| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 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.
|
|---|---|
| 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.
|
| Molecular Formula |
C81H129F3N10O38
|
|---|---|
| Molecular Weight |
1907.93
|
| Exact Mass |
1906.842
|
| Elemental Analysis |
C, 50.99; H, 6.82; F, 2.99; N, 7.34; O, 31.86
|
| CAS # |
1159408-65-7
|
| Related CAS # |
1159408-64-6
|
| PubChem CID |
162394061
|
| Appearance |
White to off-white ointment
|
| Hydrogen Bond Donor Count |
11
|
| Hydrogen Bond Acceptor Count |
42
|
| Rotatable Bond Count |
69
|
| Heavy Atom Count |
132
|
| Complexity |
3220
|
| Defined Atom Stereocenter Count |
15
|
| SMILES |
CC(=O)N[C@@H]1[C@H]([C@H]([C@H](O[C@H]1OCCCCC(=O)NCCCNC(=O)CCOCC(COCCC(=O)NCCCNC(=O)CCCCO[C@H]2[C@@H]([C@H]([C@H]([C@H](O2)COC(=O)C)OC(=O)C)OC(=O)C)NC(=O)C)(COCCC(=O)NCCCNC(=O)CCCCO[C@H]3[C@@H]([C@H]([C@H]([C@H](O3)COC(=O)C)OC(=O)C)OC(=O)C)NC(=O)C)N)COC(=O)C)OC(=O)C)OC(=O)C.C(=O)(C(F)(F)F)O
|
| InChi Key |
ZQQFLUVDYMPTBZ-QBHSIBJISA-N
|
| InChi Code |
InChI=1S/C79H128N10O36.C2HF3O2/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;3-2(4,5)1(6)7/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);(H,6,7)/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;2,2,2-trifluoroacetic acid
|
| Synonyms |
Tri-GalNAc(OAc)3 TFA; 1159408-65-7; Tri-GalNAc(OAc)3 (TFA); orb2279003
|
| 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.5241 mL | 2.6206 mL | 5.2413 mL | |
| 5 mM | 0.1048 mL | 0.5241 mL | 1.0483 mL | |
| 10 mM | 0.0524 mL | 0.2621 mL | 0.5241 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
