| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
The target of the entire ADC construct is determined by the antibody to which Val‑Cit‑amide‑Ph‑Maytansine is attached. Maytansine itself targets tubulin, binding at the same site as the vinca alkaloids. When released inside cancer cells, maytansine inhibits microtubule polymerization, leading to G2/M cell cycle arrest and apoptosis.
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|---|---|
| ln Vitro |
The conjugate has no inherent in vitro activity without its antibody. However, the free maytansine payload (released after Val‑Cit cleavage) potently inhibits the proliferation of various cancer cell lines in vitro, typically with IC50 values in the low nanomolar to picomolar range (e.g., 0.1‑1 nM for HER2‑positive cell lines). The Val‑Cit linker itself is stable in circulation but is effectively cleaved in lysosomes.
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| ln Vivo |
In a mouse xenograft model, an ADC constructed with an anti‑c‑Met antibody conjugated to Val‑Cit‑amide‑Ph‑Maytansine produces dose‑dependent tumor regression. For example, in a gastric cancer xenograft model, a single intravenous dose of the ADC (3‑10 mg/kg) leads to durable tumor shrinkage and, in some studies, complete tumor eradication. The in vivo efficacy is much higher than that of the non‑targeted maytansine, which causes systemic toxicity.
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| Enzyme Assay |
A cathepsin B cleavage assay is performed to evaluate the Val‑Cit linker. The conjugate (10 uM) is incubated with recombinant human cathepsin B (10 nM) in acetate buffer (pH 5.5, 100 mM NaCl, 1 mM EDTA, 1 mM DTT) for 1‑4 hours at 37degC. The released maytansine is quantified by LC‑MS/MS and compared to a control incubation without enzyme. The linker is considered cleavable if more than 80% of maytansine is released within 2 hours.
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| Cell Assay |
Cancer cells expressing the target antigen (e.g., c‑Met or HER2) are seeded in 96‑well plates and treated with the intact ADC (0.01‑100 nM) for 72‑96 hours. Cell viability is measured by the CellTiter‑Glo assay. To confirm that the Val‑Cit linker is responsible for intracellular release, cells are pre‑treated with the lysosomal protease inhibitor E‑64d (10 uM) for 2 hours before adding the ADC; this should block the cytotoxicity.
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| Animal Protocol |
A mouse xenograft model is established by subcutaneous injection of 5×10⁶ tumor cells (e.g., MKN‑45 gastric cancer or NCI‑N87 gastric cancer cells) into BALB/c nude mice. When tumors reach 100‑200 mm3, the ADC (typically 1‑10 mg/kg) is administered intravenously once a week for 2‑4 weeks. Tumor volumes are measured twice weekly with calipers, and body weight is monitored as an indicator of toxicity. At the end of the study, tumors are excised and analyzed for mitotic index and apoptosis.
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| ADME/Pharmacokinetics |
The conjugate itself has a high molecular weight (usually >1500 Da for the linker‑payload alone, and >150 kDa for the whole ADC). Following intravenous administration, ADCs remain in the circulation for days to weeks, with terminal half‑lives of 2‑5 days in humans. The Val‑Cit‑amide‑Ph‑Maytansine conjugate is stable in plasma and is cleared primarily by catabolism of the antibody after target‑mediated uptake or by non‑specific uptake into the reticuloendothelial system.
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| Toxicity/Toxicokinetics |
The major toxicity of maytansine‑based ADCs is on‑target/off‑tumor toxicity (if the target antigen is expressed in normal tissues) and off‑target microtubule‑mediated toxicity (peripheral neuropathy, neutropenia). The Val‑Cit linker is designed to minimize premature release, reducing systemic exposure to free maytansine. However, in animal studies, high doses (≥20 mg/kg) of the ADC can still cause weight loss, thrombocytopenia, and liver enzyme elevations.
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| References | |
| Additional Infomation |
Val‑Cit‑amide‑Ph‑Maytansine is an advanced ADC research tool. The Val‑Cit dipeptide combined with a PAB spacer is one of the most widely used cleavable linker technologies, as seen in FDA‑approved ADCs such as brentuximab vedotin (which uses a Val‑Cit linker with monomethyl auristatin E). This particular conjugate is being explored for c‑Met‑targeted therapy. It is not an approved drug and is for research use only.
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| Molecular Formula |
C51H71CLN8O14
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|---|---|
| Molecular Weight |
1055.61
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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 (~94.73 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.37 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.37 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (2.37 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9473 mL | 4.7366 mL | 9.4732 mL | |
| 5 mM | 0.1895 mL | 0.9473 mL | 1.8946 mL | |
| 10 mM | 0.0947 mL | 0.4737 mL | 0.9473 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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