Novel antifungal agents in clinical trials

Abstract

Invasive fungal diseases due to resistant yeasts and molds are an important and increasing public health threat, likely due to a growing population of immunosuppressed hosts, increases in antifungal resistance, and improvements in laboratory diagnostics. The significant morbidity and mortality associated with these pathogens bespeaks the urgent need for novel safe and effective therapeutics. This review highlights promising investigational antifungal agents in clinical phases of development: fosmanogepix, ibrexafungerp, rezafungin, encochleated amphotericin B, oteseconazole (VT-1161), VT-1598, PC945, and olorofim. We examine three first-in-class members of three novel antifungal classes, as well as new agents within existing antifungal classes with improved safety and tolerability profiles due to enhanced pharmacokinetic and pharmacodynamic properties.

Synthesis of Benzimidazole-1,2,4-triazole Derivatives as Potential Antifungal Agents Targeting 14α-Demethylase

“…), antimetabolites (5-fluorocytosine), and echinocandins. − However, the current therapeutic medications face significant obstacles, such as drug toxicity, drug–drug interactions, and drug resistance. That is why it is critical to synthesize effective and safe novel antifungal medications that are both. , …”

“…That is why it is critical to synthesize effective and safe novel antifungal medications that are both. 8,9 Ergosterol is structurally distinct from the sterols found in mammals and plants, and it serves a vital function in modulating the permeability and fluidity of fungal cell membranes. 10 The cytochrome P450 enzyme lanosterol 14α-demethylase (CYP51) is a prominent target for the treatment of fungal infection.…”

“…That is why it is critical to synthesize effective and safe novel antifungal medications that are both. 8 , 9 …”

Activities of Manogepix and Comparators against 1,435 Recent Fungal Isolates Collected during an International Surveillance Program (2020)

“…Accordingly, new antifungal therapies that act through novel mechanisms of action are needed to control the high mortality of IFIs and combat the emergence of resistance to existing treatment regimens. Several antifungal agents with the potential to address the emergence of multidrug-resistant yeasts and molds (i.e., resistant to at least 2 different classes of antifungal agents) are presently in clinical development ( 7 – 13 ).…”

Chitin Biosynthesis in Aspergillus Species

“…Despite these promising properties, to date, there are no studies testing PLE on Aspergillus species. Fortunately, several antifungal compounds, including some with novel antifungal mechanisms, are currently in phases II and III of clinical trials with promise to be commercially available soon [ 178 ]. These compounds do not target chitin biosynthesis and will therefore not be reviewed here.…”