| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
The compound does not have a single target. Its targeting is defined by the antibody it is conjugated to. The payload, MMAE, is a potent inhibitor of tubulin polymerization, leading to mitotic arrest and apoptosis in targeted cells. The TCO-PEG4-VC-PA linker is designed for stability in circulation and cleavable (by cathepsin B) within the target cancer cell's lysosomes.
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| ln Vitro |
An ADC cytotoxin is connected to an antibody by use of an ADC linker to form an ADC.
The biological activity is mediated by the release of MMAE. The linker-payload construct itself is not directly tested for activity in vitro. Instead, the activity of the final ADC is evaluated. The payload, MMAE, is a well-characterized tubulin inhibitor, causing G2/M cell cycle arrest and apoptosis at low nanomolar concentrations in sensitive cancer cell lines. |
| ln Vivo |
The in vivo activity is determined entirely by the targeting antibody conjugated to this linker-payload. For example, an anti-HER2 ADC built with this linker would show in vivo efficacy in HER2-positive xenograft models. The linker is designed to be stable in circulation (reducing systemic toxicity) and release MMAE efficiently once the ADC is internalized into the target cell.
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| Enzyme Assay |
A biochemical binding assay is not applicable for the full ADC. For the linker alone, the TCO group is evaluated via a click chemistry reaction with a tetrazine-labeled molecule. The reaction kinetics can be monitored by UV-Vis spectroscopy or HPLC. The cleavage of the VC-PAB linker by cathepsin B can be tested in vitro: the linker-payload is incubated with recombinant cathepsin B, and the release of MMAE is quantified by LC-MS.
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| Cell Assay |
The in vitro activity is measured using cell viability assays. The final ADC is added to antigen-positive target cancer cells (e.g., HER2+ cells for a HER2-ADC) and antigen-negative control cells. After 72-120 hours of exposure, cell viability is measured by CellTiter-Glo. For bystander effect studies, a mixture of antigen-positive and antigen-negative cells is used. The release of free MMAE by the cleavable linker allows for killing of neighboring antigen-negative cells, which is an advantage of this linker design.
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| Animal Protocol |
In vivo animal experimental procedures depend on the specific antibody conjugated to this linker-payload. A typical protocol for a TCO-PEG4-VC-PAB-MMAE ADC involves: 1. Conjugation of the drug-linker to a tetrazine-modified antibody via iEDDA click chemistry. 2. In vivo efficacy in a mouse xenograft model: Nude mice are injected subcutaneously with antigen-positive tumor cells (e.g., HER2+ cells). When tumors reach ~150 mm3, mice are treated with the ADC (intravenous, e.g., 3-10 mg/kg) once weekly for 2-3 weeks. Tumor volume is measured twice weekly to assess tumor growth delay.
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| ADME/Pharmacokinetics |
Not applicable for the linker-payload alone. The pharmacokinetic properties of the final ADC are determined by the characteristics of the antibody component. The linker is designed to be stable in plasma (to prevent premature MMAE release) but cleavable inside the cell. The half-life of the ADC is typically measured by an ELISA that detects the intact conjugate in mouse serum samples.
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| Toxicity/Toxicokinetics |
Not applicable for the linker-payload alone. The toxicological profile is determined by the final ADC construct. The linker is designed to improve the therapeutic window by providing stability in circulation, which reduces off-target toxicity from payload release. The primary toxicities are typically on-target, off-tumor effects, or general toxicity related to the payload's mechanism.
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| References | |
| Additional Infomation |
TCO-PEG4-VC-PAB-MMAE is a research-grade chemical for ADC development. The use of TCO-tetrazine iEDDA click chemistry allows for site-specific conjugation of the drug to the antibody, which leads to a more homogeneous ADC product with a defined drug-to-antibody ratio (DAR). As of the latest updates, it is a pre-clinical reagent and has not been approved for medical use.
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| Molecular Formula |
C78H127N11O19
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|---|---|
| Molecular Weight |
1522.90530228615
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| Exact Mass |
1521.93
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| CAS # |
2758671-45-1
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| PubChem CID |
165412587
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| Appearance |
White to off-white solid powder
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| LogP |
6
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| Hydrogen Bond Donor Count |
9
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| Hydrogen Bond Acceptor Count |
19
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| Rotatable Bond Count |
50
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| Heavy Atom Count |
108
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| Complexity |
2740
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| Defined Atom Stereocenter Count |
12
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| SMILES |
O(C)[C@H]([C@H](C(N[C@H](C)[C@H](C1C=CC=CC=1)O)=O)C)[C@@H]1CCCN1C(C[C@H]([C@H]([C@@H](C)CC)N(C)C([C@H](C(C)C)NC([C@H](C(C)C)N(C(=O)OCC1C=CC(=CC=1)NC([C@H](CCCNC(N)=O)NC([C@H](C(C)C)NC(CCOCCOCCOCCOCCNC(=O)OC1CCC=CCCC1)=O)=O)=O)C)=O)=O)OC)=O |c:97|
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| InChi Key |
RCUWIJNSWOFTSK-CYFMCQSESA-N
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| InChi Code |
InChI=1S/C78H127N11O19/c1-15-53(8)68(62(101-13)48-64(91)89-39-25-31-61(89)70(102-14)54(9)71(93)82-55(10)69(92)57-26-20-19-21-27-57)87(11)75(97)66(51(4)5)86-74(96)67(52(6)7)88(12)78(100)107-49-56-32-34-58(35-33-56)83-72(94)60(30-24-37-80-76(79)98)84-73(95)65(50(2)3)85-63(90)36-40-103-42-44-105-46-47-106-45-43-104-41-38-81-77(99)108-59-28-22-17-16-18-23-29-59/h16-17,19-21,26-27,32-35,50-55,59-62,65-70,92H,15,18,22-25,28-31,36-49H2,1-14H3,(H,81,99)(H,82,93)(H,83,94)(H,84,95)(H,85,90)(H,86,96)(H3,79,80,98)/b17-16+/t53-,54+,55+,59?,60-,61-,62+,65-,66-,67-,68-,69+,70+/m0/s1
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| Chemical Name |
[4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[3-[2-[2-[2-[2-[[(4E)-cyclooct-4-en-1-yl]oxycarbonylamino]ethoxy]ethoxy]ethoxy]ethoxy]propanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl N-[(2S)-1-[[(2S)-1-[[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylcarbamate
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
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
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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 | 0.6566 mL | 3.2832 mL | 6.5664 mL | |
| 5 mM | 0.1313 mL | 0.6566 mL | 1.3133 mL | |
| 10 mM | 0.0657 mL | 0.3283 mL | 0.6566 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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