| Hazard Information | Back Directory | [Uses]
VT-1598 tosylate is an orally active and selective fungal inhibitor targeting CYP51. VT-1598 tosylate shows anti-fungal activity against C. auris[1][2]. VT-1598 (tosylate) is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups. | [in vivo]
VT-1598 tosylate (oral gavage; 5, 15, and 50?mg/kg; once daily; 7 d) shows a significant and dose-dependent survival advantage for mice, and dose-dependent reductions in fungal burden in mice[1].
VT-1598 tosylate (oral gavage; 3.2, 8, and 20?mg/kg; once daily; 4 d) is present to a great extent in the plasma and tongue after oral administration in Act1-deficient mice infected with C. albicans[2]. | Animal Model: | Mice model of invasive candidiasis[1] | | Dosage: | 5 mg/kg, 15 mg/kg, and 50?mg/kg | | Administration: | Oral gavage; once daily; 7 days | | Result: | Observed median survival in the VT-1598 15 mg/kg and 50 mg/kg groups (15?days and >21?days, respectively) longer than the control group.
Observed kidney fungal burden in mice treated with 15 mg/kg and 50 mg/kg doses (mean log10 CFU/g, 5.40 and 3.67, respectively) lower than the vehicle control group.
Showed mean trough concentrations 1.55?μg/mL after 7?days of therapy in the 5 mg/kg group, 6.78?μg/mL in the 15 mg/kg group, and 14.2?μg/mL in the 50 mg/kg group. |
| Animal Model: | Act1-deficient mice infected with C. albicans[2] | | Dosage: | 3.2, 8, and 20?mg/kg | | Administration: | Oral gavage; once daily; 4 days | | Result: | Resulted in high concentrations in the plasma and tongues of Candida-infected mice. |
| [References]
[1] Nathan P Wiederhold, et al. The Fungal Cyp51-Specific Inhibitor VT-1598 Demonstrates In Vitro and In Vivo Activity against Candida auris. Antimicrob Agents Chemother. 2019 Feb 26;63(3):e02233-18. DOI:10.1128/AAC.02233-18
[2] Timothy J Break, et al. VT-1598 inhibits the in vitro growth of mucosal Candida strains and protects against fluconazole-susceptible and -resistant oral candidiasis in IL-17 signalling-deficient mice. J Antimicrob Chemother. 2018 Aug 1;73(8):2089-2094. DOI:10.1093/jac/dky170 |
|
|