Calcineurin Inhibitors Synergize with Manogepix to Kill Diverse Human Fungal Pathogens.

ABSTRACT: Invasive fungal infections have mortality rates of 30-90%, depending on patient co-morbidities and the causative pathogen. The frequent emergence of drug resistance reduces the efficacy of currently approved treatment options, highlighting an urgent need for antifungals with new modes of action. Addressing this need, fosmanogepix (N-phosphonooxymethylene prodrug of manogepix; MGX) is the first in a new class of gepix drugs, and acts as a broad-spectrum, orally bioavailable inhibitor of the essential fungal glycosylphosphatidylinositol (GPI) acyltransferase Gwt1. MGX inhibits the growth of diverse fungal pathogens and causes accumulation of immature GPI-anchored proteins in the fungal endoplasmic reticulum. Relevant to the ongoing clinical development of fosmanogepix, we report a syn

SUBMITTER: Liston SD 

PROVIDER: S-EPMC9605145 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature