AFEGOSTAT

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C6H13NO3
Molecular Weight	147.1723
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC[C@H]1CNC[C@@H](O)[C@@H]1O

InChI

InChIKey=QPYJXFZUIJOGNX-HSUXUTPPSA-N

InChI=1S/C6H13NO3/c8-3-4-1-7-2-5(9)6(4)10/h4-10H,1-3H2/t4-,5-,6-/m1/s1

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Description
Sources: https://adisinsight.springer.com/drugs/800023168 | http://xqdoc.imedao.com/165d869871d163a33fce5ca6.pdf | https://www.ncbi.nlm.nih.gov/pubmed/25037721

Amicus Therapeutics was investigating afegostat (isofagomine; Plicera; HGT-3410; AT-2101), an orally available pharmacological chaperone molecule, which binds to glucocerebrosidase (Gba) and stimulates proper folding and trafficking of the enzyme, for the potential treatment of Parkinsons disease(PD) and Gaucher disease. Afegostat specifically and reversibly binds GCase in the ER with highaffinity; this stabilizes the active form of the enzyme in the ER and increases trafficking of GCase to lysosomes. In 2006, Orphan Drug designations were granted in the U.S. and E.U. in 2006 and 2007, respectively. However, this research has been discontinued.

CNS Activity

Originator

Approval Year

PubMed

Title	Date	PubMed

Patents

Sample Use Guides

In Vivo Use Guide

For the first 2 weeks, afegostat tartrate was administered orally at a dose of 225 milligrams (mg) once daily (QD) for 7 consecutive days, followed by no study medication for 7 consecutive days. After 2 weeks, participants then took 225 mg afegostat tartrate QD for 3 consecutive days, followed by no study medication for 4 consecutive days. This 3-days-on/4-days-off treatment regimen was followed for 22 weeks.

Route of Administration: Oral

In Vitro Use Guide

Afegostat inhibits GCase with K(i) ~30 nM for wild-type and mutant enzymes (N370S and V394L)

Name

Type

Language

AFEGOSTAT

Official Name

English

ISOFAGOMINE

Common Name

English

(3R,4R,5R)-5-(Hydroxymethyl)piperidine-3,4-diol

Systematic Name

English

3,4-PIPERIDINEDIOL, 5-(HYDROXYMETHYL)-, (3R,4R,5R)-

Systematic Name

English

ISOFAGOMINE [MI]

Common Name

English

Afegostat [WHO-DD]

Common Name

English

afegostat [INN]

Common Name

English

AFEGOSTAT [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C87006