glycosylation

1-Deoxymannojirimycin hydrochloride, a selective α1,2-mannosidase inhibitor (IC50: 20 μM), also inhibits HIV-1 strains but exhibits poor antiviral activity.

Robinetin (3,3',4',5',7-Pentahydroxyflavone) exhibits potent antioxidant and antiradical activities, effectively inhibiting EYPC membrane lipid peroxidation and HbA glycosylation.

Benzyl-α-GalNAc (O-glycosylation-IN-1) is an effective inhibitor of O-glycosylation used to reduce the levels of mucin on the cell surface; it can inhibit the synthesis of O-glycosylated mucin in a human pancreatic cancer cell model. Benzyl-α-GalNAc effectively inhibits the proliferation and activation of LX-2 cells and suppresses the expression of collagen I/III, making it suitable for studies on liver fibrosis. Benzyl-α-GalNAc can be used in research on glycobiology, tumor metastasis, liver fibrosis, and chemotherapeutic sensitization.

T3Inh-1 is a potent and selective ppGalNAc-T3 inhibitor with IC50 of 7 µM. T3Inh-1 protects against breast cancer cells. T3Inh-1 reduces FGF23 hormone levels in tissue cells and mice without causing any toxic side effects.

Tunicamycin is a mixture of antibiotics that inhibit N-linked glycosylation by blocking GlcNAc phosphotransferase (GPT). Tunicamycin has antitumor activity, as well as anti-bacterial, anti-fungal, and anti-viral activity.

LY3372689 (Formulaic Ia) is an oral, highly selective, CNS-permeable O-GlcNAcase (OGA) inhibitor. LY3372689 exerts a neuroprotective effect by inhibiting OGA enzymatic activity, increasing the O-GlcNAc glycosylation level of tau protein, and thereby reducing abnormal tau phosphorylation and the formation of neurofibrillary tangles. LY3372689 can be used in research on tau-related diseases, including Alzheimer’s disease.

Pyrimidine (Metadiazine)s are heterocyclic, six-membered, nitrogen-containing carbon ring structures, with uracil, cytosine and thymine being the basal structures of ribose-containing nucleosides (uridine, cytidine, and thymidine respectively), or deoxyribose-containing deoxynucleosides, and their corresponding ribonucleotides or deoxyribonucleotides. Pyrimidines serve essential functions in human metabolism as ribonucleotide bases in RNA (uracil and cytosine), and as deoxyribonucleotide bases in DNA (cytosine and thymine), and are linked by phosphodiester bridges to purine nucleotides in double-stranded DNA, in both the nucleus and the mitochondria. Pyrimidine activated sugars are also involved in polysaccharide and phospholipid synthesis, glucuronidation in detoxification processes, glycosylation of proteins and lipids and in the recently identified novel endothelium-derived vasoactive dinucleotides.

D-Mannose (D-(+)-Mannose) is a carbohydrate. D-Mannose plays an important role in human metabolism, especially in the glycosylation of specific proteins.

D-(+)-Xylose (Wood sugar) is an aldopentose - a monosaccharide containing five carbon atoms and an aldehyde functional group. It has chemical formula C5H10O5 and is 40% as sweet as sucrose. Xylose is also found in mucopolysaccharides of connective tissue and sometimes in the urine. Xylose is the first sugar added to serine or threonine residues during proteoglycan type O-glycosylation. Therefore xylose is involved in the biosythetic pathways of most anionic polysaccharides such as heparan sulphate and chondroitin sulphate. In medicine, xylose is used to test for malabsorption by administering a xylose solution to the patient after fasting. If xylose is detected in the blood and/or urine within the next few hours, it has been absorbed by the intestines. Xylose is said to be one of eight sugars which are essential for human nutrition, the others being galactose, glucose, mannose, N-acetylglucosamine, N-acetylgalactosamine, fucose, and sialic acid. . Xylose in the urine is a biomarker for the consumption of apples and other fruits.

2,2-Dihydroxyacetic acid (Formylformic acid) is an intermediate in the glyoxalate cycle, which enables certain organisms to convert fatty acids to carbohydrates.2,2-Dihydroxyacetic acid has been found to be associated with primary hyperoxaluria, an inborn error of metabolism. As an aldehyde, glyoxalate is also highly active and can modify proteins to form advanced glycosylation products (AGEs).

Galactose is a monosaccharide and hexose sugar widely present in most living cells, primarily absorbed into the bloodstream via SGLT1 and GLUT2 transporters and metabolised through the Leloir pathway. It inhibits alglucerase activity in monkey kidney CoS-1 cells, is a key component of cellular glycosylation, and plays a crucial role in neonatal neural development.

