{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:56:15Z","timestamp":1791507375502,"version":"4.3.4"},"reference-count":75,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2018,6,29]],"date-time":"2018-06-29T00:00:00Z","timestamp":1530230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB1089 SFB645"],"award-info":[{"award-number":["SFB1089 SFB645"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CRU326"],"award-info":[{"award-number":["CRU326"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SPP1926, 1726 and TRR83"],"award-info":[{"award-number":["SPP1926, 1726 and TRR83"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB1089"],"award-info":[{"award-number":["SFB1089"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB645"],"award-info":[{"award-number":["SFB645"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008454","name":"Boehringer Ingelheim Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008454","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FF\u20102016\u201017"],"award-info":[{"award-number":["FF\u20102016\u201017"]}],"id":[{"id":"10.13039\/501100001659","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":[[2018,8]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Sperm from many species share the sperm\u2010specific Ca<jats:sup>2+<\/jats:sup> channel CatSper that controls the intracellular Ca<jats:sup>2+<\/jats:sup> concentration and, thereby, the swimming behaviour. A growing body of evidence suggests that the mechanisms controlling the activity of CatSper and its role during fertilization differ among species. A lack of suitable pharmacological tools has hampered the elucidation of the function of CatSper. Known inhibitors of CatSper exhibit considerable side effects and also inhibit Slo3, the principal K<jats:sup>+<\/jats:sup> channel of mammalian sperm. The compound RU1968 was reported to suppress Ca<jats:sup>2+<\/jats:sup> signaling in human sperm by an unknown mechanism. Here, we examined the action of RU1968 on CatSper in sperm from humans, mice, and sea urchins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We resynthesized RU1968 and studied its action on sperm from humans, mice, and the sea urchin <jats:italic>Arbacia punctulata<\/jats:italic> by Ca<jats:sup>2+<\/jats:sup> fluorimetry, single\u2010cell Ca<jats:sup>2+<\/jats:sup> imaging, electrophysiology, opto\u2010chemistry, and motility analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>RU1968 inhibited CatSper in sperm from invertebrates and mammals. The compound lacked toxic side effects in human sperm, did not affect mouse Slo3, and inhibited human Slo3 with about 15\u2010fold lower potency than CatSper. Moreover, in human sperm, RU1968 mimicked CatSper dysfunction and suppressed motility responses evoked by progesterone, an oviductal steroid known to activate CatSper. Finally, RU1968 abolished CatSper\u2010mediated chemotactic navigation in sea urchin sperm.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>We propose RU1968 as a novel tool to elucidate the function of CatSper channels in sperm across species.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14355","type":"journal-article","created":{"date-parts":[[2018,5,3]],"date-time":"2018-05-03T22:57:19Z","timestamp":1525388239000},"page":"3144-3161","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["A novel cross\u2010species inhibitor to study the function of CatSper Ca<sup>2+<\/sup> channels in sperm"],"prefix":"10.1111","volume":"175","author":[{"given":"Andreas","family":"Rennhack","sequence":"first","affiliation":[{"name":"Department of Molecular Sensory Systems Center of Advanced European Studies and Research (CAESAR)  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Schiffer","sequence":"additional","affiliation":[{"name":"University Hospital M\u00fcnster, Centre of Reproductive Medicine and Andrology  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Brenker","sequence":"additional","affiliation":[{"name":"University Hospital M\u00fcnster, Centre of Reproductive Medicine and Andrology  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Fridman","sequence":"additional","affiliation":[{"name":"Department of Molecular Sensory Systems Center of Advanced European Studies and Research (CAESAR)  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elis T","family":"Nitao","sequence":"additional","affiliation":[{"name":"School of Biosciences University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Min","family":"Cheng","sequence":"additional","affiliation":[{"name":"Institute of Life Science and School of Life Science Nanchang University  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Tamburrino","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Center of Excellence DENOTHE University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Balbach","sequence":"additional","affiliation":[{"name":"Department of Molecular Sensory Systems Center of Advanced European Studies and Research (CAESAR)  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2339-0545","authenticated-orcid":false,"given":"Gabriel","family":"St\u00f6lting","sequence":"additional","affiliation":[{"name":"Institute of Complex Systems \u2013 Zellul\u00e4re Biophysik 4, Forschungszentrum J\u00fclich  J\u00fclich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas K","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Molecular Sensory Systems Center of Advanced European Studies and Research (CAESAR)  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelina","family":"Kierzek","sequence":"additional","affiliation":[{"name":"University Hospital M\u00fcnster, Centre of Reproductive Medicine and Andrology  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Department of Molecular Sensory Systems Center of Advanced European Studies and Research (CAESAR)  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Wachten","sequence":"additional","affiliation":[{"name":"Max\u2010Planck Research Group of Molecular Physiology, Center of Advanced European Studies and Research  Bonn Germany"},{"name":"Institute of Innate Immunity University Hospital, University of Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu\u2010Hui","family":"Zeng","sequence":"additional","affiliation":[{"name":"Institute of Life Science and School of Life Science Nanchang University  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Baldi","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Center of Excellence