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  • Review Article
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The antifungal pipeline: a reality check

Nature Reviews Drug Discovery volume 16, pages 603–616 (2017)Cite this article

Subjects

Key Points

  • Invasive fungal infections are a substantial medical concern, particularly in immunocompromised patients. As medical advances increase the size of this population, invasive fungal infections will continue to be a large medical issue.

  • Progress has been made recently in developing antifungal agents, but more agents, particularly those with a broad spectrum and low toxicity, are needed. New formulations of existing antifungals are being developed to address these issues.

  • Novel antifungal pathways and targets are being used to identify potential antifungal agents with new mechanisms of action, which could lead to the development of new drugs.

  • Alternative strategies to target drugs to infection sites, to repurpose agents for antifungal use and to use the immune system as adjunctive therapies are discussed in this Review.

Abstract

Invasive fungal infections continue to appear in record numbers as the immunocompromised population of the world increases, owing partially to the increased number of individuals who are infected with HIV and partially to the successful treatment of serious underlying diseases. The effectiveness of current antifungal therapies — polyenes, flucytosine, azoles and echinocandins (as monotherapies or in combinations for prophylaxis, or as empiric, pre-emptive or specific therapies) — in the management of these infections has plateaued. Although these drugs are clinically useful, they have several limitations, such as off-target toxicity, and drug-resistant fungi are now emerging. New antifungals are therefore needed. In this Review, I discuss the robust and dynamic antifungal pipeline, including results from preclinical academic efforts through to pharmaceutical industry products, and describe the targets, strategies, compounds and potential outcomes.

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Figure 1: Currently available antifungal compounds and future derivatives thereof.
Figure 2: Antifungal targets.

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Acknowledgements

The author has research support from Public Health Service Grants (AI73896, AI04533, AI93257).

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    John R. Perfect

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The author declares research grants, consulting arrangements, honorariums and advisory committees from the following companies: Merck & Co., Astellas, Pfizer Inc, F2G, Vical, Arno Therapeutics, Cidara, Scynexis, Viamet, Matinas BioPharma, Amplyx Pharmaceuticals and Teva Pharmaceutical Industries.

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Perfect, J. The antifungal pipeline: a reality check. Nat Rev Drug Discov 16, 603–616 (2017). https://doi.org/10.1038/nrd.2017.46

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