| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| Other Sizes |
| Targets |
Ac5GalNTGc targets the biosynthesis of mucin-type O-linked glycans. Mucin-type O-glycosylation is a post-translational modification that involves the addition of N-acetylgalactosamine (GalNAc) to serine or threonine residues of proteins, catalyzed by a family of polypeptide GalNAc transferases (ppGalNAcTs). This type of glycosylation is important for the structure and function of mucins and other glycoproteins, and it plays roles in cell adhesion, immune recognition, and cancer metastasis. Ac5GalNTGc is a hexosamine analog that inhibits the biosynthesis of mucin-type O-glycans by interfering with the transfer of GalNAc to proteins. By inhibiting O-glycosylation, the compound reduces the expression of sialyl-Lewis-X, a carbohydrate antigen that is a ligand for selectins. This inhibition of selectin-mediated adhesion is the downstream functional consequence of Ac5GalNTGc's activity.
|
|---|---|
| ln Vitro |
In vitro, Ac5GalNTGc inhibits mucin-type O-linked glycosylation biosynthesis. This inhibition leads to reduced expression of sialyl-Lewis-X on leukocytes. Sialyl-Lewis-X is a carbohydrate antigen that serves as a ligand for L-selectin and P-selectin, which are adhesion molecules involved in leukocyte trafficking and inflammation. By reducing sialyl-Lewis-X expression, Ac5GalNTGc inhibits L-/P-selectin-mediated rolling of leukocytes under flow conditions and inhibits P-selectin-dependent leukocyte-platelet adhesion. These in vitro activities demonstrate the compound's ability to modulate cell adhesion processes that are important for inflammation and cancer metastasis. The peracetylated form of Ac5GalNTGc enhances cell permeability, allowing the compound to enter cells where it is deacetylated to its active form. The compound is used as a research tool to study the role of O-glycosylation in cell adhesion and inflammation.
|
| ln Vivo |
In vivo activity of Ac5GalNTGc has not been extensively reported in the available literature. Based on its mechanism of action, the compound would be expected to have anti-inflammatory and anti-metastatic effects in vivo by inhibiting selectin-mediated leukocyte adhesion and recruitment. However, specific animal model studies, dosing regimens, and quantitative outcomes have not been reported. The compound's peracetylated form is designed to enhance cell permeability and oral bioavailability, suggesting that it may be suitable for in vivo administration. Potential applications could include studies of inflammatory diseases, such as atherosclerosis or inflammatory bowel disease, and studies of cancer metastasis, where selectin-mediated adhesion plays a role. Further in vivo studies would be required to characterize its efficacy, safety, and pharmacokinetic properties.
|
| Enzyme Assay |
In vitro enzyme or receptor binding assay protocols for Ac5GalNTGc are not directly applicable, as the compound is a metabolic inhibitor that interferes with glycosylation rather than a direct enzyme inhibitor in the traditional sense. However, the activity of Ac5GalNTGc can be assessed by measuring its effects on O-glycan biosynthesis and sialyl-Lewis-X expression. A standard protocol would involve treating cells (e.g., leukocytes or cancer cells) with varying concentrations of Ac5GalNTGc (typically 1-100 μM) for a defined period (e.g., 24-72 hours). Cells are then harvested, and O-glycan biosynthesis is assessed by metabolic labeling with radioactive or fluorescent sugar precursors followed by analysis of labeled glycoproteins by SDS-PAGE or lectin blotting. Sialyl-Lewis-X expression can be measured by flow cytometry using specific antibodies (e.g., anti-sialyl-Lewis-X monoclonal antibodies). The inhibition of selectin-mediated adhesion can be assessed using cell adhesion assays under flow conditions.
|
| Cell Assay |
In vitro cell-based assay protocols for Ac5GalNTGc typically involve assessing its effects on O-glycosylation, sialyl-Lewis-X expression, and selectin-mediated adhesion in cultured cells. A standard protocol for assessing O-glycosylation inhibition involves treating cells (e.g., leukocytes such as HL-60 or THP-1 cells, or cancer cell lines) with varying concentrations of Ac5GalNTGc (typically 1-100 μM) for 24-72 hours. Cells are then harvested, and O-glycan biosynthesis is assessed by lectin blotting (e.g., using peanut agglutinin or other lectins that recognize O-glycans) or by metabolic labeling with 3H-galactosamine or other sugar precursors. Sialyl-Lewis-X expression is measured by flow cytometry using anti-sialyl-Lewis-X antibodies. For adhesion assays, cells treated with Ac5GalNTGc are perfused over selectin-coated surfaces or endothelial cell monolayers under flow conditions, and the number of rolling or adherent cells is quantified. P-selectin-dependent leukocyte-platelet adhesion can be assessed in static or flow adhesion assays.
