VT-1598 tosylate

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].

Research Areas >> Infection

CYP51[1]

VT-1598 甲苯磺酸盐 (0.015-8 μg/mL; 24 h) 对临床念珠菌 (C. auris) 具有体外抑制活性[1]。 VT-1598 甲苯磺酸盐 (0.03125-0.125 μg/mL; 24 h) 对临床念珠菌 (C. auris) 的体外生长有显著抑制作用[2]。

VT-1598 甲苯磺酸盐 (口服灌胃; 5, 15, and 50 mg/kg; 每天一次; 7 天) 处理小鼠，使其呈剂量依赖性的生存优势，VT-1598 还剂量依赖性降低小鼠体内的真菌负荷量[1]。 VT-1598 甲苯磺酸盐 (口服灌胃; 3.2, 8, and 20 mg/kg; 每天一次; 4 天) 在感染白色念珠菌 (C. albicans) 的 Act1 缺陷小鼠的血浆和舌中大量存在[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.

[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.  

[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.