Glycosidase Inhibitor

Kifunensine, a potent and selective inhibitor of class I α-mannosidases isolated from Actinomycete, prevents α-mannosidases I from trimming mannose residues on glycoproteins. Kifunensine inhibits ERAD.

Conduritol B epoxide is an irreversible covalently bound acid β-glucosidase (GCase) inhibitor.

Acarbose (BAY g 5421), antihyperglycemic agent, is an orally active alpha-glucosidase inhibitor (IC₅₀=11 nM). Acarbose can potentiate the hypoglycemic effects of sulfonylureas or insulin.

Gallacetophenone is an inhibitor of α-glucosidase with an IC₅₀ value of 408.6 μM. When combined with 1-Deoxynojirimycin (HY-14860), Gallacetophenone exhibits synergistic inhibitory effects on mammalian α-glucosidase at high concentrations. Gallacetophenone can be used in the study of diseases such as type 2 diabetes.

Nagstatin is a naturally derived competitive inhibitor of N-acetyl-β-D-glucosaminidase (NAG-ase), with an IC₅₀ of 0.0012 μg/mL and a K_i of 1.7×10^-8 M against porcine-derived enzyme. Nagstatin enhances cellular immune responses in normal mice and reactivates suppressed cellular immune responses in tumor-bearing mice. Nagstatin can be used in the research of various diseases such as diabetes and leukemia.

Fucoidan, a biologically active polysaccharide, is an efficient inhibitor of α-amylase and α-glucosidase. Anticoagulant, antitumor, antioxidant and antisteatotic activities.

3,4-Dicaffeoylquinic acid (3,4-Di-O-caffeoylquinic acid), naturally isolated from Laggera alata, has antioxidative, DNA protective, neuroprotective and hepatoprotective properties. 3,4-Dicaffeoylquinic acid exerts apoptosis-mediated cytotoxicity and α-glucosidase inhibitory effects. 3,4-Dicaffeoylquinic acid possesses a unique mechanism of anti-influenza viral activity, that is, enhancing viral clearance by increasing TRAIL.

OGT 2115 is a potent, cell-permeable and orally active heparanase inhibitor with an IC₅₀ of 0.4 μM. OGT 2115 has anti-angiogenic properties (IC₅₀ of 1 μM). OGT 2115 also inhibits heparan sulfate degradation activity.

4,5-Dicaffeoylquinic acid (Isochlorogenic acid C) is an antioxidant, can be isolated from Gynura divaricata and Laggera alata. 4,5-Dicaffeoylquinic acid reduces islet cell apoptosis and improves pancreatic function in type 2 diabetic mice, and has obvious inhibitory activities against yeast α-glucosidase. 4,5-Dicaffeoylquinic acid inhibits prostate cancer cells through cell cycle arrest. 4,5-Dicaffeoylquinic acid also has anti-apoptotic, anti-injury and anti-hepatitis B virus effects.

1-Deoxynojirimycin (Duvoglustat) is a potent and orally active α-glucosidase inhibitor. 1-Deoxynojirimycin suppresses postprandial blood glucose and is widely used for diabetes mellitus. 1-Deoxynojirimycin possesses antihyperglycemic, anti-obesity, and antiviral features.

Castanospermine is a natural alkaloid that can be extracted from black beans or the Moreton Bay chestnut tree (Castanospermum australae). Castanospermine is an α/ β-glucosidase inhibitor. Castanospermine has anti-inflammatory, antiviral replication and anti-metastatic effects on prostate cancer. Castanospermine can be used as an immunosuppressant to prevent transplant rejection.

K284-6111 is a high-affinity and orally active CHI3L1 inhibitor, and inhibits CHI3L1 expression. K284-6111 inhibits ERK and NF-κB pathway. K284-6111 suppresses nuclear translocation of p50 and p65, and phosphorylation of IκB. K284-6111 improves memory dysfunction by alleviating amyloidogenesis and neuroinflammation, with the reduction of inflammatory proteins (eg: iNOS, COX-2, GFAP, and Iba-1). K284-6111 reduces atopic-like skin inflammation and inhibits LPS (HY-D1056) -induced liver injury. K284-6111 can be used for the study of Alzheimer's diseases and sepsis like hepatic injury.

D-(-)-Quinic acid scavenges hydrogen peroxide (IC₅₀=87.11 μg/mL) and exhibits antioxidant activity. D-(-)-Quinic acid is the inhibitor for MAO and α-Glucosidase (IC₅₀ =93.75 μg/mL). D-(-)-Quinic acid is orally active.

Miglitol (BAY-m1099) is an orally active antidiabetic compound that inhibits the breakdown of glycoconjugates into glucose. Miglitol inhibits glycoside hydrolase enzymes called α-glucosidases. Miglitol inhibits oxidative stress-induced apoptosis and mitochondrial ROS over-production in endothelial cells by enhancement of AMP-activated protein kinase. Dietary supplementation with Miglitol from pre-onset stage in OLETF rats delays the onset and development of diabetes and preserves the insulin secretory function of pancreatic islets.

Fagomine is a mild glycosidase inhibitor. The K_i of the iminosugar Fagomine is 4.8 μM, 39 μM, and 70 μM for Amyloglucosidase (A.niger), β-Glucosidase (bovine), and Isomaltase (yeast), respectively.

Rebaudioside A is an orally effective steviol glycoside with high sweetness. Rebaudioside A acts as an inhibitor of α-glucosidase with an IC₅₀ value of 35.01 μg/mL. Rebaudioside A increases the ATP/ADP ratio in β cells in a glucose-dependent manner, thereby inhibiting KATP channels, leading to membrane depolarization, calcium influx, and ultimately stimulating insulin secretion. Rebaudioside A activates the SREBP signaling pathway by inhibiting HMGCR, the rate-limiting enzyme in cholesterol synthesis, resulting in increased expression of LDLR on the cell surface, thus promoting the uptake of LDL-C in the blood. Rebaudioside A can be used for studies on blood glucose and lipid regulation as well as anti-obesity.

Docosapentaenoic acid (22n-3) is a component of phospholipids. Docosapentaenoic acid 22n-3 has inhibitory activity against α-amylase and α-glucosidase, with IC₅₀s value of 17 μg/mL and 22 μg/mL, respectively. Docosapentaenoic acid 22n-3 increases cell vitality. Docosapentaenoic acid 22n-3 has a weak anti-inflammatory effect.

Migalastat (GR181413A free base) hydrochloride 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.

Afegostat is a pharmacological chaperone, which specifically and reversibly binds acid-β-glucosidase (GCase) in the endoplasmic reticulum (ER) with high affinity.

Glucosylsphingosine (lyso-Gb1) is a deacylated form of glucosylceramide with neurotoxicity and is also a noncompetitively inhibitor of glucocerebrosidase with a K_i value of 30 μM. Glucosylsphingosine is promising for research of Krabbe and Gaucher disease.