| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg | |||
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| Targets |
Mc-Val-Cit-PAB-Cl targets the protease cathepsin B, which is overexpressed in the lysosomes of many cancer cells. The Val-Cit dipeptide sequence within the linker is specifically recognized and cleaved by this enzyme, ensuring that the cytotoxic payload is released only after the ADC has been internalized by the target cell. This targeted approach allows for the selective killing of tumor cells while sparing healthy tissues.
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| ln Vitro |
As a linker, Mc-Val-Cit-PAB-Cl itself does not possess direct biological activity. Its activity is demonstrated through the efficacy of the resulting ADC. For instance, when used to conjugate the potent toxin monomethyl auristatin E (MMAE) to an anti-CD22 antibody, the resulting ADC, anti-CD22-MC-VC-PABC-MMAE, exhibited potent cytotoxicity against BJAB and WSU cell lines with IC50 values of 3.3 nM and 0.95 nM, respectively. This demonstrates the linker's ability to effectively deliver its payload to target cells.
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| ln Vivo |
In vivo, the activity of Mc-Val-Cit-PAB-Cl is observed as the antitumor efficacy of the ADCs it helps create. While the linker itself is not administered as a drug, the ADCs constructed with it have shown significant tumor growth inhibition in xenograft models. The Val-Cit-PAB system is known for its stability in circulation, preventing premature drug release, and its efficient cleavage in the tumor microenvironment, leading to high local concentrations of the cytotoxic agent.
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| Enzyme Assay |
The enzymatic cleavage of Mc-Val-Cit-PAB-Cl is typically evaluated using recombinant cathepsin B in a cell-free assay. The linker is incubated with the enzyme, and the release of the PAB-payload moiety is monitored, often by HPLC or LC-MS. The efficiency of cleavage is determined by measuring the rate of product formation, confirming the linker's susceptibility to the target protease.
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| Cell Assay |
Cellular assays are performed using cancer cell lines that express the target antigen. Cells are treated with the complete ADC (antibody-linker-payload), and cell viability is assessed after several days using standard assays such as CellTiter-Glo or MTT. The IC50 value, representing the concentration of ADC required to inhibit cell growth by 50%, is calculated to quantify the potency of the ADC construct.
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| Animal Protocol |
In vivo efficacy is evaluated in mouse xenograft models. Mice bearing established tumors are administered the ADC (containing the Mc-Val-Cit-PAB-Cl linker) via intravenous injection. Tumor volume is measured regularly, and the antitumor activity is assessed by comparing tumor growth in treated groups to that in control groups. Parameters such as tumor growth inhibition (TGI) and regression are used to quantify efficacy.
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| ADME/Pharmacokinetics |
Mc-Val-Cit-PAB-Cl has a molecular weight of 591.10 g/mol and a chemical formula of C28H39ClN6O6. As a synthetic linker, its pharmacokinetic properties are primarily relevant when incorporated into an ADC. The Val-Cit-PAB system is designed to be stable in plasma, exhibiting a long half-life, which ensures that the cytotoxic payload is not released prematurely into the bloodstream.
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| Toxicity/Toxicokinetics |
Mc-Val-Cit-PAB-Cl is not intended as a therapeutic agent itself and is used as a research tool. Its safety and toxicity are assessed as part of the overall ADC construct. The Val-Cit-PAB linker is generally well-tolerated, and the primary toxicity is associated with the released payload. The design aims to maximize the therapeutic index by limiting payload exposure to healthy tissues.
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| Additional Infomation |
Mc-Val-Cit-PAB-Cl is a key component in the development of next-generation ADCs. It is a maleimide caproyl-valine-citrulline-p-aminobenzyl chloride linker. Its ability to be cleaved by cathepsin B, a protease abundant in the tumor microenvironment, makes it a versatile tool for creating targeted cancer therapies. This linker is central to the mechanism of action of several clinically relevant ADCs, which rely on it for the targeted delivery and release of their potent payloads.
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| Molecular Formula |
C28H39CLN6O6
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|---|---|
| Molecular Weight |
591.0989
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| Exact Mass |
590.261
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| CAS # |
1639351-92-0
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| PubChem CID |
117719308
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| Appearance |
White to off-white solid powder
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| LogP |
1.3
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
17
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| Heavy Atom Count |
41
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| Complexity |
948
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC(C)[C@@H](C(=O)N[C@@H](CCCNC(=O)N)C(=O)NC1=CC=C(C=C1)CCl)NC(=O)CCCCCN2C(=O)C=CC2=O
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| InChi Key |
TUMQZNBKSWFFAZ-OFVILXPXSA-N
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| InChi Code |
InChI=1S/C28H39ClN6O6/c1-18(2)25(34-22(36)8-4-3-5-16-35-23(37)13-14-24(35)38)27(40)33-21(7-6-15-31-28(30)41)26(39)32-20-11-9-19(17-29)10-12-20/h9-14,18,21,25H,3-8,15-17H2,1-2H3,(H,32,39)(H,33,40)(H,34,36)(H3,30,31,41)/t21-,25-/m0/s1
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| Chemical Name |
N-[(2S)-1-[[(2S)-5-(carbamoylamino)-1-[4-(chloromethyl)anilino]-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-6-(2,5-dioxopyrrol-1-yl)hexanamide
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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) |
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 | 1.6918 mL | 8.4588 mL | 16.9176 mL | |
| 5 mM | 0.3384 mL | 1.6918 mL | 3.3835 mL | |
| 10 mM | 0.1692 mL | 0.8459 mL | 1.6918 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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