Kifunensine is a potent and selective inhibitor of class I α-mannosidases and may serve as a key inhibitor of glycoprotein biosynthesis[1]. 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[1]. 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[2,3].
References:
[1]. Hering K W, Karaveg K, Moremen K W, et al. A Practical Synthesis of Kifunensine Analogues as Inhibitors of Endoplasmic Reticulum alpha-Mannosidase I. Journal of Organic Chemistry, 2005, 70(24): p.9892-9904.
[2]. Bartoli M, Gicquel E, Barrault L, et al. Mannosidase I inhibition rescues the human α-sarcoglycan R77C recurrent mutation. Human Molecular Genetics, 2008, 17(9): 1214-1221.
[3]. 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, 2012, 33(2): 429-439.
