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

^ "What we do : Basilea".
^ 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.
^ "Fosmanogepix - Amplyx Pharmaceuticals". AdisInsight. Springer Nature Switzerland AG. Retrieved June 27, 2022.
^ 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.
^ "GWT1". Saccharomyces Genome Database. Stanford University. Retrieved 2022-06-28.
^ ^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.
^ 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.
^ 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. PMID 38324485. S2CID 267547035.

[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.

[Shaw-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. PMID 38324485. S2CID 267547035.

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