title: Fungal CYP51 Inhibitors VT-1161 and VT-1129 Exhibit StrongIn VitroActivity against Candida glabrata and C. krusei Isolates Clinically Resistant to Azole and Echinocandin Antifungal Compounds.
abstract: Thein vitroactivities of fungal CYP51 inhibitors VT-1161 and VT-1129 were determined forCandida glabrata(n= 34) andC. krusei(n= 50).C. glabrataisolates were screened for FKS gene mutations. All isolates were resistant clinically and/orin vitroto at least one standard antifungal compound. VT-1161 and VT-1129 MICs for all isolates were at least 5-fold below achievable human plasma levels for VT-1161. VT-1161 and VT-1129 are promising for the treatment of resistantC. glabrataandC. kruseiinfections.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: W A
authors.initials: WA
authors.lastname: Schell
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Jones
authors.affiliation: Viamet Pharmaceuticals, Inc., Durham, North Carolina, USA.
authors.forename: E P
authors.initials: EP
authors.lastname: Garvey
authors.affiliation: Viamet Pharmaceuticals, Inc., Durham, North Carolina, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Hoekstra
authors.affiliation: Viamet Pharmaceuticals, Inc., Durham, North Carolina, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Schotzinger
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA Barbara.alexander@dm.duke.edu.
authors.forename: B D
authors.initials: BD
authors.lastname: Alexander
mesh_terms: D058888:14-alpha Demethylase Inhibitors / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology; D002175:Candida / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification; D041221:Candida glabrata / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D025141:Drug Resistance, Fungal / Q000187:drug effects*; D054714:Echinocandins / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005964:Glucosyltransferases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011725:Pyridines / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D058888:14-alpha Demethylase Inhibitors; D000935:Antifungal Agents; D001393:Azoles; D054714:Echinocandins; D005656:Fungal Proteins; D011725:Pyridines; D013777:Tetrazoles; C000612857:VT-1129; C000599187:VT-1161; D005964:Glucosyltransferases
keywords: Candida glabrata; Candida krusei; antifungal susceptibility testing; resistance