ChemicalBook CAS DataBase List 2091769-17-2

2091769-17-2

Name	Fosmanogepix
CAS	2091769-17-2
Molecular Formula	C22H21N4O6P
MDL Number	MFCD32690090
Molecular Weight	468.41
MOL File	2091769-17-2.mol

Chemical Properties

form	Solid
color	White to yellow

Hazard Information

Uses

Fosmanogepix (APX001) is a broad-spectrum agent against invasive fungal infections. Fosmanogepix (APX001) targets the conserved Gwt1 enzyme required for the localization of glycosylphosphatidylinositol-anchored mannoproteins in fungi. This inhibition prevents the appropriate localization of cell wall mannoproteins, which compromises cell wall integrity, biofilm formation, germ tube formation, and fungal growth. Fosmanogepix (APX001) can be used for invasive fungal infections research[1].

in vivo

Fosmanogepix (APX001) (390 mg/kg for Oral gavage, thrice daily) reduced the fungal burden in mouse cryptococcal meningitis (CM) model^[1].
Fosmanogepix (APX001) (100 mg/kg for Oral gavage) is the driver of efficacy in CD-1 mice^[1].

Animal Model:	murine model of cryptococcal meningitis^[1]
Dosage:	390 mg/kg
Administration:	Oral gavage (p.o.)
Result:	Observed significant differences (P < 0.05) fungal burden and reduced the fungal burden compared to untreated control in the lung tissue. Reduced the fungal burden of 0.78 log₁₀ CFU/g compared with control group in brain tissue.

Animal Model:	CD-1 mice^[1]
Dosage:	100 mg/kg
Administration:	Intraperitoneal injection (i.p.)
Result:	Extended the half-life of the active moiety, APX001A, from 1.3 to 8.8 h, resulting in a 9-fold increase in the area under the curve (AUC).

References

[1] Shaw KJ, et al. In Vitro and In Vivo Evaluation of APX001A/APX001 and Other Gwt1 Inhibitors against Cryptococcus. Antimicrob Agents Chemother. 2018 Jul 27;62(8). pii: e00523-18. DOI:10.1128/AAC.00523-18
[2] Gebremariam T, et al. APX001 Is Effective in the Treatment of Murine Invasive Pulmonary Aspergillosis. Antimicrob Agents Chemother. 2019 Jan 29;63(2). pii: e01713-18. DOI:10.1128/AAC.01713-18
[3] Shaw KJ, et al. In Vitro and In Vivo Evaluation of APX001A/APX001 and Other Gwt1 Inhibitors against Cryptococcus. Antimicrob Agents Chemother. 2018 Jul 27;62(8):e00523-18. DOI:10.1128/AAC.00523-18

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