{"id":"https://openalex.org/W3029648668","doi":"https://doi.org/10.1093/mmy/myz092","title":"The novel fungal CYP51 inhibitor VT-1598 displays classic dose-dependent antifungal activity in murine models of invasive aspergillosis","display_name":"The novel fungal CYP51 inhibitor VT-1598 displays classic dose-dependent antifungal activity in murine models of invasive aspergillosis","publication_year":2019,"publication_date":"2019-08-22","ids":{"openalex":"https://openalex.org/W3029648668","doi":"https://doi.org/10.1093/mmy/myz092","mag":"3029648668","pmid":"https://pubmed.ncbi.nlm.nih.gov/32476008"},"language":"en","primary_location":{"id":"doi:10.1093/mmy/myz092","doi":"https://doi.org/10.1093/mmy/myz092","is_oa":false,"landing_page_url":"https://doi.org/10.1093/mmy/myz092","pdf_url":null,"source":{"id":"https://openalex.org/S93288122","display_name":"Medical Mycology","issn_l":"0268-1218","issn":["0268-1218","1365-280X","1369-3786","1460-2709"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-c","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-70","russia-white-list-1"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Medical Mycology","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5110166075","display_name":"Edward P. Garvey","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210151457","display_name":"Viamet Pharmaceuticals (United States)","ror":"https://ror.org/0511egv62","country_code":"US","type":"company","lineage":["https://openalex.org/I4210151457"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"E P Garvey","raw_affiliation_strings":["Viamet Pharmaceuticals, Inc., Durham, NC 27703"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Viamet Pharmaceuticals, Inc., Durham, NC 27703","institution_ids":["https://openalex.org/I4210151457"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5011598437","display_name":"Joanne Sharp","orcid":"https://orcid.org/0000-0001-8482-5736","observed_orcids":["https://orcid.org/0000-0001-8482-5736"]},"institutions":[{"id":"https://openalex.org/I4210148098","display_name":"Evotec (United Kingdom)","ror":"https://ror.org/04qvy9k41","country_code":"GB","type":"company","lineage":["https://openalex.org/I4210130816","https://openalex.org/I4210148098"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"A D Sharp","raw_affiliation_strings":["Evotec UK Ltd., Macclesfield, England"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Evotec UK Ltd., Macclesfield, England","institution_ids":["https://openalex.org/I4210148098"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5078573153","display_name":"Peter A. Warn","orcid":"https://orcid.org/0000-0002-0862-9714","observed_orcids":["https://orcid.org/0000-0002-0862-9714"]},"institutions":[{"id":"https://openalex.org/I4210148098","display_name":"Evotec (United Kingdom)","ror":"https://ror.org/04qvy9k41","country_code":"GB","type":"company","lineage":["https://openalex.org/I4210130816","https://openalex.org/I4210148098"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"P A Warn","raw_affiliation_strings":["Evotec UK Ltd., Macclesfield, England"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Evotec UK Ltd., Macclesfield, England","institution_ids":["https://openalex.org/I4210148098"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5083348242","display_name":"Christopher M. Yates","orcid":"https://orcid.org/0000-0003-0884-1122","observed_orcids":["https://orcid.org/0000-0003-0884-1122"]},"institutions":[{"id":"https://openalex.org/I4210151457","display_name":"Viamet Pharmaceuticals (United States)","ror":"https://ror.org/0511egv62","country_code":"US","type":"company","lineage":["https://openalex.org/I4210151457"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"C M Yates","raw_affiliation_strings":["Viamet Pharmaceuticals, Inc., Durham, NC 27703"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Viamet Pharmaceuticals, Inc., Durham, NC 27703","institution_ids":["https://openalex.org/I4210151457"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110446817","display_name":"Mohammed I. Atari","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"M Atari","raw_affiliation_strings":["Cyprotex Discovery