Migalastat hydrochlorideProduct ingredient for Migalastat

Name
Migalastat hydrochloride
Drug Entry
Migalastat

Fabry disease is a rare, progressive genetic disorder characterized by a defective GLA gene that causes a deficiency in the enzyme alpha-Galactosidase A (alpha-Gal A) Label,6,3,2. This enzyme is responsible for breaking down glycosphingolipid substrate that, when deficient in patients with Fabry disease, builds up in the blood vessels, the kidneys, the nerves, the heart, and other organs Label,6,3,4. In the U.S., it is estimated that more than 3,000 people are living with Fabry disease, and an estimated more than 50 percent of these diagnosed patients are currently untreated 3.

Migalastat (approved and sold under Amicus Therapeutics' brand name Galafold) is subsequently an oral pharmacological chaperone of alpha-Gal A for the treatment of Fabry disease in adults who have amenable GLA variants Label,6,3,4. In these patients, migalastat works by stabilizing the body’s own dysfunctional alpha-Gal A enzyme so that it can clear the accumulation of glycosphingolipid disease substrate Label,6,3,4. Globally, it is estimated that approximately 35 to 50 percent of Fabry patients may have amenable GLA variants that are treatable with migalastat 3.

Given the rarity of Fabry disease and the proportion of Fabry disease patients that could benefit from migalastat therapy, Amicus Therapeutics' brand name Galafold was approved using the Accelerated Approval pathway, under which the FDA may approve drugs for serious conditions where there is an unmet medical need and where a drug is shown to have certain effects that are reasonably likely to predict a clinical benefit to patients Label,6,3,4. A further study is required to verify and describe the clinical benefits of Galafold, and the sponsor will be conducting a confirmatory clinical trial of Galafold in adults with Fabry disease Label,6,3,4.

Additionally, Galafold was alzo granted Priority Review designation, under which the FDA’s goal is to take action on an application within six months of application filing where the agency determines that the drug, if approved, would provide a significant improvement in treating, diagnosing or preventing a serious condition over available therapies Label,6. Galafold also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases Label,6.

As of August 2018, migalastat under Amicus Therapeutics' brand name Galafold is currently approved in Australia, Canada, European Union, Israel, Japan, South Korea, Switzerland, and the United States.

Accession Number
DBSALT000828
Structure
Synonyms
Migalastat HCl
UNII
CLY7M0XD20
CAS Number
75172-81-5
Weight
Average: 199.633
Monoisotopic: 199.061135648
Chemical Formula
C6H14ClNO4
InChI Key
ZJIHMALTJRDNQI-OLALXQGDSA-N
InChI
InChI=1S/C6H13NO4.ClH/c8-2-3-5(10)6(11)4(9)1-7-3;/h3-11H,1-2H2;1H/t3-,4+,5+,6-;/m1./s1
IUPAC Name
(2R,3S,4R,5S)-2-(hydroxymethyl)piperidine-3,4,5-triol hydrochloride
SMILES
Cl.OC[C@H]1NC[C@H](O)[C@@H](O)[C@H]1O
PubChem Compound
11644097
ChemSpider
9818836
ChEMBL
CHEMBL2107355
Wikipedia
Migalastat
Predicted Properties
PropertyValueSource
Water Solubility511.0 mg/mLALOGPS
logP-2.2ALOGPS
logP-2.9Chemaxon
logS0.5ALOGPS
pKa (Strongest Acidic)12.91Chemaxon
pKa (Strongest Basic)8.06Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count5Chemaxon
Polar Surface Area92.95 Å2Chemaxon
Rotatable Bond Count1Chemaxon
Refractivity36.57 m3·mol-1Chemaxon
Polarizability15.86 Å3Chemaxon
Number of Rings1Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon