Authors: Martha Powell, Future Science Group
Researchers from the University of Liverpool (UK) and F2G Limited (Eccles, UK) have developed a novel antifungal compound, F901318, that could help in treating invasive fungal infections such as aspergillosis.
Currently, there are relatively few agents licensed for use against fungal infections, in addition, emerging antifungal resistance and drug toxicity can make treatment very challenging. F901318 represents the lead compound of a novel antifungal class termed ‘orotomides’ – the first new class of antifungals to be discovered in the last three decades. F901318 has a novel mechanism of action, inhibiting the fungal enzyme dihydroorotate dehydrogenase and has previously demonstrated potent activity against Aspergillus species.
Understanding the relationship between drug doses, the concentration of drug in the body and antifungal effect is critical to progressing compounds for clinical use. The team, led by William Hope (University of Liverpool), therefore aimed to characterize the pharmacodynamics of this drug.
F901318 was tested for end-point parameters including serum galactomannan, survival and histopathology in mouse and rabbit models, in addition, it was benchmarked against a clinically relevant treatment. The researchers discovered that F901318 exhibits time-dependent antifungal activity and established pharmacodynamics targets such as the minimum inhibitory concentration. The team hope that these findings can now be used to select optimal drug regimens for Phase II and III clinical trials
Hope concluded: “Antifungal resistance represents a major global clinical challenge. This study provides the necessary information to enable F901318 to be developed for clinical use.”
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Sources: Hope WW, McEntree L, Lovermore J et al. Pharmacodynamics of the Orotomides against Aspergillus fumigatus: New Opportunities for Treatment of Multidrug-Resistant Fungal Disease. mBio. 8(4) e01157–17. www.eurekalert.org/pub_releases/2017-10/uol-rhd100617.php