fosmanogepix
{{Short description|Chemical compound}}
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| legal_status = Investigational
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| 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
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Fosmanogepix is an experimental antifungal drug being developed by Amplyx Pharmaceuticals (now currently by Pfizer and Basilea{{cite web | url=https://www.basilea.com/what-we-do | title=What we do : Basilea }}{{cite journal | vauthors = 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 | title = The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin | journal = Drugs | volume = 81 | issue = 15 | pages = 1703–1729 | date = October 2021 | pmid = 34626339 | pmc = 8501344 | doi = 10.1007/s40265-021-01611-0 }}) It is being investigated for its potential to treat various fungal infections including aspergillosis, candidaemia, and coccidioidomycosis.{{cite web | url = https://adisinsight.springer.com/drugs/800043868 | title = Fosmanogepix - Amplyx Pharmaceuticals | work = AdisInsight | publisher = Springer Nature Switzerland AG | access-date = June 27, 2022 }}
Fosmanogepix is a prodrug and is converted into the active drug form, manogepix in vivo.{{cite journal | vauthors = Badali H, Patterson HP, Sanders CJ, Mermella B, Gibas CF, Ibrahim AS, Shaw KJ, Wiederhold NP | title = Manogepix, the Active Moiety of the Investigational Agent Fosmanogepix, Demonstrates In Vitro Activity against Members of the Fusarium oxysporum and Fusarium solani Species Complexes | journal = Antimicrobial Agents and Chemotherapy | volume = 65 | issue = 6 | date = May 2021 | pmid = 33722886 | pmc = 8315997 | doi = 10.1128/AAC.02343-20 }} Manogepix targets the enzyme GWT1 (Glycosylphosphatidylinositol-anchored Wall protein Transfer 1{{cite web|url=https://www.yeastgenome.org/locus/S000003627|title=GWT1|publisher= Stanford University|website=Saccharomyces Genome Database|access-date=2022-06-28}}), an enzyme in the glycosylphosphatidylinositol biosynthesis pathway.{{cite journal | vauthors = Shaw KJ, Ibrahim AS | title = Fosmanogepix: A Review of the First-in-Class Broad Spectrum Agent for the Treatment of Invasive Fungal Infections | journal = Journal of Fungi | volume = 6 | issue = 4 | page = 239 | date = October 2020 | pmid = 33105672 | pmc = 7711534 | doi = 10.3390/jof6040239 | doi-access = free }} 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.{{cite journal | vauthors = Pfaller MA, Huband MD, Flamm RK, Bien PA, Castanheira M | title = 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 = Journal of Global Antimicrobial Resistance | volume = 26 | pages = 117–127 | date = September 2021 | pmid = 34051400 | doi = 10.1016/j.jgar.2021.04.012 | doi-access = free }}
In 2023, the drug was given a compassionate use authorization for four patients with Fusarium solani meningitis.{{cite journal | vauthors = 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 | title = Neurovascular Complications of Iatrogenic Fusarium solani Meningitis | journal = The New England Journal of Medicine | volume = 390 | issue = 6 | pages = 522–529 | date = February 2024 | pmid = 38324485 | doi = 10.1056/NEJMoa2308192 | s2cid = 267547035 | pmc = 11905984 }}