Kifunensine (Synonyms: FR900494)

Kifunensine was originally isolated from the actinomycete Kitasatosporia kifunensine No. 9482 and shown to be a weak inhibitor of aryl mannosidase.[1],[2] It has since been shown to be a potent and selective inhibitor of class I α-mannosidases and may serve as a key inhibitor of glycoprotein biosynthesis.[3] Kifunensine inhibits both human endoplasmic reticulum α-1,2-mannosidase I and members of the Golgi subfamily of the class I mannosidases (Golgi α-mannosidase IA, IB, and IC) exhibiting Ki values of 130 and 23 nM, respectively. It also inhibits mung bean α-1,2-mannosidase I with an IC50 value of 20-50 nM.3 Kifunensine can be used to block α-mannosidase I activity at the endoplasmic reticulum (ER), preventing the removal of desired mutated proteins through ER quality control mechanisms.[4],[5]

Reference:
[1]. Iwami, M., Nakayama, O., Terano, H., et al. A new immunomodulator, FR-900494: Taxonomy, fermentation, isolation, and physico-chemical and biological characteristics. Journal of Antibiotics XL(5), 612-622 (1987).
[2]. Kayakiri, H., Takase, S., Shibata, T., et al. Structure of kifunensine, a new immunomodulator isolated from an actinomycete. The Journal of Organic Chemistry 54, 4015-4016 (1989).
[3]. Hering, K.W., Karaveg, K., Moremen, K.W., et al. A practical synthesis of kifunensine analogues as inhibitors of endoplasmic reticulum α-mannosidase I. The Journal of Organic Chemistry 70, 9892-9904 (2005).
[4]. Bartoli, M., Gicquel, E., Barrault, L., et al. Mannosidase I inhibition rescues the human α-sarcoglycan R77C recurrent mutation. Human Molecular Genetics 17(9), 1214-1221 (2008).
[5]. Soheili, T., Gicquel, E., Poupiot, J., et al. Rescue of sarcoglycan mutations by inhibition of endoplasmic reticulum quality control is associated with minimal structural modifications. Human Mutation 33(2), 429-439 (2012).