Migalastat

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]. IC50 & Target:IC50: 0.04 μM (human α-Gal A)^[1];
Ki: 0.04 μM (human α-Gal A)^[1] In Vitro: Migalastat inhibits human lysosomal a-Gal A with IC₅₀ and K_i values of 0.04 μM^[1]. 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].