Historically isolated from Kitasato kifunensine.¹ Inhibitor of class I α-mannosidases which inhibit glycoprotein processing. Inhibits human endoplasmic reticulum α-1,2-mannosidase I and Golgi Class I mannosidases IA, IB and IC with K_i values of 130 and 23 nM respectively.² Inhibition of endoplasmic reticulum a-mannosidase I activity rescues the human a-sarcoglycan R77C mutation suggesting a new pharmacological approach for limb girdle muscular dystrophy type 2D patients carrying mutations that impair a-sarcoglycan trafficking.³ Improves maturation of misfolded proteins.⁴

References/Citations

1) Iwami et al. (1987), A new immunomodulator, FR-900494: taxonomy, fermentation, isolation, and physico-chemical and biological characteristics; J.Antibiot. (Tokyo) 40 612
2) Elbein et al. (1990), Kifunensine, a potent inhibitor of the glycoprotein processing mannosidase I;  J.Biol.Chem. 265 15599
3) Bartoli et al. (2008), Mannosidase I inhibition rescues the human alpha-sarcoglycan R77C recurrent mutation;  Hum.Mol.Genet. 17 1214
4) Wang et al. (2011), Inhibition of endoplasmic reticulum-associated degradation rescues native folding in loss of function protein misfolding diseases; J.Biol.Chem. 286 43454