Fosmanogepix Explained

Atc Prefix:None
Legal Status:Investigational
Cas Number:2091769-17-2
Pubchem:44123754
Unii:1XQ871489P
Chemspiderid:64853722
Drugbank:15183
Kegg:D11694
Synonyms:APX001, APX-001
Iupac Name:[2-Amino-3-(3-{4-[(2-pyridinyloxy)methyl]benzyl}-1,2-oxazol-5-yl)-1-pyridiniumyl]methyl hydrogen phosphate
C:22
H:21
N:4
O:6
P:1
Smiles:c1ccnc(c1)OCc2ccc(cc2)Cc3cc(on3)c4ccc[n+](c4N)COP(=O)(O)[O-]
Stdinchi: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)
Stdinchikey: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]

Notes and References

  1. Web site: What we do : Basilea .
  2. Hoenigl M, Sprute R, Egger M, Arastehfar A, Cornely OA, Krause R, Lass-Flörl C, Prattes J, Spec A, Thompson GR, Wiederhold N, Jenks JD . The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin . Drugs . 81 . 15 . 1703–1729 . October 2021 . 34626339 . 8501344 . 10.1007/s40265-021-01611-0 .
  3. Web site: Fosmanogepix - Amplyx Pharmaceuticals . AdisInsight . Springer Nature Switzerland AG . June 27, 2022 .
  4. Badali H, Patterson HP, Sanders CJ, Mermella B, Gibas CF, Ibrahim AS, Shaw KJ, Wiederhold NP . 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 . 33722886 . 8315997 . 10.1128/AAC.02343-20 .
  5. Web site: GWT1. Stanford University. Saccharomyces Genome Database. 2022-06-28.
  6. Shaw KJ, Ibrahim AS . 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 . 33105672 . 7711534 . 10.3390/jof6040239 . free .
  7. Pfaller MA, Huband MD, Flamm RK, Bien PA, Castanheira M . 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 . 34051400 . 10.1016/j.jgar.2021.04.012 . free .
  8. Strong N, Meeks G, Sheth SA, McCullough L, Villalba JA, Tan C, Barreto A, Wanger A, McDonald M, Kan P, Shaltoni H, Campo Maldonado J, Parada V, Hassan AE, Reagan-Steiner S, Chiller T, Gold JA, Smith DJ, Ostrosky-Zeichner L . Neurovascular Complications of Iatrogenic Fusarium solani Meningitis . The New England Journal of Medicine . 390 . 6 . 522–529 . February 2024 . 38324485 . 10.1056/NEJMoa2308192 . 267547035 .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Fosmanogepix".

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