| Size | Price | Stock | Qty |
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| 100mg |
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| 500mg |
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| 1g |
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| Other Sizes |
| Targets |
Cleavable Linker Glycosidase Cleavable Linker
MAC glucuronide linker-2 targets the tumor microenvironment through its enzyme-cleavable mechanism. The glucuronide moiety is specifically cleaved by β-glucuronidase, an enzyme that is overexpressed in the tumor microenvironment. This enables selective drug release within tumor tissues, enhancing the therapeutic index and stability of antibody-drug conjugates. As an ADC linker, it enables the conjugation of cytotoxic payloads to antibodies, facilitating selective delivery of drugs to cancer cells. The enzyme-cleavable nature provides controlled drug release. |
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| ln Vitro |
In vitro activity of MAC glucuronide linker-2 is assessed by its ability to form stable conjugates with antibodies and its selective cleavage by β-glucuronidase. The efficiency of conjugation to antibodies is evaluated by SDS-PAGE, mass spectrometry, and HPLC. The cleavable nature of the glucuronide moiety is confirmed by incubation with β-glucuronidase, followed by analysis of conjugate stability and drug release by HPLC or LC-MS. Cell binding and internalization studies are conducted using target-positive and target-negative cell lines to assess specificity and intracellular drug release.
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| ln Vivo |
In vivo studies for MAC glucuronide linker-2 are typically conducted as part of complete ADC development. The ADC is evaluated in mouse xenograft models bearing target-positive tumors. Efficacy is assessed by tumor growth inhibition, and pharmacokinetic studies evaluate the stability of the linker in circulation. The enzyme-cleavable nature of the glucuronide moiety is designed to enable selective drug release in the tumor microenvironment where β-glucuronidase is overexpressed. This selective release mechanism enhances therapeutic index and reduces systemic toxicity.
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| Enzyme Assay |
For conjugation assays, MAC glucuronide linker-2 is dissolved in anhydrous DMSO or DMF and added to a solution of antibody or targeting protein in PBS buffer. The reaction is incubated at room temperature for 2-4 hours, and the extent of conjugation is monitored by SDS-PAGE or MALDI-TOF mass spectrometry. For enzyme cleavage studies, the conjugate is incubated with β-glucuronidase at 37°C, and the release of payload is analyzed by HPLC or LC-MS. The stability of the conjugate in plasma is assessed by incubation in mouse or human plasma at 37°C. Purity is min. 95.0% by HPLC and qNMR.
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| Cell Assay |
Target-positive cancer cell lines are cultured in appropriate media. Cells are treated with MAC glucuronide linker-2-containing ADC conjugates at various concentrations for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays, and IC50 values are calculated. Cell binding is evaluated by flow cytometry using fluorescently labeled conjugates, and internalization is assessed using confocal microscopy or pH-sensitive dyes. For enzyme-dependent activity, cells are co-treated with β-glucuronidase inhibitors or modulators to confirm the cleavage mechanism.
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| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice bearing target-positive tumor xenografts are administered the complete ADC (containing MAC glucuronide linker-2) via intravenous injection. Dosing typically involves multiple injections at 1-2 week intervals. Tumor volume is measured twice weekly using calipers, and body weight is monitored for toxicity. At study termination, tumors and major organs are collected for histopathological analysis and drug concentration measurement. Pharmacokinetic studies assess ADC stability and drug release in circulation.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of MAC glucuronide linker-2 are characterized as part of the complete ADC. The glucuronide moiety provides hydrophilicity that can improve the pharmacokinetic profile of the ADC. The enzyme-cleavable linker enables selective drug release in the tumor microenvironment. The compound has a melting point of 138.0-142.0°C. Detailed PK parameters such as half-life, clearance, and volume of distribution depend on the specific antibody and payload used in the conjugate. Storage at 2-8°C is recommended.
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| Toxicity/Toxicokinetics |
MAC glucuronide linker-2 is a chemical reagent intended for research use only and is not approved for human therapeutic use. As an enzyme-cleavable ADC linker, it enables selective drug release in the tumor microenvironment through cleavage by β-glucuronidase. The linker enhances the therapeutic index and stability of antibody-drug conjugates. Standard laboratory safety precautions should be followed when handling this compound. Purity is min. 95.0% by HPLC and qNMR. Storage at 2-8°C is recommended.
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| References | |
| Additional Infomation |
MAC glucuronide linker-2 is an enzyme-cleavable ADC linker with molecular formula C20H25NO11 and molecular weight 455.41. It incorporates a glucuronide moiety cleaved by β-glucuronidase in the tumor microenvironment. The linker is used in the synthesis of antibody-drug conjugates for targeted cancer therapy. It is for research use only and has not been approved for clinical applications. Purity is min. 95.0% by HPLC and qNMR; melting point 138.0-142.0°C. Storage at 2-8°C is recommended.
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| Molecular Formula |
C20H25NO11
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|---|---|
| Molecular Weight |
455.412606954575
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| Exact Mass |
455.142
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| CAS # |
229977-57-5
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| PubChem CID |
59816530
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| Appearance |
White to yellow solid powder
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| LogP |
-0.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
32
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| Complexity |
699
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| Defined Atom Stereocenter Count |
5
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| SMILES |
NC1C(O[C@@H]2O[C@H](C(=O)OC)[C@@H](OC(=O)C)[C@H](OC(=O)C)[C@H]2OC(=O)C)=CC=C(CO)C=1
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| InChi Key |
ZAZPQJAJSIUIEY-KVIJGQROSA-N
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| InChi Code |
InChI=1S/C20H25NO11/c1-9(23)28-15-16(29-10(2)24)18(30-11(3)25)20(32-17(15)19(26)27-4)31-14-6-5-12(8-22)7-13(14)21/h5-7,15-18,20,22H,8,21H2,1-4H3/t15-,16-,17-,18+,20+/m0/s1
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| Chemical Name |
methyl (2S,3S,4S,5R,6S)-3,4,5-triacetyloxy-6-[2-amino-4-(hydroxymethyl)phenoxy]oxane-2-carboxylate
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : 200 mg/mL (439.16 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (10.98 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 50.0 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: ≥ 5 mg/mL (10.98 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 50.0 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: ≥ 5 mg/mL (10.98 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 | 2.1958 mL | 10.9791 mL | 21.9582 mL | |
| 5 mM | 0.4392 mL | 2.1958 mL | 4.3916 mL | |
| 10 mM | 0.2196 mL | 1.0979 mL | 2.1958 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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