{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:54:58Z","timestamp":1792029298809,"version":"4.4.0"},"reference-count":49,"publisher":"Wiley","issue":"49","license":[{"start":{"date-parts":[[2015,10,12]],"date-time":"2015-10-12T00:00:00Z","timestamp":1444608000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Herein, we report the discovery of the first potent and selective inhibitor of TRPV6, a calcium channel overexpressed in breast and prostate cancer, and its use to test the effect of blocking TRPV6\u2010mediated Ca<jats:sup>2+<\/jats:sup>\u2010influx on cell growth. The inhibitor was discovered through a computational method, xLOS, a 3D\u2010shape and pharmacophore similarity algorithm, a type of ligand\u2010based virtual screening (LBVS) method described briefly here. Starting with a single weakly active seed molecule, two successive rounds of LBVS followed by optimization by chemical synthesis led to a selective molecule with 0.3\u2005\u03bc<jats:sc>M<\/jats:sc> inhibition of TRPV6. The ability of xLOS to identify different scaffolds early in LBVS was essential to success. The xLOS method may be generally useful to develop tool compounds for poorly characterized targets.<\/jats:p>","DOI":"10.1002\/anie.201507320","type":"journal-article","created":{"date-parts":[[2015,10,13]],"date-time":"2015-10-13T11:04:38Z","timestamp":1444734278000},"page":"14748-14752","source":"Crossref","is-referenced-by-count":58,"title":["Optimization of TRPV6 Calcium Channel Inhibitors Using a 3D Ligand\u2010Based Virtual Screening Method"],"prefix":"10.1002","volume":"54","author":[{"given":"C\u00e9line","family":"Simonin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahendra","family":"Awale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Brand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruud","family":"van\u2005Deursen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Fine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gergely","family":"Kovacs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"H\u00e4fliger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gergely","family":"Gyimesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abilashan","family":"Sithampari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roch\u2010Philippe","family":"Charles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias A.","family":"Hediger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Louis","family":"Reymond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,10,12]]},"reference":[{"key":"e_1_2_3_1_2","unstructured":"\u00a0"},{"key":"e_1_2_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2006.05.012"},{"key":"e_1_2_3_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/ci200528d"},{"key":"e_1_2_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.12054"},{"key":"e_1_2_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201307786"},{"key":"e_1_2_3_5_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201307786"},{"key":"e_1_2_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2014.07.007"},{"key":"e_1_2_3_7_2","unstructured":"\u00a0"},{"key":"e_1_2_3_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.32.22739"},{"key":"e_1_2_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/35070596"},{"key":"e_1_2_3_10_2","unstructured":"M. A.Hediger E. M.Brown J. B.Peng Patent US6534642 2003and US7078178 2006;"},{"key":"e_1_2_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/35077544"},{"key":"e_1_2_3_12_2","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-09-0188"},{"key":"e_1_2_3_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-54215-2_14"},{"key":"e_1_2_3_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-05161-1_10"},{"key":"e_1_2_3_15_2","unstructured":"\u00a0"},{"key":"e_1_2_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210545"},{"key":"e_1_2_3_17_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-07-0478"},{"key":"e_1_2_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1413409111"},{"key":"e_1_2_3_19_2","unstructured":"\u00a0"},{"key":"e_1_2_3_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-010-0249-9"},{"key":"e_1_2_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2012.08.005"},{"key":"e_1_2_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2013.03.037"},{"key":"e_1_2_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12823"},{"key":"e_1_2_3_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-342-8_1"},{"key":"e_1_2_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4163"},{"key":"e_1_2_3_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-3773(19991004)38:19<2894::AID-ANIE2894>3.0.CO;2-F"},{"key":"e_1_2_3_26_3","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-3757(19991004)111:19<3068::AID-ANGE3068>3.0.CO;2-0"},{"key":"e_1_2_3_27_2","unstructured":"\u00a0"},{"key":"e_1_2_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0898-5529(90)90162-2"},{"key":"e_1_2_3_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-006-9072-0"},{"key":"e_1_2_3_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm0603365"},{"key":"e_1_2_3_31_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13321-014-0051-5"},{"key":"e_1_2_3_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr00023a012"},{"key":"e_1_2_3_33_2","unstructured":"\u00a0"},{"key":"e_1_2_3_34_2","doi-asserted-by":"publisher","DOI":"10.1021\/ci050075s"},{"key":"e_1_2_3_35_2","doi-asserted-by":"publisher","DOI":"10.1021\/ci100263p"},{"key":"e_1_2_3_36_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm0608356"},{"key":"e_1_2_3_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/ci3001277"},{"key":"e_1_2_3_38_2","unstructured":"\u00a0"},{"key":"e_1_2_3_39_2","doi-asserted-by":"publisher","DOI":"10.1039\/C1MD00017A"},{"key":"e_1_2_3_40_2","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.11.46"},{"key":"e_1_2_3_41_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm901137j"},{"key":"e_1_2_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2010.11.007"},{"key":"e_1_2_3_43_2","unstructured":"\u00a0"},{"key":"e_1_2_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2006.10.005"},{"key":"e_1_2_3_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku379"},{"key":"e_1_2_3_46_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm800965b"},{"key":"e_1_2_3_47_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja202070j"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fanie.201507320","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.201507320","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.201507320","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.201507320","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T18:19:13Z","timestamp":1693678753000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.201507320"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,12]]},"references-count":49,"journal-issue":{"issue":"49","published-print":{"date-parts":[[2015,12]]}},"alternative-id":["10.1002\/anie.201507320"],"URL":"https:\/\/doi.org\/10.1002\/anie.201507320","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,12]]}}}