| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Tri-GalNAc(OAc)₃ targets the Asialoglycoprotein Receptor (ASGPR). ASGPR is an endocytic receptor highly expressed on hepatocytes that specifically recognizes and binds glycoproteins with terminal galactose or N-acetylgalactosamine residues. The trivalent structure of Tri-GalNAc enables multivalent binding to ASGPR, achieving high-affinity targeting.
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|---|---|
| ln Vitro |
- Protein Degradation Activity: As the ligand component of LYTACs, Tri-GalNAc significantly reduces target protein (e.g., EGFR, HER2) levels and inhibits downstream signaling pathways, such as EGFR-mediated Akt and MAPK signals.
- Antitumor Activity: In liver cancer cell models, Tri-GalNAc-based LYTACs degrade carcinogenic membrane proteins and inhibit tumor cell proliferation. |
| Cell Assay |
- Protein Degradation Assay: Hepatocellular carcinoma cells are seeded and treated with Tri-GalNAc-conjugated LYTAC compounds. Target protein (e.g., EGFR, HER2) degradation is assessed by Western Blot.
- Cell Proliferation Inhibition Assay: In liver cancer cell models, cells are treated with Tri-GalNAc-LYTAC, and cell viability changes are evaluated using MTT or CCK-8 assays. |
| References | |
| Additional Infomation |
Selective protein degradation platforms have created new opportunities for therapeutic development and biological research. The first lysosome-targeting chimeras (LYTACs) promoted the degradation of extracellular and membrane proteins by bridging a target protein to the cation-independent mannose-6-phosphate receptor (CI-M6PR). In this study, we developed LYTACs that engage the asialoglycoprotein receptor (ASGPR), a liver-specific lysosome-targeting receptor, to degrade extracellular proteins in a cell-type-specific manner. We conjugated binders to a triantennary N-acetylgalactosamine (tri-GalNAc) motif that binds ASGPR, thereby driving protein downregulation. Degradation of the epidermal growth factor receptor (EGFR) by GalNAc-LYTAC attenuated EGFR signaling compared to inhibition with an antibody alone. Furthermore, we demonstrated that a LYTAC composed of a 3.4-kDa peptide binder linked to a tri-GalNAc ligand degrades integrins and reduces cancer cell proliferation. The use of a single tri-GalNAc ligand for site-specific conjugation on antibody scaffolds improved the pharmacokinetic profile of GalNAc-LYTACs in vivo. Thus, GalNAc-LYTACs represent a promising approach for cell-type-restricted protein degradation.
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| Molecular Formula |
C79H128N10O36
|
|---|---|
| Molecular Weight |
1793.90704536438
|
| Exact Mass |
1792.849
|
| Elemental Analysis |
C, 52.89; H, 7.19; N, 7.81; O, 32.11
|
| CAS # |
1159408-64-6
|
| Related CAS # |
1159408-65-7
|
| PubChem CID |
134511957
|
| Appearance |
White to off-white solid powder
|
| LogP |
-5.9
|
| Hydrogen Bond Donor Count |
10
|
| Hydrogen Bond Acceptor Count |
37
|
| Rotatable Bond Count |
69
|
| Heavy Atom Count |
125
|
| Complexity |
3140
|
| Defined Atom Stereocenter Count |
15
|
| SMILES |
O([C@H]1[C@H]([C@@H](COC(=O)C)O[C@@H](OCCCCC(=O)NCCCNC(=O)CCOCC(N)(COCCC(=O)NCCCNC(=O)CCCCO[C@@H]2O[C@H](COC(=O)C)[C@H](OC(=O)C)[C@H](OC(=O)C)[C@H]2NC(=O)C)COCCC(=O)NCCCNC(=O)CCCCO[C@@H]2O[C@H](COC(=O)C)[C@H](OC(=O)C)[C@H](OC(=O)C)[C@H]2NC(=O)C)[C@@H]1NC(=O)C)OC(=O)C)C(=O)C
|
| InChi Key |
VGHVGBJYGYFWED-PNPDLPPQSA-N
|
| InChi Code |
InChI=1S/C79H128N10O36/c1-46(90)87-67-73(120-55(10)99)70(117-52(7)96)58(40-114-49(4)93)123-76(67)111-34-16-13-22-61(102)81-28-19-31-84-64(105)25-37-108-43-79(80,44-109-38-26-65(106)85-32-20-29-82-62(103)23-14-17-35-112-77-68(88-47(2)91)74(121-56(11)100)71(118-53(8)97)59(124-77)41-115-50(5)94)45-110-39-27-66(107)86-33-21-30-83-63(104)24-15-18-36-113-78-69(89-48(3)92)75(122-57(12)101)72(119-54(9)98)60(125-78)42-116-51(6)95/h58-60,67-78H,13-45,80H2,1-12H3,(H,81,102)(H,82,103)(H,83,104)(H,84,105)(H,85,106)(H,86,107)(H,87,90)(H,88,91)(H,89,92)/t58-,59-,60-,67-,68-,69-,70+,71+,72+,73-,74-,75-,76-,77-,78-/m1/s1
|
| Chemical Name |
[(2R,3R,4R,5R,6R)-5-acetamido-6-[5-[3-[3-[3-[3-[3-[5-[(2R,3R,4R,5R,6R)-3-acetamido-4,5-diacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxypentanoylamino]propylamino]-3-oxopropoxy]-2-[[3-[3-[5-[(2R,3R,4R,5R,6R)-3-acetamido-4,5-diacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxypentanoylamino]propylamino]-3-oxopropoxy]methyl]-2-aminopropoxy]propanoylamino]propylamino]-5-oxopentoxy]-3,4-diacetyloxyoxan-2-yl]methyl acetate
|
| Synonyms |
Tri-GalNAc(OAc)3; 1159408-64-6; peracetylated tri-GalNAc-amine; orb2279004; SCHEMBL20154773;
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| HS Tariff Code |
2934.99.9001
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| 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 : ~10 mg/mL (~5.57 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.33 mg/mL (0.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 13.3 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume 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: ≥ 1.33 mg/mL (0.74 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 13.3 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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: ≥ 1.33 mg/mL (0.74 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 | 0.5574 mL | 2.7872 mL | 5.5744 mL | |
| 5 mM | 0.1115 mL | 0.5574 mL | 1.1149 mL | |
| 10 mM | 0.0557 mL | 0.2787 mL | 0.5574 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.
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