| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
The target of DBCO-Val-Cit-PABC-PNP is cathepsin B and the azide group in the SPAAC reaction. The Val-Cit dipeptide is specifically cleaved by lysosomal cathepsin B, which is overexpressed in many tumor cells. The PABC spacer undergoes self-immolation upon cleavage, releasing the free payload. The DBCO group enables copper-free click chemistry conjugation to azide-containing antibodies. The PNP ester reacts with amines.
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| ln Vitro |
ADCs are made up of an antibody and an ADC cytotoxin that are joined together by an ADC linker[1].
In vitro activity of DBCO-Val-Cit-PABC-PNP is evaluated for its cleavage efficiency by recombinant cathepsin B. The linker is incubated with the enzyme in a cleavage buffer containing DTT, and the release of the payload is monitored by HPLC or LC-MS. The reaction kinetics and specificity are assessed to confirm that cleavage occurs selectively at the Val-Cit site. |
| ln Vivo |
In vivo activity of ADCs containing DBCO-Val-Cit-PABC-PNP is assessed in animal models. The linker's stability in circulation and selective cleavage within tumor cells are critical for achieving a favorable therapeutic index. In vivo studies typically involve administering the ADC to tumor-bearing mice and monitoring tumor growth inhibition, body weight, and survival.
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| Enzyme Assay |
For non-cellular enzyme assays, DBCO-Val-Cit-PABC-PNP is incubated with cathepsin B in a buffer containing 5 mM DTT at 37°C. The reaction is quenched at various time points, and the extent of cleavage is analyzed by reverse-phase HPLC. The assay is used to determine the cleavage rate and to confirm that the linker is stable in the absence of the enzyme.
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| Cell Assay |
In vitro cell experiments with DBCO-Val-Cit-PABC-PNP typically involve conjugating the linker to a payload and an antibody, then testing the resulting ADC in cancer cell lines. Cells are incubated with the ADC, and internalization is monitored. After internalization, the linker is cleaved by lysosomal cathepsin B, releasing the cytotoxic payload. Cell viability is measured.
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| Animal Protocol |
In vivo animal experiments with ADCs containing DBCO-Val-Cit-PABC-PNP typically use tumor-bearing mice. The ADC is administered intravenously, and tumor volume is measured regularly. The linker's ability to release the payload selectively in the tumor microenvironment is assessed by analyzing tumor tissue for free drug. Pharmacokinetic and toxicological parameters are evaluated.
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| References |
| Molecular Formula |
C??H??N?O??
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|---|---|
| Molecular Weight |
859.92
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| Appearance |
White to off-white solid powder
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| SMILES |
CC([C@@H](C(N[C@H](C(NC1=CC=C(C=C1)COC(OC2=CC=C(C=C2)[N+]([O-])=O)=O)=O)CCCNC(N)=O)=O)NC(CCCCC(N3CC4=C(C#CC5=C3C=CC=C5)C=CC=C4)=O)=O)C
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| Synonyms |
DBCOValCitPABCPNP; DBCO Val Cit PABC PNP
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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, 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: ~100 mg/mL (~116.3 mM; with ultrasonication)
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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 | 1.1629 mL | 5.8145 mL | 11.6290 mL | |
| 5 mM | 0.2326 mL | 1.1629 mL | 2.3258 mL | |
| 10 mM | 0.1163 mL | 0.5814 mL | 1.1629 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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