| Size | Price | |
|---|---|---|
| 10mg | ||
| 25mg | ||
| 50mg | ||
| 100mg | ||
| 250mg |
Purity: ≥98%
Migalastat (1-Deoxygalactonojirimycin, GR181413A; AT1001; trade name: Galafold) is a pharmacological chaperone acting as an α-galactosidase A (α-Gal A) inhibitor. It potently and selectively binds, stabilizes, and increases cellular levels of α-Gal A with an IC50 of 0.04 μM for human α-Gal A. Migalastat was approved by FDA in August 2018 to treat treat adults with Fabry disease. Oral administration of migalastat HCl reduces tissue GL-3 in Fabry transgenic mice, and in urine and kidneys of some FD patients. Fabry disease (FD) results from mutations in the gene (GLA) that encodes the lysosomal enzyme α-galactosidase A (α-Gal A), and involves pathological accumulation of globotriaosylceramide (GL-3) and globotriaosylsphingosine (lyso-Gb3). Oral administration of migalastat HCl to transgenic mice reduced elevated lyso-Gb3 levels up to 64%, 59%, and 81% in kidney, heart, and skin, respectively, generally equal to or greater than observed for GL-3. Furthermore, baseline plasma lyso-Gb3 levels were markedly elevated in six male FD patients enrolled in Phase 2 studies. Oral administration of migalastat HCl (150 mg QOD) reduced urine GL-3 and plasma lyso-Gb3 in three subjects (range: 15% to 46% within 48 weeks of treatment). In contrast, three showed no reductions in either substrate. These results suggest that measurement of tissue and/or plasma lyso-Gb3 is feasible and may be warranted in future studies of migalastat HCl or other new potential therapies for FD.
| ln Vitro |
With IC50 and Ki values of 0.04 μM, migalastat inhibits human lysosomal a-Gal A [1].
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| ln Vivo |
α-galactosidase A activity defects are the cause of Fabry disease, an X-linked recessive genetic illness [2]. In transgenic mice expressing human mutant α-Gal A (TgM), migalastat (oral gavage, 3 mg/kg daily for 4 weeks) enhances α-Gal A activity in the heart, kidney, spleen, and liver and demonstrates dose- and time-dependent effects. )[2]. During the first two weeks of treatment, Migasalstat demonstrated half-lives of less than one day for all key issues in TgM [2]. In transgenic mice, migastat (oral gavage, 100 mg/kg daily for 28 days) decreased the levels of lyso-Gb3 in the kidney, heart, and skin by as much as 64%, 59%, and 81%, in that order [3].
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| Cell Assay |
Cell Viability Assay [4]
Cell Types: EHK Cell Mutated α-Gal A Tested Concentrations: 10 μM Incubation Duration: 9 days Experimental Results: Gb3 accumulation and lysosomal volume reduction. |
| Animal Protocol |
Animal/Disease Models: Male non-transgenic (Non-Tg) C57BL/6 mice; transgenic mice expressing human mutant R301Q α-Gal A (TgM), α-Gal A knockout mice (KO), in null background Mice expressing human R301Q α-Gal A (TgM/KO) [2]
Doses: 3 mg/kg Route of Administration: po (oral gavage); one time/day for 4 weeks Experimental Results: Triacylceramide (Gb3) in mouse kidneys Storage is Dramatically diminished. |
| 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.
[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. [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. [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. |
| Molecular Formula |
C6H13NO4
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|---|---|
| Molecular Weight |
199.63266
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| CAS # |
108147-54-2
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| Related CAS # |
Migalastat hydrochloride;75172-81-5
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| SMILES |
[C@@H]1([C@H]([C@H](NC[C@@H]1O)CO)O)O
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| InChi Key |
LXBIFEVIBLOUGU-DPYQTVNSSA-N
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| InChi Code |
1S/C6H13NO4/c8-2-3-5(10)6(11)4(9)1-7-3/h3-11H,1-2H2/t3-,4+,5+,6-/m1/s1
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| Chemical Name |
D-Galactitol, 1,5-dideoxy-1,5-imino-
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| Synonyms |
Amigal, DDIG, Migalastat 1-Deoxygalactonojirimycin
1-Deoxygalactostatin AT1001 AT 1001 AT-1001 GR181413A GR 181413A
GR-181413A Galafold
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.0093 mL | 25.0463 mL | 50.0927 mL | |
| 5 mM | 1.0019 mL | 5.0093 mL | 10.0185 mL | |
| 10 mM | 0.5009 mL | 2.5046 mL | 5.0093 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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