| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Not applicable. vc-PABC-DM1 is a drug-linker conjugate for ADC synthesis, not a drug. The vc (valine-citrulline) peptide is a cleavable dipeptide linker that is stable in circulation but is cleaved by cathepsin B inside lysosomes of target cells. The PABC (p-aminobenzylcarbamate) spacer facilitates efficient release of the DM1 payload. DM1 (maytansinoid) is a potent microtubule-targeting agent that inhibits tubulin polymerization. vc-PABC-DM1 can be used to explore serum stability of disulfide linker-based ADC molecules.
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| ln Vitro |
As a research intermediate for ADC synthesis, vc-PABC-DM1 has no direct biological activity. Its value lies in enabling the synthesis of stable and functional ADCs. The resulting ADCs exhibit potent cytotoxicity against target antigen-positive cancer cells with IC50 values in the picomolar to nanomolar range. The linker's stability in serum is a key parameter studied using this compound.
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| ln Vivo |
No specific in vivo data is reported for vc-PABC-DM1 alone. As a drug-linker conjugate, it is conjugated to an antibody to form an ADC. ADCs synthesized with vc-PABC-DM1 have been shown to have excellent serum stability and potent in vivo efficacy in tumor xenograft models. The cleavable valine-citrulline dipeptide is specifically cleaved by lysosomal cathepsin B, ensuring targeted payload release.
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| Enzyme Assay |
vc-PABC-DM1 is used to synthesize disulfide linker-based ADC molecules. For cell-free stability studies, vc-PABC-DM1 is incubated with human or mouse serum (50% serum in PBS) at 37degC for up to 72-120 hours. At defined time points, samples are taken, and the intact drug-linker conjugate is extracted and analyzed by LC-MS. The half-life of the conjugate in serum is calculated from the disappearance curve. To assess cathepsin B cleavage, purified cathepsin B is incubated with vc-PABC-DM1 (1-10 uM) in acetate buffer (pH 5.0) at 37degC for 0-24 hours, and DM1 release is quantified by LC-MS.
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| Cell Assay |
Not applicable. vc-PABC-DM1 is not used directly in cell-based assays. The complete ADC is used for cell culture studies. Target-positive cancer cells (e.g., HER2-positive SK-BR-3 cells) are seeded in 96-well plates (5,000 cells/well) and treated with serial dilutions of the ADC (0.001-100 nM) for 72-96 hours. Cell viability is measured using the CellTiter-Glo assay. Cytotoxicity is compared between target-positive and target-negative cell lines to calculate the selectivity index. In a bystander killing assay, a mixture of target-positive and target-negative cells is treated with the ADC, and target-negative cell death is quantified by flow cytometry.
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| Animal Protocol |
No specific in vivo animal study protocols are documented. For an ADC synthesized with vc-PABC-DM1, a typical protocol involves establishing subcutaneous xenografts of target-positive cancer cells in 6-8 week old female NSG mice. When tumors reach 100-200 mm3, the ADC (e.g., trastuzumab-vc-PABC-DM1) is administered intravenously at a single dose of 1-5 mg/kg (or multiple doses). Tumor volume is measured twice weekly. At study termination, tumors are excised for IHC (Ki67, cleaved caspase-3). Blood is collected for PK analysis (total ADC, intact ADC, and DM1 release).
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| ADME/Pharmacokinetics |
Not applicable for the drug-linker conjugate. The vc-PABC-DM1 conjugate has a molecular weight of 1099.73 g/mol. When conjugated to an antibody, the ADC exhibits PK properties similar to the parent antibody (half-life of several days in mice). The vc linker is stable in circulation (half-life >7 days) but is efficiently cleaved in lysosomes. The DM1 payload is released intracellularly and exhibits a short tissue half-life.
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| Toxicity/Toxicokinetics |
No toxicity data is reported for vc-PABC-DM1. DM1 is a potent microtubule inhibitor with significant cytotoxicity. When conjugated to an antibody, the ADC must be handled as a highly potent cytotoxic compound. Standard ADC safety guidelines should be followed. The compound is for research use only, not for human therapeutic use.
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| References |
[1]. Widdison WC. Novel maytansinoid derivatives with peptide linker and conjugates thereof. WO2012177837A2.
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| Additional Infomation |
vc-PABC-DM1 has the molecular formula C53H75ClN8O13S and a molecular weight of 1099.73. The vc (valine-citrulline) dipeptide is a cathepsin-cleavable linker widely used in FDA-approved ADCs such as brentuximab vedotin (Adcetris®) and polatuzumab vedotin. DM1 is a maytansinoid microtubule inhibitor that binds to tubulin and inhibits polymerization. The compound is stored as a powder at -20degC. It is for research use only.
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| Molecular Formula |
C53H75CLN8O13S
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| CAS # |
1416792-90-9
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| Appearance |
White to off-white solid powder
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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 |
| 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 (~90.93 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.) |
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.
Products are for research use only; We do not sell to patients
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