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Fosmanogepix

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Fosmanogepix
Clinical data
Other namesAPX001, APX-001
ATC code
  • None
Legal status
Legal status
  • Investigational
Identifiers
  • [2-Amino-3-(3-{4-[(2-pyridinyloxy)methyl]benzyl}-1,2-oxazol-5-yl)-1-pyridiniumyl]methyl hydrogen phosphate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
Chemical and physical data
FormulaC22H21N4O6P
Molar mass468.406 g·mol−1
3D model (JSmol)
  • c1ccnc(c1)OCc2ccc(cc2)Cc3cc(on3)c4ccc[n+](c4N)COP(=O)(O)[O-]
  • 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 (later acquired by Pfizer.[1]) It is being investigated for its potential to treat various fungal infections including aspergillosis, candidaemia, and coccidioidomycosis.[2]

Fosmanogepix is a prodrug and is converted into the active drug form, manogepix, after administration.[3] Manogepix targets the inositol acyltransferase Gwt1 (Glycosylphosphatidylinositol-anchored Wall protein Transfer 1[4]), an enzyme in the glycosylphosphatidylinositol (GPI) anchor biosynthesis pathway.[5] Inhibiting this enzyme prevents the fungi from producing certain proteins essential to its life cycle.[clarification needed] This mechanism of action is novel; therefore, if approved, fosmanogepix would become a first-in-class medication.[5][6]

References

  1. ^ 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.
  2. ^ "Fosmanogepix - Amplyx Pharmaceuticals". Adis Insight. Retrieved June 27, 2022.
  3. ^ 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.
  4. ^ "GWT1". Saccharomyces Genome Database. Stanford University. Retrieved 2022-06-28.
  5. ^ a b 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.
  6. ^ 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.


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