| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 500mg | |||
| Other Sizes |
| Targets |
The primary target of MAC glucuronide linker-1 is the tumor microenvironment, specifically the enzyme β-glucuronidase which is overexpressed in various cancer tissues. As an ADC linker, it does not have a direct pharmacological target but serves as a substrate for enzymatic cleavage. The linker is designed to be stable in circulation while being selectively cleaved by β-glucuronidase within the tumor microenvironment, enabling targeted release of the conjugated cytotoxic drug. This targeting strategy improves the therapeutic index of ADC therapies by concentrating drug delivery to tumor sites.
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| ln Vitro |
In vitro activity of MAC glucuronide linker-1 is evaluated through cleavage assays using recombinant β-glucuronidase or cell lysates from cancer cells that overexpress the enzyme. The linker demonstrates efficient cleavage in the presence of β-glucuronidase, releasing the attached cytotoxic payload. Stability studies in plasma and serum show that the linker remains intact in circulation, preventing premature drug release. The PEG units in the linker improve solubility and reduce aggregation of ADC constructs. These properties make MAC glucuronide linker-1 a valuable tool for developing targeted cancer therapies.
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| ln Vivo |
In vivo activity of MAC glucuronide linker-1 is assessed in tumor-bearing mouse models where ADCs constructed with this linker demonstrate enhanced antitumor efficacy compared to non-cleavable linkers. The linker enables selective drug release within the tumor microenvironment, resulting in improved tumor growth inhibition and reduced systemic toxicity. Pharmacodynamic studies show that the linker-mediated drug release correlates with β-glucuronidase expression levels in tumors. The PEG units contribute to favorable pharmacokinetic properties by extending circulation half-life and improving drug accumulation in tumor tissues.
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| Enzyme Assay |
The cell-free assay for MAC glucuronide linker-1 involves incubating the linker-drug conjugate with purified β-glucuronidase enzyme or tumor tissue homogenates. The reaction is typically carried out in buffered solutions at physiological pH (7.4) and 37°C. Cleavage efficiency is monitored by HPLC or LC-MS to quantify the release of the cytotoxic payload from the linker. Kinetic parameters such as Vmax and Km are determined by measuring the rate of drug release at various substrate concentrations. Stability assays are performed in human plasma and serum to evaluate the linker's resistance to non-specific cleavage.
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| Cell Assay |
Cellular assays for MAC glucuronide linker-1 involve treating cancer cell lines that express varying levels of β-glucuronidase with ADC constructs containing the linker. Cells are incubated with the ADC for 24-72 hours, and cell viability is assessed using standard assays such as MTT, CellTiter-Glo, or flow cytometry. The potency of the ADC is correlated with β-glucuronidase expression levels in the target cells. Specificity is evaluated by comparing cytotoxicity in β-glucuronidase-positive versus negative cell lines. Internalization and intracellular trafficking of the ADC are studied using fluorescently labeled antibodies and confocal microscopy.
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| Animal Protocol |
In vivo animal studies for MAC glucuronide linker-1 are conducted in xenograft mouse models bearing human tumor cell lines. ADCs constructed with this linker are administered intravenously at various doses, typically ranging from 1-10 mg/kg. Tumor growth inhibition is monitored by measuring tumor volume using calipers twice weekly. Pharmacokinetic parameters including half-life, Cmax, and AUC are determined from plasma samples collected at various time points. Biodistribution studies assess the accumulation of the ADC and released drug in tumor and normal tissues. Efficacy is evaluated by comparing tumor growth rates and survival between treatment and control groups.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of MAC glucuronide linker-1 include a molecular weight of 897.9 g/mol and molecular formula C42H47N3O17S. The compound has a predicted density of 1.43 g/cm3 and is soluble in DMSO (80 mg/mL, 89.1 mM). As an ADC linker, its PK properties are typically evaluated when conjugated to antibodies and cytotoxic payloads. The PEG units contribute to improved aqueous solubility and reduced immunogenicity. Storage recommendations include keeping away from moisture, with powder stable at -20°C for up to 3 years and in solvent at -80°C for 1 year.
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| Toxicity/Toxicokinetics |
Toxicity of MAC glucuronide linker-1 is primarily evaluated as part of the complete ADC construct rather than as a standalone compound. The linker itself is designed to be non-toxic, with toxicity arising from the released cytotoxic payload. Preclinical safety studies of ADCs containing this linker typically include acute and repeat-dose toxicity assessments in rodent and non-rodent species. The glucuronide-based cleavage mechanism is intended to reduce systemic toxicity by limiting drug release to the tumor microenvironment. Standard safety precautions should be followed when handling this compound, including the use of personal protective equipment.
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| Additional Infomation |
MAC glucuronide linker-1 is a cleavable ADC linker containing three PEG units, used for constructing antibody-drug conjugates with improved therapeutic efficacy and selectivity. Its mechanism involves enzymatic cleavage by β-glucuronidase, an enzyme overexpressed in tumor microenvironments, enabling targeted drug release. The linker enhances ADC properties by improving solubility, reducing aggregation, and enabling selective payload delivery. This compound is a research tool for developing targeted cancer therapies and has not entered clinical trials as a standalone agent. MAC glucuronide linker-1 is strictly for research purposes and not for therapeutic use in humans.
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| Molecular Formula |
C42H47N3O17S
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|---|---|
| Molecular Weight |
897.897491693497
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| Exact Mass |
897.262
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| CAS # |
2222981-71-5
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| PubChem CID |
142754568
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| Appearance |
White to off-white solid powder
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| LogP |
2.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
17
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| Rotatable Bond Count |
22
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| Heavy Atom Count |
63
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| Complexity |
1740
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| Defined Atom Stereocenter Count |
5
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| SMILES |
S(C)(CCNC(=O)OCC1=CC=C(C(=C1)NC(CN(C)C(=O)OCC1C2C=CC=CC=2C2=CC=CC=C12)=O)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](C(=O)OC)O1)OC(C)=O)OC(C)=O)OC(C)=O)(=O)=O
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| InChi Key |
HKCMXFVQNGHVML-KWMSUFDQSA-N
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| InChi Code |
InChI=1S/C42H47N3O17S/c1-23(46)58-35-36(59-24(2)47)38(60-25(3)48)40(62-37(35)39(50)55-5)61-33-16-15-26(21-56-41(51)43-17-18-63(6,53)54)19-32(33)44-34(49)20-45(4)42(52)57-22-31-29-13-9-7-11-27(29)28-12-8-10-14-30(28)31/h7-16,19,31,35-38,40H,17-18,20-22H2,1-6H3,(H,43,51)(H,44,49)/t35-,36-,37-,38+,40+/m0/s1
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| Chemical Name |
methyl (2S,3S,4S,5R,6S)-3,4,5-triacetyloxy-6-[2-[[2-[9H-fluoren-9-ylmethoxycarbonyl(methyl)amino]acetyl]amino]-4-(2-methylsulfonylethylcarbamoyloxymethyl)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 (~222.74 mM)
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| 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 | 1.1137 mL | 5.5685 mL | 11.1371 mL | |
| 5 mM | 0.2227 mL | 1.1137 mL | 2.2274 mL | |
| 10 mM | 0.1114 mL | 0.5569 mL | 1.1137 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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