VT-1598 (C09-1184-651)

VT-1598 is an orally active and selective fungal inhibitor targeting CYP51. VT-1598 shows anti-fungal activity against Candida auris.In VitroVT-1598 (0.015-8 μg/mL; 24 h) demonstrates in vitro activity against C. auris. VT-1598 (0.03125-0.125 μg/mL; 24 h) shows highly effects in inhibiting the in vitro growth of clinical Candida isolates. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: 100 C. auris isolates Concentration: 0.015-8 μg/mL Incubation Time: 24 hours Result: Showed MICs ranging from 0.03 to 8 μg/ mL against all isolates, with MIC 50 and MIC 90 values of 0.25 and 1 μg/mL, respectively. Cell Viability AssayCell Line: 28 Candida isolates obtained from mucosal sites of APECED patients Concentration: 0.03125-0.125 μg/mL Incubation Time: 24 hours Result: Demonstrated potent in vitro activity against all 28 isolates (MIC range=0.03125-0.125 mg/L), with the MIC 50 and MIC 90 values of 0.0625 and 0.125 mg/L, respectively.In VivoVT-1598 (oral gavage; 5, 15, and 50 mg/kg; once daily; 7 d) treatment shows a significant and dose-dependent survival advantage, and dose-dependent reductions in fungal burden . VT-1598 (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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Mice model of invasive candidiasis Dosage: 5, 15, 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 log 10 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. albicansDosage: 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.Form:Solid. Specification: 0.99 Molecular Formula: C31H20F4N6O2 Molecular Weight: 584.52 PubChem CID: 126715974 Isomeric SMILES: C1=CC(=CC=C1COC2=CC=C(C=C2)C#CC3=CN=C(C=C3)C([C@](CN4C=NN=N4)(C5=C(C=C(C=C5)F)F)O)(F)F)C#N