Rezafungin Acetate (syn: biafungin acetate) is the acetate salt of Rezafungin, a semi-synthetic, next-generation, broad-spectrum echinocandin. It is antifungal agent with activity against Aspergillus, Candida, and Pneumocystis spp. It is a β-glucan synthase inhibitor and structural analog of anidulafungin. It is synthesized from anidulafungin, a fermentation product of the fungus Aspergillus nidulans. It is then chemically modified to render Rezafungin. Rezafungin is a cyclic hexapeptide with its lipophilic tail derived from anidulafungin, with a choline moiety at the C5 ornithine position resulting in increased in vitro and in vivo stability compared with other echinocandins. The acetate salt is obtained by combining Rezafungin with one molar equivalent of acetic acid.
Rezafungin Acetate is freely soluble in DMSO.
| Mechanism of Action |
Rezafungin acts via inhibition of the 1,3-β-d-glucan synthase enzyme complex. The major cell wall component 1,3-β-d-glucan is present in many pathogenic fungi thus when it's not synthesized, this leads to osmotic instability and fungal cell lysis. |
| Spectrum |
Broad-spectrum antifungal activity against Aspergillus, Candida and Pneumocystis species. It lacks activity against fungi that are intrinsically resistant to the echinocandin class like Cryptococcus, Rhodotorula, and Trichosporon species. Basidiomycetes, Mucorales, Fusarium spp., and Ajellomycetaceae are intrinsically resistant to Rezafungin. |
| Molecular Formula | C65H88N8O19 |
| Microbiology Applications |
Rezafungin has similar susceptibility and resistance to other echinocandins, and its potency was comparable with other echinocandins (Sofjan et al, 2018). In vitro studies suggest minimal interaction with recombinant cytochrome P450 enzymes. Similarly to anidulafungin, Rezafungin binds to human, mouse, rat, and primate plasma proteins (Ong et al, 2016). Rezafungin has similarities with older echinocandins and they behave similarly in vitro with regard to MIC50, IC50, spectrum, target, and resistance mechanisms (Garcia Effron, 2020). |
| Eukaryotic Cell Culture Applications |
Metabolic stability studies found no evidence of biotransformation as Rezafungin was stable in liver microsomes (rat, monkey and human) and hepatocytes (rat, monkey, dog and human) (Ong et al, 2016). When Rezafungin was incubated with glutathione, there were no reactive intermediates formed. This in contrast to anidulafungin, which forms reactive electrophilic species that can covalently bind to nucleophilic sulfhydral groups. Similarly, caspofungin undergoes spontaneous chemical degradation and generates two potentially reactive intermediates. In contrast, Anidulafungin undergoes a nonenzymatic chemical degradation to a ring-opened product at neutral to basic pH conditions. The design of Rezafungin provides stabilization of the attached choline, preventing subsequent opening of the ring (Ong et al, 2016). |
| References |
Garcia-Effron G (2020) Rezafungin-Mechanisms of action, susceptibility and resistance: Similarities and differences with the other echinocandins. J. Fungi (Basel). 6(4):262 PMID 33139650 Logan A, Wolfe A, Williamson JC (2022) Antifungal resistance and the role of new therapeutic agents. Curr. Infect. Dis .Rep. 2022;24(9):105-116 PMID 35812838 Ong V et al (2016) Preclinical evaluation of the stability, safety, and efficacy of CD101, a novel echinocandin. Antimicrob. Agents Chemother. 60 (11):00701-16 Sofjan AK et al (2018) Rezafungin (CD101), a next-generation echinocandin: A systematic literature review and assessment of possible place in therapy. J. Glob. Antimicrob. Resist. 14:58-64 PMID 29486356 Wiederhold NP (2022) Pharmacodynamics, mechanisms of action and resistance, and spectrum of activity of new antifungal agents. J. Fungi (Basel) 8(8):857 PMID 36012845 |
