DEOXYGALACTONOJIRIMYCIN, HYDROCHLORIDE

Product NameDEOXYGALACTONOJIRIMYCIN, HYDROCHLORIDE
CAS108147-54-2
MFC6H13NO4
MW163.17
EINECS
MOL File108147-54-2.mol

Chemical Properties

Melting point	243-245 °C
Boiling point	361.1±42.0 °C(Predicted)
Density	1.456±0.06 g/cm3(Predicted)
storage temp.	2-8°C
pka	13.77±0.70(Predicted)

Safety Information

Hazard Codes	Xi
Risk Statements	36/37/38
Safety Statements	26-36
WGK Germany	3

MSDS

Provider	Language
SigmaAldrich	English

Usage And Synthesis

Uses

Migalastat (GR181413A free base) is an orally active α-galactosidase A molecular chaperone, with an IC50 value of 0.04 μM for human α-Gal A. Migalastat binds to the active site of certain unstable mutant forms of α-galactosidase A, facilitating their transport to the lysosome. After dissociation in the acidic environment, Migalastat enables the mutant α-galactosidase A to exhibit biological activity[1].

Definition

ChEBI: Migalastat is a member of piperidines.

brand name

Treatment of Fabry disease.

in vivo

Fabry disease is an X-linked recessive disorder caused by the deficient activity of α-galactosidase A^[2].
Migalastat (oral gavage, 3 mg/kg daily for 4 weeks) increases α-Gal A activity in heart, kidney, spleen, and liver in a dose- and time-dependently in transgenic mice that express human mutant alpha-Gal A (TgM)^[2].
Migalastat shows the half-life of less than 1 day in all major issues in TgM for 2 weeks pretreatment^[2].
Migalastat (oral gavage, 100 mg/kg daily for 28 days) to transgenic mice reduces lyso-Gb3 levels up to 64%, 59%, and 81% in kidney, heart, and skin, respectively^[3].

Animal Model:	Male nontransgenic (Non-Tg) C57BL/6 mice; transgenic mice expressing human mutant R301Q α-Gal A (TgM), α-Gal A knockout mice (KO), mice express human R301Q α-Gal A in a null background (TgM/KO)^[2]
Dosage:	3 mg/kg
Administration:	Oral gavage; every day for 4 weeks
Result:	Reduced Globotriaosylceramide (Gb3) storage remarkably in kidney of mice.

References

[1] Asano N, et al. In vitro inhibition and intracellular enhancement of lysosomal alpha-galactosidase A activity in Fabry lymphoblasts by 1-deoxygalactonojirimycin and its derivatives. Eur J Biochem. 2000 Jul;267(13):4179-86. DOI:10.1046/j.1432-1327.2000.01457.x
[2] Ishii S, et al. Preclinical efficacy and safety of 1-deoxygalactonojirimycin in mice for Fabry disease. J Pharmacol Exp Ther. 2009 Mar;328(3):723-31. DOI:10.1124/jpet.108.149054
[3] Young-Gqamana B, et al. Migalastat HCl reduces globotriaosylsphingosine (lyso-Gb3) in Fabry transgenic mice and in the plasma of Fabry patients. PLoS One. 2013;8(3):e57631. DOI:10.1371/journal.pone.0057631
[4] Welford RWD, et al. Glucosylceramide synthase inhibition with lucerastat lowers globotriaosylceramide and lysosome staining in cultured fibroblasts from Fabry patients with different mutation types. Hum Mol Genet. 2018 Oct. 27(19):3392-3403. DOI:10.1093/hmg/ddy248

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