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. Author manuscript; available in PMC: 2023 May 24.
Published in final edited form as: Trends Pharmacol Sci. 2023 Mar 1;44(3):162–174. doi: 10.1016/j.tips.2022.12.002

Figure 1. Mechanism of action of antifungal agents.

Figure 1

Azoles (inhibit ergosterol synthesis), echinocandins (inhibit β-1,3 glucan synthesis), and polyenes (generate membrane pores) are the most commonly used antifungals in the treatment of serious fungal infections, all of which target the cell periphery to disrupt cellular integrity. The antimetabolite 5-flucytosine (5FC), which is most often used in combination with amphotericin B in the treatment of candidemia or cryptococcosis, inhibits RNA synthesis. Several promising antifungals are under development and in clinical trials. Ibrexafungerp inhibits β-1,3 glucan synthesis (like caspofungin) through interaction with the catalytic FKS1 subunit of β-1,3 glucan synthase. Olorofim is a first-in-class orotomide that dysregulates DNA (pyrimidine) synthesis through inhibition of dihydroorotate dehydrogenase. Manogepix (the active derivative of the prodrug fosmanogepix) disrupts glycosylphosphatidylinositol (GPI) anchoring at the cell periphery via inhibition of Gwt1. Novamycin (NP339) partitions into the plasma membrane and results in the formation of membrane pores. Image created using BioRender.