DENOTHE University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J","family":"Publicover","sequence":"additional","affiliation":[{"name":"School of Biosciences University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U Benjamin","family":"Kaupp","sequence":"additional","affiliation":[{"name":"Department of Molecular Sensory Systems Center of Advanced European Studies and Research (CAESAR)  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0812-1547","authenticated-orcid":false,"given":"Timo","family":"Str\u00fcnker","sequence":"additional","affiliation":[{"name":"University Hospital M\u00fcnster, Centre of Reproductive Medicine and Andrology  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/des467"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.439356"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13884"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13879"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10265-017-0936-2"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201106096"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2013.10.004"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(01)99290-7"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(01)90870-6"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.03.004"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2009.02.006"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600744"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2012.30"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.01438"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1717929115"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003569"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msu218"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006844"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501430200"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2536658100"},{"key":"e_1_2_10_22_1","article-title":"Acrosomal alkalization triggers Ca2+ release and acrosome reaction in mammalian spermatozoa","author":"Ch\u00e1vez JC","year":"2017","journal-title":"J Cell Physiol"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.23082"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1153"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.02.056"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14153"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-03857-9"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.07624"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj20021560"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2010.108"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1071\/RD08183"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb915"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2016.10.002"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja808334f"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04417"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.12.053"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09767"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701083200"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.113.111708"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gau003"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0012-1606(03)00236-7"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12955"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2013.02.007"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad6887"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/254244a0"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/13.8.2139"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702018104"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1111695108"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/den265"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(78)90096-4"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.2741\/3105"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0610286104"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/35098027"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/35098027"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2010.02.005"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod63.1.57"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.6.3008"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201438869"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-108-2-457"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201489376"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09769"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmn029"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/det454"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dev103"},{"key":"e_1_2_10_67_1","first-page":"417","article-title":"Synthetic uses of tosylmethyl isocyanide (TosMic)","volume":"57","author":"Van Leusen D","year":"2004","journal-title":"Organic Reactions"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.109.077107"},{"key":"e_1_2_10_69_1","first-page":"2737","article-title":"Specific loss of CatSper function is sufficient to compromise fertilization capacity of human spermatozoa","volume":"30","author":"Williams HL","year":"2015","journal-title":"Hum Reprod"},{"key":"e_1_2_10_70_1","unstructured":"WHO (2010).World Health Organization Department of Reproductive Health and Research. WHO laboratory manual for the examination and processing of human semen fifth edition."},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/iox015"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14584"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.242470599"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep23553"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201311011"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1100240108"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.14355","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.14355","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T02:14:12Z","timestamp":1694312052000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.14355"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,29]]},"references-count":75,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2018,8]]}},"alternative-id":["10.1111\/bph.14355"],"URL":"https:\/\/doi.org\/10.1111\/bph.14355","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,29]]},"assertion":[{"value":"2017-05-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}