ArticleAntimicrobial agents and chemotherapy2015
Efficacy of the clinical agent VT-1161 against fluconazole-sensitive and -resistant Candida albicans in a murine model of vaginal candidiasis.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- The Upcoming Antifungal Drugs in Clinical Development for the Treatment of Invasive Candidiasis.Infection and drug resistance · 2026Review
- Next-generation antifungal drugs: Mechanisms, efficacy, and clinical prospects.Acta pharmaceutica Sinica. B · 2025Review
- Dermatophytosis in context of Trichophyton rubrum: host defense mechanisms, virulence factors, and treatment innovations.Molecular biology reports · 2025Review
- Understanding the mechanisms of resistance to azole antifungals inJAC-antimicrobial resistance · 2025Review
- Novel antifungals and treatment approaches to tackle resistance and improve outcomes of invasive fungal disease.Clinical microbiology reviews · 2024Review
- Advancements and challenges in antifungal therapeutic development.Clinical microbiology reviews · 2024Review
- Preclinical Pharmacokinetic/Pharmacodynamic Studies and Clinical Trials in the Drug Development Process of EMA-Approved Antifungal Agents: A Review.Clinical pharmacokinetics · 2024Review
- SelectedMolecules (Basel, Switzerland) · 2023Article
- Anti-International journal of molecular sciences · 2023Article
- New Antifungal Agents with Azole Moieties.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Pharmacodynamics, Mechanisms of Action and Resistance, and Spectrum of Activity of New Antifungal Agents.Journal of fungi (Basel, Switzerland) · 2022Review
- Advances in Antifungal Drug Development: An Up-To-Date Mini Review.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Advances in anti-fungal therapies.Mycopathologia · 2021Review
- Current and promising pharmacotherapeutic options for candidiasis.Expert opinion on pharmacotherapy · 2021Article
- Drug Resistance and Novel Therapeutic Approaches in Invasive Candidiasis.Frontiers in cellular and infection microbiology · 2021Review
- Investigational Agents for the Treatment of Resistant Yeasts and Molds.Current fungal infection reports · 2021Review
- Small-Molecule Inhibitors Targeting Sterol 14α-Demethylase (CYP51): Synthesis, Molecular Modelling and Evaluation Against Candida albicans.ChemMedChem · 2020Article
- Hope on the Horizon: Novel Fungal Treatments in Development.Open forum infectious diseases · 2020Review
- Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungus Candida albicans.The Journal of antimicrobial chemotherapy · 2020Review
- Impact of the Major Candida glabrata Triazole Resistance Determinants on the Activity of the Novel Investigational Tetrazoles VT-1598 and VT-1161.Antimicrobial agents and chemotherapy · 2019Article
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6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC) remain major health problems for women. VT-1161, a novel fungal CYP51 inhibitor which has potent antifungal activity against fluconazole-sensitive Candida albicans, retained its in vitro potency (MIC50 of ≤0.015 and MIC90 of 0.12 μg/ml) against 10 clinical isolates from VVC or RVVC patients resistant to fluconazole (MIC50 of 8 and MIC90 of 64 μg/ml). VT-1161 pharmacokinetics in mice displayed a high volume of distribution (1.4 liters/kg), high oral absorption (73%), and a long half-life (>48 h) and showed rapid penetration into vaginal tissue. In a murine model of vaginal candidiasis using fluconazole-sensitive yeast, oral doses as low as 4 mg/kg VT-1161 significantly reduced the fungal burden 1 and 4 days posttreatment (P < 0.0001). Similar VT-1161 efficacy was measured when an isolate highly resistant to fluconazole (MIC of 64 μg/ml) but fully sensitive in vitro to VT-1161 was used. When an isolate partially sensitive to VT-1161 (MIC of 0.12 μg/ml) and moderately resistant to fluconazole (MIC of 8 μg/ml) was used, VT-1161 remained efficacious, whereas fluconazole was efficacious on day 1 but did not sustain efficacy 4 days posttreatment. Both agents were inactive in treating an infection with an isolate that demonstrated weaker potency (MICs of 2 and 64 μg/ml for VT-1161 and fluconazole, respectively). Finally, the plasma concentrations of free VT-1161 were predictive of efficacy when in excess of the in vitro MIC values. These data support the clinical development of VT-1161 as a potentially more efficacious treatment for VVC and RVVC.
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