GnT-VB Inhibitors

Swainsonine is an alkaloid known to inhibit Golgi alpha-mannosidase II, which is necessary for the processing of N-linked glycans. As GnT-VB is involved in the glycosylation process by adding N-acetylglucosamine to N-glycans, inhibition of glycan processing by Swainsonine will block the substrate availability for GnT-VB, thereby inhibiting its function.

Kifunensine is a mannose 1-phosphate inhibitor that impairs the mannosidase I enzyme in the N-glycosylation pathway. By hindering the early processing of N-glycans, Kifunensine indirectly prevents the formation of the complex glycans that GnT-VB would typically modify, thus inhibiting GnT-VBs function indirectly by substrate depletion.

1-Deoxymannojirimycin is an iminosugar that acts as a competitive inhibitor of alpha-mannosidases. By inhibiting these enzymes, the processing of N-linked glycans is disrupted. This results in a reduced availability of the mature glycan structures that GnT-VB requires for its enzymatic activity, functionally inhibiting GnT-VB.

This compound is a specific inhibitor of β1,4-galactosyltransferase. Inhibition of this enzyme disrupts the proper formation of D-galactose containing N-glycans, which are potential substrates for GnT-VB. Therefore, GnT-VB is functionally inhibited due to the lack of suitable glycan substrates.

Castanospermine is a glucosidase inhibitor which disrupts the processing of N-linked glycans in the endoplasmic reticulum. By impeding the trimming of glucose residues from the nascent glycan chains, it indirectly prevents the proper maturation of glycans that GnT-VB would normally act upon, thereby inhibiting its function.

Deoxynojirimycin is another iminosugar that functions as a competitive inhibitor of several glycosidases. Through its action, it causes a decrease in the processing and maturation of N-linked oligosaccharides that are necessary for GnT-VB activity, leading to a functional inhibition of GnT-VB.

Celgosivir is a prodrug of the iminosugar castanospermine and inhibits α-glucosidases I and II. By blocking these enzymes, celgosivir prevents the proper folding and processing of N-glycans which are essential for GnT-VB activity, thus indirectly inhibiting the function of GnT-VB.

Isofagomine is an inhibitor of β-glucocerebrosidase and has been shown to also inhibit other glycosidases. This inhibition can lead to an accumulation of glycoconjugates and altered trafficking within the Golgi, where GnT-VB functions, thereby indirectly inhibiting the enzymatic activity of GnT-VB.

NB-DNJ is an iminosugar that acts as a competitive inhibitor of glucosylceramide synthase and various glycosidases. Through its action, it disrupts the production and processing of glycosphingolipids and N-linked glycans, which can lead to an indirect inhibition of GnT-VB by limiting its glycan substrates.