An insight into the antifungal pipeline: selected new molecules and beyond

• Published in: Nature reviews. Drug discovery Vol. 9; no. 9; pp. 719 - 727
• Main Authors: Ostrosky-Zeichner, Luis, Casadevall, Arturo, Galgiani, John N, Odds, Frank C, Rex, John H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2010; Nature Publishing Group
• Subjects: 631/154; 631/1647/338/22/1292; 631/92/609; 692/699/255/1672; Animals; Antifungal agents; Antifungal Agents - pharmacology; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cancer Research; Candidiasis; Dosage and administration; Drug Delivery Systems; Drug Design; Drug therapy; Fungal Vaccines - immunology; Humans; Immunotherapy - methods; Medicinal Chemistry; Molecular Medicine; Mycoses - diagnosis; Mycoses - drug therapy; Mycoses - immunology; Pharmacology/Toxicology; Product development; review-article; United States
• ISSN: 1474-1776; 1474-1784
• DOI: 10.1038/nrd3074

Key Points Invasive fungal infections are increasing in incidence and are associated with considerable mortality. Antifungal research and development is challenging. Other than the fungal cell wall, fungi are metabolically similar to mammalian cells and thus offer few pathogen-specific targets. Clinical development is hampered by challenges in timely and definitive diagnosis of the less common or more resistant fungi. Few new agents in the existing antifungal classes (polyenes, azoles and echinocandins) are being developed. New agents in novel classes such as the sordarins and nikkomycin Z have also been slow in development. Substantial advances have been made in the area of immunotherapy, such as the development of monoclonal antibodies against various fungi, and vaccines against major pathogens such as Candida albicans and Coccidioides spp. The progression of therapeutic agents with pathogen-specific mechanisms of action is of the highest priority in antifungal drug discovery. The incidence of invasive fungal infections is increasing, and there is an unmet need for new antifungal drugs. This article provides an overview of the history of antifungal drug discovery, discusses the current pipeline and presents new vaccination and immunotherapeutic approaches to treat fungal infections. Invasive fungal infections are increasing in incidence and are associated with substantial mortality. Improved diagnostics and the availability of new antifungals have revolutionized the field of medical mycology in the past decades. This Review focuses on recent developments in the antifungal pipeline, concentrating on promising candidates such as new azoles, polyenes and echinocandins, as well as agents such as nikkomycin Z and the sordarins. Developments in vaccines and antibody-based immunotherapy are also discussed. Few therapeutic products are currently in active development, and progression of therapeutic agents with fungus-specific mechanisms of action is of key importance.