Molecules that Matter – Rezafungin
Rezafungin is an echinocandin with a chemical modification that confers high stability, a longer half-life, and allows for a once-a-week dosing regimen. In March 2023, Cidara, one of our past clients received the fantastic news that rezafungin was approved to treat a group of severe fungal infections commonly faced by hospitalised patients.
The quaternary ammonium side chain in rezafungin prevents the spontaneous degradation to a ring-opened peptide observed in previously approved anti-fungals in this class. Metabolism is instead diverted to the end of the terphenyl, pentyl side chain to form 3 hydroxylated metabolites. O-dealkylation also occurs to a lesser extent to a des-pentyl metabolite.
Hypha were able to make all these metabolites by biotransformation using one of our fungal strains, including their purification and characterisation by NMR spectroscopy.
Reference
Ong V, Wills S, Watson D, Sandison T, Flanagan S. Metabolism, Excretion, and Mass Balance of [14C]-Rezafungin in Animals and Humans. Antimicrob Agents Chemother. 2022 Jan 18;66(1):e0139021. doi: 10.1128/AAC.01390-21. Epub 2021 Oct 18. PMID: 34662192; PMCID: PMC8765310.