6-Methoxytricin, a flavonoid isolated from Centella asiatica, is an inhibitor of aldose reductase (AR) and advanced glycosylation end-products (AGE), and inhibits T-cell proliferation and activation in biologic cells.

N-Desmethyltamoxifen, the principal metabolite of tamoxifen in humans, serves as an efficacious modulator of ceramide metabolism within human AML cells by inhibiting ceramide glycosylation, hydrolysis, and sphingosine phosphorylation. Although it demonstrates weak antiestrogenic properties, it acts as a protein kinase C (PKC) inhibitor with a potency ten times greater than that of tamoxifen.

Caffeic acid 4-O-glucoside (Linocaffein), a glycosylation product of Caffeic acid, reverses Aβ25-35-induced axonal atrophy and induces axonal regeneration in mouse cortical neurons, and can be used in Alzheimer's disease research.

6′SLN is a characteristic glycan found on the surface of cancer-related extracellular vesicles (EVs) and serves as the primary form of protein glycosylation within EVs. Additionally, 6′SLN, a derivative of sialic acid, interacts with hemagglutinins (HAs) from both human and avian influenza strains, making it relevant in the study of anti-influenza drugs.

L-Erythrose (L-(+)-Erythrose) is a tetrasaccharide and an aldose, and oxidizing bacteria are able to use L-Erythrose as their sole source of energy.L-Erythrose is involved in the synthesis of erythritol, and can therefore be used in glycosylation studies and to characterize erythrose reductase (ER) activity.

Kifunensine, an alkaloid discovered in Kitasatosporia kifunense, functions as a glycosylation pathway inhibitor and immunomodulator. It strongly inhibits α-mannosidase I in the Golgi apparatus and may be utilised in studies of endoplasmic reticulum stress.

Glycation-IN-1 (Compound 3) is an inhibitor of the glycosylation reaction, effectively suppressing the synthesis of the initial, intermediate, and final products of glycation reactions. It is applicable in research on various chronic diseases, including diabetes, immune inflammation, cardiovascular diseases, and neurodegenerative disorders.

LacNAc-VC-PAB-MMAE is a component of an antibody-drug conjugate (ADC). It is assembled onto the N-glycosylation site of Trastuzumab through WT Endo-S2.

NGI-235 is a selective OST-A inhibitor that specifically inhibits the NF-κB inflammatory signaling pathway by blocking TLR4 glycosylation and cell surface localization. NGI-235 can be used in research on inflammatory and immune-related diseases.

NGI-189 is a selective OST-A inhibitor. Its main mechanism is to inhibit the activity of the STT3A catalytic subunit in the OST complex, thereby reducing the N-glycosylation level of target glycoproteins. It effectively blocks the conduction of oncogenic and bypass signaling pathways, significantly downregulates the phosphorylation levels of EGFR, AKT, p70S6K and S6RP proteins, and induces cell cycle arrest and apoptosis. In non-small cell lung cancer (NSCLC) xenograft models, NGI-189 significantly inhibits tumor growth and induces tumor regression, making it a potential tool molecule for mechanism and efficacy research of EGFR-mutant non-small cell lung cancer.

Glycosyltransferase-IN-2 (Compound 20) is an inhibitor of glycosyltransferase with broad-spectrum antiviral activities against coronaviruses. It shows IC50 values of 11.3 μM for MHV, 5.5 μM for HCoV-NL63, and approximately 16.2 μM for SARS-CoV-2. This compound can interfere with coronavirus infectivity, alter viral protein glycosylation, inhibit interaction with the ACE2 receptor, and suppress secretion of cytotoxic viral particles (SC-VLP) and RNA replication. Glycosyltransferase-IN-2 is utilized in coronavirus infection research.

2DG-ODDA is a potent antitumor derivative of 2-deoxyglucose (2-DG). It induces apoptosis and reduces ATP production. 2DG-ODDA is absorbed via fatty acid and glucose transporters and cleaved by α-Mannosidase to release 2DG, thereby inhibiting N-glycosylation and disrupting cellular metabolism. It suppresses tumor growth in 4T1 murine models and is applicable in triple-negative breast cancer (TNBC) research.

(R,S)-STT3A/B-IN-1 (compound 32) is the racemic form of STT3A/B-IN-1 and functions as an STT3A/B inhibitor. It suppresses N-glycosylation (N-Glycosylation) and has potential applications in research related to viral diseases, cancer, and neurodegenerative disorders.