{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:23:33Z","timestamp":1792859013234,"version":"4.5.0"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2017,7,1]],"date-time":"2017-07-01T00:00:00Z","timestamp":1498867200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["MCB-09020212"],"award-info":[{"award-number":["MCB-09020212"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"EC | European Regional Development Fund","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Prior to characterization of antifungal inhibitors that target CYP51,\n            <jats:named-content content-type=\"genus-species\">Trichophyton rubrum<\/jats:named-content>\n            CYP51 was expressed in\n            <jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>\n            , purified, and characterized.\n            <jats:named-content content-type=\"genus-species\">T. rubrum<\/jats:named-content>\n            CYP51 bound lanosterol, obtusifoliol, and eburicol with similar affinities (dissociation constant [\n            <jats:italic>\n              K\n              <jats:sub>d<\/jats:sub>\n            <\/jats:italic>\n            ] values, 22.7, 20.3, and 20.9 \u03bcM, respectively) but displayed substrate specificity, insofar as only eburicol was demethylated in CYP51 reconstitution assays (turnover number, 1.55 min\n            <jats:sup>\u22121<\/jats:sup>\n            ;\n            <jats:italic>\n              K\n              <jats:sub>m<\/jats:sub>\n            <\/jats:italic>\n            value, 2 \u03bcM). The investigational agent VT-1161 bound tightly to\n            <jats:named-content content-type=\"genus-species\">T. rubrum<\/jats:named-content>\n            CYP51 (\n            <jats:italic>\n              K\n              <jats:sub>d<\/jats:sub>\n            <\/jats:italic>\n            = 242 nM) with an affinity similar to that of clotrimazole, fluconazole, ketoconazole, and voriconazole (\n            <jats:italic>\n              K\n              <jats:sub>d<\/jats:sub>\n            <\/jats:italic>\n            values, 179, 173, 312, and 304 nM, respectively) and with an affinity lower than that of itraconazole (\n            <jats:italic>\n              K\n              <jats:sub>d<\/jats:sub>\n            <\/jats:italic>\n            = 53 nM). Determinations of 50% inhibitory concentrations (IC\n            <jats:sub>50<\/jats:sub>\n            s) using 0.5 \u03bcM CYP51 showed that VT-1161 was a tight-binding inhibitor of\n            <jats:named-content content-type=\"genus-species\">T. rubrum<\/jats:named-content>\n            CYP51 activity, yielding an IC\n            <jats:sub>50<\/jats:sub>\n            of 0.14 \u03bcM, whereas itraconazole, fluconazole, and ketoconazole had IC\n            <jats:sub>50<\/jats:sub>\n            s of 0.26, 0.4, and 0.6 \u03bcM, respectively. When the activity of VT-1161 was tested against 34 clinical isolates, VT-1161 was a potent inhibitor of\n            <jats:named-content content-type=\"genus-species\">T. rubrum<\/jats:named-content>\n            growth, with MIC\n            <jats:sub>50<\/jats:sub>\n            , MIC\n            <jats:sub>90<\/jats:sub>\n            , and geometric mean MIC values of \u22640.03, 0.06, and 0.033 \u03bcg ml\n            <jats:sup>\u22121<\/jats:sup>\n            , respectively. With its selectivity versus human CYP51 and drug-metabolizing cytochrome P450s having already been established, VT-1161 should prove to be safe and effective in combating\n            <jats:named-content content-type=\"genus-species\">T. rubrum<\/jats:named-content>\n            infections in patients.\n          <\/jats:p>","DOI":"10.1128\/aac.00333-17","type":"journal-article","created":{"date-parts":[[2017,5,9]],"date-time":"2017-05-09T00:40:16Z","timestamp":1494290416000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["The Tetrazole VT-1161 Is a Potent Inhibitor of Trichophyton rubrum through Its Inhibition of T. rubrum CYP51"],"prefix":"10.1128","volume":"61","author":[{"given":"Andrew G. S.","family":"Warrilow","sequence":"first","affiliation":[{"name":"Centre for Cytochrome P450 Biodiversity, Institute of Life Science, Swansea University Medical School, Swansea, Wales, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josie E.","family":"Parker","sequence":"additional","affiliation":[{"name":"Centre for Cytochrome P450 Biodiversity, Institute of Life Science, Swansea University Medical School, Swansea, Wales, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire L.","family":"Price","sequence":"additional","affiliation":[{"name":"Centre for Cytochrome P450 Biodiversity, Institute of Life Science, Swansea University Medical School, Swansea, Wales, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward P.","family":"Garvey","sequence":"additional","affiliation":[{"name":"Viamet Pharmaceuticals, Inc., Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Hoekstra","sequence":"additional","affiliation":[{"name":"Viamet Pharmaceuticals, Inc., Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Schotzinger","sequence":"additional","affiliation":[{"name":"Viamet Pharmaceuticals, Inc., Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan P.","family":"Wiederhold","sequence":"additional","affiliation":[{"name":"Fungus Testing Laboratory, Department of Pathology, and South Texas Reference Laboratories, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. David","family":"Nes","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane E.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Centre for Cytochrome P450 Biodiversity, Institute of Life Science, Swansea University Medical School, Swansea, Wales, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven L.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Centre for Cytochrome P450 Biodiversity, Institute of Life Science, Swansea University Medical School, Swansea, Wales, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.8.2.240"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0507.1989.tb02192.