VT-1161

VT-1161 is an antifungal agent.^1,2 It selectively binds to C. albicans lanosterol 14-α-demethylase (K_d = 39 nM), also known as cytochrome P450 (CYP) isoform CYP51, over human lanosterol 14-α-demethylase at 86 µM and does not inhibit human CYP2C9, CYP2C19, or CYP3A4 (IC₅₀s = 99, 72, and 65 µM, respectively).¹ VT-1161 (0.004 µg/ml) decreases ergosterol levels and induces the accumulation of lanosterol, eburicol, 14α-methylfecosterol, and 14α-methylergosta-8,24(28)-dien-3β,6α-diol in C. albicans. In vivo, VT-1161 (25 mg/kg) decreases vaginal lavage fluid levels of C. albicans in mouse models of fluconazole-sensitive and -resistant candidiasis.² It also binds to T. cruzi lanosterol 14-α-demethylase (K_d = 24 nM), is active against T. cruzi in vitro (EC₅₀ = 2.5 nM), and reduces parasitemia in T. cruzi-infected mice when administered at a dose of 50 mg/kg.³ Formulations containing VT-1161 have been used in the prevention of recurrent vulvovaginal candidiasis (RVVC).

WARNING This product is not for human or veterinary use.

1. Warrilow, A.G., Hull, C.M., Parker, J.E., et al. The clinical candidate VT-1161 is a highly potent inhibitor of Candida albicans CYP51 but fails to bind the human enzyme. Antimicrob. Agents Chemother. 58(12), 7121-7127 (2014).

2. Garvey, E.P., Hoekstra, W.J., Schotzinger, R.J., et al. Efficacy of the clinical agent VT-1161 against fluconazole-sensitive and -resistant Candida albicans in a murine model of vaginal candidiasis. Antimicrob. Agents Chemother. 59(9), 5567-5573 (2015).

3. Hoekstra, W.J., Hargrove, T.Y., Wawrzak, Z., et al. Clinical candidate VT-1161’s antiparasitic effect in vitro, activity in a murine model of Chagas disease, and structural characterization in complex with the target enzyme CYP51 from Trypanosoma cruzi. Antimicrob. Agents Chemother. 60(2), 1058-1066 (2015).