VT-1129

**VT-1129** (quilseconazole) is an investigational oral small-molecule antifungal agent developed by Viamet Pharmaceuticals (now Mycovia Pharmaceuticals) using Metallophile technology. It acts as a highly potent and selective inhibitor of fungal **CYP51** (lanosterol 14α-demethylase), a metalloenzyme critical for ergosterol biosynthesis in fungal cell membranes, demonstrating tight binding (Kd 14-25 nM) to Cryptococcus species CYP51 comparable to azoles like fluconazole but with weak affinity for human CYP51 (Kd 4.53 μM) and minimal inhibition of human CYPs (e.g., CYP2C9, CYP2C19, CYP3A4), reducing drug-drug interaction risk. Primarily indicated for **cryptococcal meningitis** caused by *Cryptococcus neoformans* and *C. gattii*, it shows superior in vitro potency (GM MIC 0.027-0.205 μg/ml) over fluconazole, even against azole-resistant isolates, high CNS penetration (brain/plasma ratio ~1.5), prolonged half-life (>6 days in mice), and robust efficacy in murine models via loading dose-maintenance regimens, with FDA **orphan drug**, **Fast Track**, and **QIDP** designations.[1][2][3][4][11][12]

Brand names

Quilseconazole