Update on antifungals targeted to the cell wall: focus on β-1,3-glucan synthase inhibitors

Currently available antifungal drugs for serious infections are either fungistatic and vulnerable to resistance (azoles) or fungicidal but toxic to the host (polyenes). Cell wall-acting antifungals are inherently selective and fungicidal, features that make them particularly attractive for clinical development. Three classes of such compounds, targeted respectively to chitin synthase (nikkomycins), beta-1,3-glucan synthase (echinocandins) and mannoproteins (pradimicins/benanomicins), have entered clinical development. While nikkomycins and pradimicins/benanomicins are no longer in development, echinocandins have emerged as potentially clinically useful and three compounds, caspofungin (MK-991, L-743,872), micafungin (FK-463) and anidulafungin (LY-303366) are in late clinical development (Phase II and III).