|
| Animal Protocol |
In vivo animal experimental protocols for Ac5GalNTGc have not been extensively reported. Based on its mechanism as an inhibitor of O-glycosylation and selectin-mediated adhesion, potential studies might involve administering the compound to animal models of inflammation or cancer metastasis. A hypothetical protocol for studying its anti-inflammatory effects would involve administering Ac5GalNTGc orally or intraperitoneally to mice in models of peritonitis, colitis, or other inflammatory conditions, at doses determined from preliminary studies. Endpoints would include leukocyte infiltration into inflamed tissues, levels of inflammatory cytokines, and histological assessment of inflammation. For cancer metastasis studies, the compound could be administered in models of tumor metastasis, and endpoints would include the number of metastatic foci in target organs. However, specific published protocols are not available.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Ac5GalNTGc have not been characterized in published studies. The peracetylated form of the compound is designed to enhance cell permeability and potentially oral bioavailability by masking the hydrophilic sugar moieties with acetyl groups. Once inside cells, the acetyl groups are removed by esterases to release the active compound. This prodrug strategy is commonly used for carbohydrate-based inhibitors to improve their pharmacokinetic properties. However, specific PK parameters such as half-life, Cmax, AUC, bioavailability, volume of distribution, and clearance have not been reported. The compound's metabolism, protein binding, and routes of elimination remain uncharacterized. Further pharmacokinetic studies would be required to understand its absorption, distribution, metabolism, and excretion profile.
|
| Toxicity/Toxicokinetics |
Toxicological data for Ac5GalNTGc are limited, as the compound is intended for research use only and has not undergone systematic toxicity testing. No acute toxicity (LD50), subchronic toxicity, genotoxicity, or reproductive toxicity studies have been reported specifically for this compound. As with all research chemicals, appropriate safety precautions should be taken when handling the compound, including working in a fume hood, wearing appropriate personal protective equipment, and avoiding inhalation, ingestion, or skin contact. The compound is not intended for human use. Researchers should consult the material safety data sheet (MSDS) for specific safety information and handling recommendations.
|
| References |
|
| Additional Infomation |
Ac5GalNTGc is a research-grade compound that functions as a potent inhibitor of mucin-type O-linked glycosylation biosynthesis. It is a peracetylated C-2 thioacetyl-substituted GalNAc analog (hexosamine analog) that inhibits O-glycan biosynthesis. The compound reduces leukocyte sialyl-Lewis-X expression, inhibits L-/P-selectin-mediated rolling under flow, and inhibits P-selectin-dependent leukocyte-platelet adhesion. It is used in research on cell adhesion, inflammation, and cancer metastasis. Ac5GalNTGc has not entered clinical trials and is not approved for any therapeutic indication. Its mechanism of action involves inhibition of mucin-type O-glycosylation, leading to reduced expression of selectin ligands and inhibition of selectin-mediated cell adhesion. The compound is available exclusively for research purposes and is not intended for diagnostic, therapeutic, or human applications.
|
| Molecular Formula |
C18H25NO11S
|
|---|---|
| Molecular Weight |
463.46
|
| Appearance |
White to off-white solid powder
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO :~100 mg/mL (~215.77 mM; with sonication)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.39 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one),clear solution.
For example, if 1 mL of working solution is to be prepared,you can add 100 μL of 25.0 mg/mL clear DMSO stock solution and add it to 400 μL PEG300 and mix well. Then add 50 μL Tween-80 to the above system and mix well. Then continue to add 450 μL of physiological saline to make up to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.39 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one),clear solution. For example, if 1 mL of working solution is to be prepared,you can add 100 μL of 25.0 mg/mL clear DMSO stock solution and add it to 900 μL of 20% SBE-β-CD saline solution and mix well. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.39 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one),clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1577 mL | 10.7884 mL | 21.5768 mL | |
| 5 mM | 0.4315 mL | 2.1577 mL | 4.3154 mL | |
| 10 mM | 0.2158 mL | 1.0788 mL | 2.1577 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