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0507.1995.tb00482.x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/13693780500536893"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.38.12.4527-4534.2000"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11046-008-9100-9"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof1020211"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/842917"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof2010004"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.2165\/00128071-200607010-00004"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.2165\/00128071-200203010-00003"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.3109\/1040841X.2013.856853"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-1097.2010.00848.x"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200262070-00004"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl377"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0507.2007.01325.x"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1567-1364.2010.00692.x"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2014.05.068"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03707-14"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4757-0196-8_9"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.16.8937"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(78)52029-6"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.03965-14"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00836a049"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2008.10.012"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2744(69)90420-3"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2010.06.006"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2010.01.075"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01806-15"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00349-16"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep27690"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00587-10"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01332-10"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M510317200"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi048967t"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.237099"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2006.08.007"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.32.558"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.106.013888"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4612-3730-3_11"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(87)90694-0"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000651"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mycres.2006.08.006"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-006-0731-8"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2230.2007.02480.x"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2012.05.070"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04902-14"},{"key":"e_1_3_3_49_2","volume-title":"Efficacy and safety of oral VT-1161, a novel and selective inhibitor of fungal CYP51, in a randomized, double-blind, placebo-controlled phase 2 study (NCT01891305) in patients with moderate-to-severe interdigital tinea pedis","author":"Degenhardt T","year":"2015","unstructured":"Degenhardt T PollakR JonesT JarrattM BrandtS SchotzingerR. 2015. Efficacy and safety of oral VT-1161, a novel and selective inhibitor of fungal CYP51, in a randomized, double-blind, placebo-controlled phase 2 study (NCT01891305) in patients with moderate-to-severe interdigital tinea pedis. Abstr Am Podiatr Med Assoc 2015 Annu Meet, Orlando, FL."},{"key":"e_1_3_3_50_2","volume-title":"A randomized, double-blind, placebo-controlled clinical trial of four oral dosing regimens of VT-1161 in the treatment of patients with moderate-severe toenail onychomycosis (RENOVATE): results of a planned week 24 interim analysis, poster 142","author":"Tavakkol A","year":"2016","unstructured":"Tavakkol A PollakR ReyzelmanA WeisfeldM CurelopA HandelsmanC BrandS DegenhardtT SchotzingerR. 2016. A randomized, double-blind, placebo-controlled clinical trial of four oral dosing regimens of VT-1161 in the treatment of patients with moderate-severe toenail onychomycosis (RENOVATE): results of a planned week 24 interim analysis, poster 142. Abstr Am Podiatr Med Assoc 2016 Annu Meet, Philadelphia, PA."},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.13.5597"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.03.067"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)82245-5"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0061(19990630)15:9<755::AID-YEA417>3.0.CO;2-8"},{"key":"e_1_3_3_55_2","first-page":"178","volume-title":"Evaluation of enzyme inhibitors in drug discovery: a guide for medicinal chemists and pharmacologists","author":"Copeland RA","year":"2005","unstructured":"Copeland RA . 2005. Evaluation of enzyme inhibitors in drug discovery: a guide for medicinal chemists and pharmacologists, p 178\u2013213. Wiley-Interscience, New York, NY."},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2007.10.011"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.03246-12"},{"key":"e_1_3_3_58_2","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/0471220639","volume-title":"Enzymes: a practical introduction to structure, mechanism and data analysis","author":"Copeland RA","year":"2000","unstructured":"Copeland RA . 2000. Enzymes: a practical introduction to structure, mechanism and data analysis, 2nd ed, p 137. Wiley-VCH Inc, New York, NY.","edition":"2"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00333-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00333-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T21:07:33Z","timestamp":1645477653000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00333-17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7]]},"references-count":57,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2017,7]]}},"alternative-id":["10.1128\/AAC.00333-17"],"URL":"https:\/\/doi.org\/10.1128\/aac.00333-17","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7]]},"assertion":[{"value":"2017-02-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-04-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-06-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00333-17"}}