Ltd. Macclesfield, England"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cyprotex Discovery Ltd. Macclesfield, England","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5021669399","display_name":"Simon Thomas","orcid":"https://orcid.org/0000-0002-9979-081X","observed_orcids":["https://orcid.org/0000-0002-9979-081X"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"S Thomas","raw_affiliation_strings":["Cyprotex Discovery Ltd. Macclesfield, England"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cyprotex Discovery Ltd. Macclesfield, England","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5073464082","display_name":"Robert J. Schotzinger","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210151457","display_name":"Viamet Pharmaceuticals (United States)","ror":"https://ror.org/0511egv62","country_code":"US","type":"company","lineage":["https://openalex.org/I4210151457"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"R J Schotzinger","raw_affiliation_strings":["Viamet Pharmaceuticals, Inc., Durham, NC 27703"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Viamet Pharmaceuticals, Inc., Durham, NC 27703","institution_ids":["https://openalex.org/I4210151457"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5110166075"],"corresponding_institution_ids":["https://openalex.org/I4210151457"],"apc_list":{"value":4889,"currency":"USD","value_usd":4889},"apc_paid":null,"fwci":1.341,"has_fulltext":false,"cited_by_count":20,"citation_normalized_percentile":{"value":0.80365629,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":99},"biblio":{"volume":"58","issue":"4","first_page":"505","last_page":"513"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10150","display_name":"Antifungal resistance and susceptibility","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2725","display_name":"Infectious Diseases"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10150","display_name":"Antifungal resistance and susceptibility","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2725","display_name":"Infectious Diseases"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11036","display_name":"Antibiotics Pharmacokinetics and Efficacy","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2736","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11037","display_name":"Fungal Infections and Studies","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2713","display_name":"Epidemiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/cyp51-inhibitors","display_name":"CYP51 inhibitors","score":0.859000027179718},{"id":"https://openalex.org/keywords/invasive-aspergillosis","display_name":"invasive aspergillosis","score":0.9559999704360962},{"id":"https://openalex.org/keywords/aspergillus-fumigatus","display_name":"Aspergillus fumigatus","score":0.9950000047683716},{"id":"https://openalex.org/keywords/pharmacokinetics","display_name":"pharmacokinetics","score":0.8489999771118164},{"id":"https://openalex.org/keywords/pharmacodynamics","display_name":"pharmacodynamics","score":0.996999979019165},{"id":"https://openalex.org/keywords/pk-pd-relationship","display_name":"PK/PD relationship","score":0.8840000033378601},{"id":"https://openalex.org/keywords/neutropenic-mouse-model","display_name":"neutropenic mouse model","score":0.7789999842643738},{"id":"https://openalex.org/keywords/disseminated-aspergillosis","display_name":"disseminated aspergillosis","score":0.8389999866485596},{"id":"https://openalex.org/keywords/pulmonary-aspergillosis","display_name":"pulmonary aspergillosis","score":0.9909999966621399},{"id":"https://openalex.org/keywords/antifungal-drug-development","display_name":"antifungal drug development","score":0.6010000109672546}],"concepts":[{"id":"https://openalex.org/C2779787849","wikidata":"https://www.wikidata.org/wiki/Q134359","display_name":"Aspergillus fumigatus","level":2,"score":0.7870486378669739},{"id":"https://openalex.org/C2776391196","wikidata":"https://www.wikidata.org/wiki/Q259626","display_name":"Aspergillosis","level":2,"score":0.7691924571990967},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.6530691981315613},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.6085783839225769},{"id":"https://openalex.org/C111113717","wikidata":"https://www.wikidata.org/wiki/Q725307","display_name":"Pharmacodynamics","level":3,"score":0.5871458053588867},{"id":"https://openalex.org/C2991737395","wikidata":"https://www.wikidata.org/wiki/Q578726","display_name":"Antifungal