Migalastat hydrochloride

Migalastat hydrochloride

Migalastat hydrochloride, with the CAS number 75172-81-5, is a pharmacological chaperone used primarily in the treatment of Fabry disease, a genetic disorder caused by the deficiency of the enzyme alpha-galactosidase A (alpha-Gal A). This compound is marketed under the brand name Galafold and is indicated for patients with amenable GLA variants.

Chemical Properties

• Molecular Formula: C6H13NO4·HCl
• Molecular Weight: 199.63 g/mol
• MDL Number: MFCD00269962
• EINECS: Not specified

Migalastat hydrochloride appears as a white to almost white crystalline solid and is freely soluble in aqueous media within a pH range of 1.2 to 7.5. Its pharmacological action involves binding to misfolded alpha-Gal A, stabilizing it, and facilitating its transport to lysosomes where it can effectively break down glycosphingolipids such as globotriaosylceramide (GL-3) and globotriaosylsphingosine (lyso-Gb3).

Mechanism of Action

Migalastat works by:

• Binding reversibly to the active site of alpha-Gal A.
• Stabilizing the enzyme, allowing it to reach lysosomes where it functions optimally.
• Enhancing the breakdown of accumulated substrates in patients with specific genetic mutations that lead to enzyme dysfunction.

Clinical Information

Indications

Migalastat is specifically indicated for adults with Fabry disease who have amenable GLA variants.

Pharmacokinetics

• Volume of Distribution: Ranges from 77 to 133 L.
• Half-Life: Approximately 3 to 5 hours.
• Excretion: Primarily through urine (77% of the dose) and feces (20% of the dose).

Adverse Effects

Common side effects include gastrointestinal disturbances, headache, and potential renal implications in patients with severe renal impairment.

Citations:

1. https://go.drugbank.com/drugs/DB05018
2. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=66dbd928-0f1c-48b1-a832-54e4abd9f1db
3. https://focusbiomolecules.com/migalastat-hcl-galactosidase-inhibitor-pharmacological-chaperone/
4. https://ec.europa.eu/health/documents/community-register/2016/20160526134799/anx_134799_en.pdf
5. https://pubchem.ncbi.nlm.nih.gov/compound/Migalastat-hydrochloride
6. https://www.avantorsciences.com/us/en/product/47597073/migalastat-hydrochloride-98
7. https://www.tga.gov.au/sites/default/files/auspar-migalastat-180830-pi.pdf
8. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/208623Orig1s000MultidisciplineR.pdf