Update on antifungals targeted to the cell wall: focus on beta-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).
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DuPont Pharmaceuticals, Experimental Station, E400/3456A, P.O. Box 80400, Wilmington, DE 19880-0400, USA. nafsikag@aol.com
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D000077336:Caspofungin; D002473:Cell Wall / Q000187:drug effects; D002687:Chitin Synthase / Q000037:antagonists & inhibitors; D054714:Echinocandins; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005936:Glucans / Q000096:biosynthesis*; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors*; D055666:Lipopeptides; D008074:Lipoproteins / Q000494:pharmacology; D000077551:Micafungin; D010455:Peptides; D010456:Peptides, Cyclic / Q000494:pharmacology; D047071:beta-Glucans
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D054714:Echinocandins; D004791:Enzyme Inhibitors; D005936:Glucans; D055666:Lipopeptides; D008074:Lipoproteins; D010455:Peptides; D010456:Peptides, Cyclic; D047071:beta-Glucans; C033363:beta-1,3-glucan; D005964:Glucosyltransferases; C040232:glucan synthase; D002687:Chitin Synthase; D000077336:Caspofungin; D000077551:Micafungin