02110697"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4160(98)90055-0"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.17.030194.002151"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/BFb0033648"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706442"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(03)00066-7"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2004.03434.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature19321"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0307-07.2007"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568026054367610"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1159\/000079056"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0356-09.2009"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.114.009654"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(97)00196-2"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2009.06.006"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2004.10.008"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02588"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2001.85.2.816"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2007.11.010"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.109744"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303564200"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(01)75799-2"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2014.06.003"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.202485799"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7529940"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.10.077"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1998.1843"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(03)00610-7"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/ci200322s"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06526"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201412070"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2015.04.019"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2014.09.001"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr4004049"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb300255p"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2014.09.047"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.1568"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm0507532"},{"key":"e_1_3_3_42_2","first-page":"25","article-title":"Small-molecule inhibitors of IL-2\/IL-2R: Lessons learned and applied","volume":"348","author":"Wilson CG","year":"2011","unstructured":"CG Wilson, MR Arkin, Small-molecule inhibitors of IL-2\/IL-2R: Lessons learned and applied. Curr Top Microbiol Immunol 348, 25\u201359 (2011).","journal-title":"Curr Top Microbiol Immunol"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm501092z"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1747-0285.2007.00483.x"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1039\/C6MB00231E"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb200180m"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201510866"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.10.006"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1089\/adt.2011.0380"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201204268"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200308967"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2012.08.028"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-9-180"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0107399"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.4161\/chan.2.1.6045"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2006.04.010"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.44.101802.121627"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1998.2401"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2005.01.010"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00048.2004"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.755470"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.111.183673"},{"key":"e_1_3_3_64_2","volume-title":"Guide for the Care and Use of Laboratory Animals","author":"National Research Council","year":"2011","unstructured":"; National Research Council Guide for the Care and Use of Laboratory Animals (National Academies Press, 8th Ed, Washington, DC, 2011).","edition":"8"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000628"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-3-38"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1813157115","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T04:07:54Z","timestamp":1649822874000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1813157115"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,24]]},"references-count":66,"journal-issue":{"issue":"45","published-print":{"date-parts":[[2018,11,6]]}},"alternative-id":["10.1073\/pnas.1813157115"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1813157115","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.734291154.793555763","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,24]]},"assertion":[{"value":"2018-10-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}