fungal CYP51 / lanosterol 14-alpha-demethylase

Class

triazole antifungal (inhaled, investigational for fungal-sensitized/ABPA-associated severe asthma)

Pathway

inhibits ergosterol biosynthesis in fungal cell membranes, causing fungal cell lysis; studied in asthma to reduce airway fungal (e.g. Aspergillus) burden driving inflammation

This target is fungal CYP51, also called lanosterol 14-alpha-demethylase, an enzyme fungi require to build ergosterol, the sterol that gives their cell membranes structural integrity and proper function. Triazole antifungals inhibit this enzyme, halting ergosterol production; the resulting membrane defects impair fungal growth and can cause fungal cell lysis, the breakdown of the cell. Because ergosterol has no equivalent role in human cells (which use cholesterol, made by a different pathway), this enzyme has long been a mainstay target for treating fungal infections ranging from superficial skin disease to invasive systemic infections. A newer application under investigation is delivering a triazole directly to the airways by inhalation, rather than systemically, in people with severe asthma linked to fungal sensitization, including allergic bronchopulmonary aspergillosis (ABPA). In these conditions, persistent fungal colonization of the airways, often by Aspergillus species, is thought to sustain chronic allergic inflammation. By suppressing local fungal burden through CYP51 inhibition, inhaled triazole therapy aims to reduce this inflammatory drive at its source, an approach conceptually distinct from anti-inflammatory asthma medicines that act downstream on the immune response itself.