Chemistry:Fosmanogepix
Fosmanogepix is an experimental antifungal drug being developed by Amplyx Pharmaceuticals (now currently by Pfizer and Basilea[1][2]) It is being investigated for its potential to treat various fungal infections including aspergillosis, candidaemia, and coccidioidomycosis.[3]
Fosmanogepix is a prodrug and is converted into the active drug form, manogepix in vivo.[4] Manogepix targets the enzyme GWT1 (Glycosylphosphatidylinositol-anchored Wall protein Transfer 1[5]), an enzyme in the glycosylphosphatidylinositol biosynthesis pathway.[6] Inhibiting this enzyme prevents the fungi from properly modifying certain (so called GPI-anchored) proteins essential to the fungal life cycle. This mechanism of action is totally novel; therefore, if approved, fosmanogepix would become a first-in-class medication.[6][7]
In 2023, the drug was given a compassionate use authorization for four patients with Fusarium solani meningitis.[8]
References
- ↑ "What we do : Basilea". https://www.basilea.com/what-we-do.
- ↑ "The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin". Drugs 81 (15): 1703–1729. October 2021. doi:10.1007/s40265-021-01611-0. PMID 34626339.
- ↑ "Fosmanogepix - Amplyx Pharmaceuticals". AdisInsight. Springer Nature Switzerland AG. https://adisinsight.springer.com/drugs/800043868.
- ↑ "Manogepix, the Active Moiety of the Investigational Agent Fosmanogepix, Demonstrates In Vitro Activity against Members of the Fusarium oxysporum and Fusarium solani Species Complexes". Antimicrobial Agents and Chemotherapy 65 (6). May 2021. doi:10.1128/AAC.02343-20. PMID 33722886.
- ↑ "GWT1". Stanford University. https://www.yeastgenome.org/locus/S000003627.
- ↑ 6.0 6.1 "Fosmanogepix: A Review of the First-in-Class Broad Spectrum Agent for the Treatment of Invasive Fungal Infections". Journal of Fungi 6 (4): 239. October 2020. doi:10.3390/jof6040239. PMID 33105672.
- ↑ "Antimicrobial activity of manogepix, a first-in-class antifungal, and comparator agents tested against contemporary invasive fungal isolates from an international surveillance programme (2018-2019)". Journal of Global Antimicrobial Resistance 26: 117–127. September 2021. doi:10.1016/j.jgar.2021.04.012. PMID 34051400.
- ↑ "Neurovascular Complications of Iatrogenic Fusarium solani Meningitis". The New England Journal of Medicine 390 (6): 522–529. February 2024. doi:10.1056/NEJMoa2308192. PMID 38324485.
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