drug","level":3,"score":0.5115681290626526},{"id":"https://openalex.org/C2777071850","wikidata":"https://www.wikidata.org/wiki/Q411229","display_name":"Itraconazole","level":3,"score":0.4756481349468231},{"id":"https://openalex.org/C76318530","wikidata":"https://www.wikidata.org/wiki/Q16833590","display_name":"Area under the curve","level":2,"score":0.4565311670303345},{"id":"https://openalex.org/C2777288759","wikidata":"https://www.wikidata.org/wiki/Q4164182","display_name":"Dosing","level":2,"score":0.43854284286499023},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.4117496609687805},{"id":"https://openalex.org/C2779548794","wikidata":"https://www.wikidata.org/wiki/Q578726","display_name":"Antifungal","level":2,"score":0.3918599486351013},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.38129425048828125},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3387185335159302},{"id":"https://openalex.org/C89423630","wikidata":"https://www.wikidata.org/wiki/Q7193","display_name":"Microbiology","level":1,"score":0.31850916147232056},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.16856884956359863}],"mesh":[{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000935","descriptor_name":"Antifungal Agents","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D000935","descriptor_name":"Antifungal Agents","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D001232","descriptor_name":"Aspergillus fumigatus","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":true},{"descriptor_ui":"D004195","descriptor_name":"Disease Models, Animal","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004305","descriptor_name":"Dose-Response Relationship, Drug","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008826","descriptor_name":"Microbial Sensitivity Tests","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009503","descriptor_name":"Neutropenia","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011725","descriptor_name":"Pyridines","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D011725","descriptor_name":"Pyridines","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D013777","descriptor_name":"Tetrazoles","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D013777","descriptor_name":"Tetrazoles","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D051379","descriptor_name":"Mice","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D055744","descriptor_name":"Invasive Pulmonary Aspergillosis","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D058888","descriptor_name":"14-alpha Demethylase Inhibitors","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1093/mmy/myz092","doi":"https://doi.org/10.1093/mmy/myz092","is_oa":false,"landing_page_url":"https://doi.org/10.1093/mmy/myz092","pdf_url":null,"source":{"id":"https://openalex.org/S93288122","display_name":"Medical Mycology","issn_l":"0268-1218","issn":["0268-1218","1365-280X","1369-3786","1460-2709"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-c","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-70","russia-white-list-1"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Medical Mycology","raw_type":"journal-article"},{"id":"pmid:32476008","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/32476008","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Medical mycology","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.9940000176429749}],"study_designs":[],"awards":[{"id":"https://openalex.org/G3821986886","display_name":null,"funder_award_id":"21702-5014","funder_id":"https://openalex.org/F4320338478","funder_display_name":"U.S. Army Medical Research Acquisition Activity"}],"funders":[{"id":"https://openalex.org/F4320338478","display_name":"U.S. Army Medical Research Acquisition