VT-1161

VT-1161 is an antifungal agent. It selectively binds to C. albicans lanosterol 14-alpha-demethylase (Kd = 39 nM), also known as cytochrome P450 (CYP) isoform CYP51, over human lanosterol 14-alpha-demethylase at 86 µM and does not inhibit human CYP2C9, CYP2C19, or CYP3A4 (IC50s = 99, 72, and 65 µM, respectively). VT-1161 (0. µg/ml) decreases ergosterol levels and induces the accumulation of lanosterol, eburicol, 14alpha-methylfecosterol, and 14alpha-methylergosta-8,24(28)-dien-3beta,6alpha-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. It also binds to T. cruzi lanosterol 14-alpha-demethylase (Kd = 24 nM), is active against T. cruzi in vitro (EC50 = 2. nM), and reduces parasitemia in T. cruzi-infected mice when administered at a dose of 50 mg/kg. Formulations containing VT-1161 have been used in the prevention of recurrent vulvovaginal candidiasis (RVVC). InChI: InChI=1S/C23H16F7N5O2/c24-16-4-7-18(19(25)9-16)21(36,11-35-13-32-33-34-35)23(29,30)20-8-3-15(10-31-20)14-1-5-17(6-2-14)37-12-22(26,27)28/h1-10,13,36H,11-12H2/t21-/m0/s1 InChIKey: IDUYJRXRDSPPRC-NRFANRHFSA-N SMILES: FC(F)(COC1=CC=C(C2=CC=C(C(F)([C@@](C3=C(C=C(C=C3)F)F)(CN4N=NN=C4)O)F)N=C2)C=C1)F