Fosmanogepix

Fosmanogepix

Clinical data
Other names	APX001, APX-001
ATC code	None
Legal status
Legal status	Investigational
Identifiers
IUPAC name [2-Amino-3-(3-{4-[(2-pyridinyloxy)methyl]benzyl}-1,2-oxazol-5-yl)-1-pyridiniumyl]methyl hydrogen phosphate
CAS Number	2091769-17-2
PubChem CID	44123754
DrugBank	15183
ChemSpider	64853722
UNII	1XQ871489P
KEGG	D11694
Chemical and physical data
Formula	C22H21N4O6P
Molar mass	468.406 g·mol−1
3D model (JSmol)	Interactive image
SMILES c1ccnc(c1)OCc2ccc(cc2)Cc3cc(on3)c4ccc[n+](c4N)COP(=O)(O)[O-]
InChI InChI=1S/C22H21N4O6P/c23-22-19(4-3-11-26(22)15-31-33(27,28)29)20-13-18(25-32-20)12-16-6-8-17(9-7-16)14-30-21-5-1-2-10-24-21/h1-11,13,23H,12,14-15H2,(H2,27,28,29) Key:JQONJQKKVAHONF-UHFFFAOYSA-N

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

1. "What we do : Basilea".
2. Hoenigl M, Sprute R, Egger M, Arastehfar A, Cornely OA, Krause R, et al. (October 2021). "The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin". Drugs. 81 (15): 1703–1729. doi:10.1007/s40265-021-01611-0. PMC   8501344 . PMID   34626339.
3. "Fosmanogepix - Amplyx Pharmaceuticals". AdisInsight. Springer Nature Switzerland AG. Retrieved June 27, 2022.
4. Badali H, Patterson HP, Sanders CJ, Mermella B, Gibas CF, Ibrahim AS, et al. (May 2021). "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). doi:10.1128/AAC.02343-20. PMC   8315997 . PMID   33722886.
5. "GWT1". Saccharomyces Genome Database. Stanford University. Retrieved 2022-06-28.
6. Shaw KJ, Ibrahim AS (October 2020). "Fosmanogepix: A Review of the First-in-Class Broad Spectrum Agent for the Treatment of Invasive Fungal Infections". Journal of Fungi. 6 (4): 239. doi: 10.3390/jof6040239 . PMC   7711534 . PMID   33105672.
7. Pfaller MA, Huband MD, Flamm RK, Bien PA, Castanheira M (September 2021). "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. doi: 10.1016/j.jgar.2021.04.012 . PMID   34051400.
8. Strong N, Meeks G, Sheth SA, McCullough L, Villalba JA, Tan C, et al. (February 2024). "Neurovascular Complications of Iatrogenic Fusarium solani Meningitis". The New England Journal of Medicine. 390 (6): 522–529. doi:10.1056/NEJMoa2308192. PMC   11905984 . PMID   38324485. S2CID   267547035.