Activity","ror":null}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":25,"referenced_works":["https://openalex.org/W1586299514","https://openalex.org/W2017674647","https://openalex.org/W2057772850","https://openalex.org/W2101438344","https://openalex.org/W2106743979","https://openalex.org/W2108741132","https://openalex.org/W2127982840","https://openalex.org/W2131989241","https://openalex.org/W2139600928","https://openalex.org/W2157308892","https://openalex.org/W2557605278","https://openalex.org/W2559853894","https://openalex.org/W2596131882","https://openalex.org/W2610593277","https://openalex.org/W2625315574","https://openalex.org/W2737245802","https://openalex.org/W2767031614","https://openalex.org/W2769470002","https://openalex.org/W2791611748","https://openalex.org/W2804928496","https://openalex.org/W2810179690","https://openalex.org/W2886093859","https://openalex.org/W2904183644","https://openalex.org/W2905319985","https://openalex.org/W4211106100"],"related_works":["https://openalex.org/W2903246951","https://openalex.org/W2769470002","https://openalex.org/W2905319985","https://openalex.org/W2810179690","https://openalex.org/W2157308892","https://openalex.org/W2791611748","https://openalex.org/W7098189713","https://openalex.org/W1975193480","https://openalex.org/W2171797696","https://openalex.org/W2610593277"],"abstract_inverted_index":{"Aspergillus":[0],"spp.":[1],"infections":[2],"remain":[3],"a":[4,17,32,93,119,181,228],"global":[5],"concern,":[6],"with":[7,92,96,107],"\u223c30%":[8],"attributable":[9],"mortality":[10],"of":[11,59,65,71,84,111,157,231,239,244],"invasive":[12],"aspergillosis":[13],"(IA).":[14],"VT-1598":[15,60,72,123,240],"is":[16],"novel":[18],"fungal":[19,130,208,223],"CYP51":[20,178],"inhibitor":[21],"designed":[22],"for":[23,159,162,176,188,241],"exquisite":[24],"selectivity":[25],"versus":[26],"human":[27],"CYP":[28],"enzymes":[29],"to":[30,173],"achieve":[31],"maximal":[33,38],"therapeutic":[34],"index":[35],"and":[36,56,78,88,113,142,152,168,203,207],"therefore":[37],"antifungal":[39,46],"efficacy.":[40],"Previously,":[41],"its":[42],"broad-spectrum":[43],"in":[44,61,108,118,128,221,227],"vitro":[45,109],"activity":[47],"was":[48,196,216],"reported.":[49],"We":[50],"report":[51],"here":[52],"the":[53,163,192,199,242],"pharmacokinetics":[54],"(PK)":[55],"pharmacodynamics":[57],"(PD)":[58],"neutropenic":[62],"mouse":[63],"models":[64],"IA.":[66,232],"The":[67,154],"plasma":[68],"area-under-the-curve":[69],"(AUC)":[70],"increased":[73],"nearly":[74],"linearly":[75],"between":[76],"5":[77,82],"40":[79,97,149,204],"mg/kg":[80,98,141,150,205],"after":[81,191],"days":[83,190],"QD":[85,133,139,151],"administration":[86],"(155":[87],"1033":[89],"\u03bcg*h/ml,":[90],"respectively),":[91],"further":[94,237],"increase":[95],"BID":[99],"dosing":[100],"(1354":[101],"\u03bcg*h/ml).":[102],"When":[103],"A.":[104],"fumigatus":[105],"isolates":[106],"susceptibilities":[110],"0.25":[112],"1.0":[114],"\u03bcg/ml":[115],"were":[116,166,186,225],"used":[117],"disseminated":[120],"IA":[121],"model,":[122],"treatment":[124,243],"produced":[125],"no":[126],"decrease":[127],"kidney":[129],"burden":[131,209,224],"at":[132,138,148,198],"10":[134],"mg/kg,":[135],"intermediate":[136],"decreases":[137,147],"20":[140],"maximum":[143,146],"or":[144],"near":[145],"BID.":[153],"PK/PD":[155],"relationships":[156],"AUCfree/MIC":[158],"1-log":[160],"killing":[161],"two":[164],"strains":[165],"5.1":[167],"1.6":[169],"h,":[170],"respectively,":[171],"similar":[172],"values":[174],"reported":[175],"approved":[177],"inhibitors.":[179],"In":[180],"survival":[182,195],"study":[183],"where":[184],"animals":[185],"observed":[187,226],"12":[189],"last":[193],"treatment,":[194],"100%":[197],"doses":[200],"tested":[201],"(20":[202],"QD),":[206],"remained":[210],"suppressed":[211],"even":[212],"though":[213],"drug":[214],"wash-out":[215],"complete.":[217],"Similar":[218],"dose-dependent":[219],"reductions":[220],"lung":[222],"pulmonary":[229],"model":[230],"These":[233],"data":[234],"strongly":[235],"support":[236],"exploration":[238],"this":[245],"lethal":[246],"mold":[247],"infection.":[248]},"counts_by_year":[{"year":2026,"cited_by_count":3},{"year":2025,"cited_by_count":7},{"year":2024,"cited_by_count":3},{"year":2022,"cited_by_count":2},{"year":2021,"cited_by_count":4},{"year":2020,"cited_by_count":1}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2020-06-05T00:00:00"}