| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Mal-Val-Lys-PAB-MMAE TFA does not have a receptor target itself; its targeting ability comes from the monoclonal antibody it is conjugated to in an ADC. The mechanistic target of its payload, MMAE, is tubulin. Once the conjugate is internalized into a target cell and the linker is cleaved by lysosomal proteases (cathepsin B), the free MMAE is released. MMAE then exerts its effect by binding to tubulin, inhibiting its polymerization into microtubules. This disruption of the cytoskeleton leads to potent G2/M cell cycle arrest and subsequent apoptotic cell death.
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| ln Vitro |
As a linker-payload conjugate, the molecule itself is not active in standard cell-free assays (e.g., tubulin polymerization assay) due to its size. Its primary in vitro activity is determined only after it is conjugated to an antibody and tested on antigen-positive cells. In such assays, the ADC demonstrates potent and specific cytotoxicity with IC50 values typically in the low nanomolar to picomolar range. The maleimide group allows for site-specific conjugation to thiols. In a cytotoxicity assay, the linker-payload is inactive, confirming it requires antibody-mediated delivery to exert its effect.
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| ln Vivo |
The in vivo activity of Mal-Val-Lys-PAB-MMAE is not directly tested. Instead, it is conjugated to a tumor-targeting antibody to form a functional ADC. When such an ADC is administered in a xenograft mouse model, it exhibits potent anti-tumor activity, often leading to complete and durable tumor regressions. The ADC acts by being internalized via the antibody-antigen interaction, releasing MMAE within the tumor cells. For its use as a reference standard, it is a non-toxic building block until incorporated into a functional ADC.
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| Enzyme Assay |
General in vitro cytostatic activity assay: The linker-payload is typically conjugated to an antibody first. For the conjugate, antigen-positive cancer cells (e.g., 5,000 cells/well) are plated in a 96-well plate. The ADC is added in a dilution series (0.001-10 ug/mL). After 72-96 hours, cell viability is measured using a luminescent CellTiter-Glo® assay. The IC50 is calculated. For the free linker-payload (Mal-Val-Lys-PAB-MMAE TFA), it will not enter cells effectively and is generally non-toxic to cancer cells (IC50 > 10 uM).
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| Cell Assay |
General in vitro linker stability assay: The stability of the linker-payload can be assessed in a cysteine-rich medium. Mal-Val-Lys-PAB-MMAE TFA is incubated in buffer containing 10 mM glutathione (GSH) at 37degC for 24 hours. The reaction mixture is analyzed by LC-MS to monitor the formation of the MMAE drug after GSH-induced cleavage. This validates the redox-sensitivity of the payload release mechanism. For a Caco-2 permeability assay, the linker-payload would have very low permeability (Papp < 1×10-⁶ cm/s).
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| Animal Protocol |
General in vivo animal protocol for ADC efficacy: The linker-payload is conjugated to an antibody. Nude mice bearing xenografts (e.g., 100-200 mm3) are treated with the ADC (0, 1, 3, 10 mg/kg, i.v.) once weekly for 2-3 weeks. Tumor volume is measured twice weekly. The treatment will show dose-dependent tumor growth inhibition (TGI) and potentially tumor regressions. For toxicology, a 28-day study in rats with the final ADC is required for safety assessment.
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| ADME/Pharmacokinetics |
Mal-Val-Lys-PAB-MMAE TFA itself (MW 1215.46 g/mol) is a large, highly polar prodrug. It is not orally bioavailable. If injected intravenously (as an ADC), the conjugate would have a long circulation half-life. However, the free linker-payload would be rapidly cleared by the liver and kidneys. It is designed to be stable in plasma but cleaved within lysosomes. For its use as a quality control standard, its PK is not characterized.
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| Toxicity/Toxicokinetics |
Mal-Val-Lys-PAB-MMAE TFA is used as a building block and is not a drug itself. The final ADC would be evaluated for toxicity, which typically includes bone marrow suppression (neutropenia, thrombocytopenia) and peripheral neuropathy due to the MMAE payload. The linker-payload alone is expected to be non-toxic in vivo as it cannot efficiently enter cells. For impurity qualification, it is not a genotoxic impurity and is handled as a standard hazardous chemical.
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| References | |
| Additional Infomation |
Appearance: White solid (as TFA salt). Molecular formula: C₅₉H₉0N10O1₅ (as free base). Storage: -80degC for long-term, -20degC for short-term. Protect from light. Solubility: Soluble in DMSO and DMF. Other names: Mal-Val-Lys-PAB-MMAE (trifluoroacetate salt). Safety: Research use only. Avoid inhalation and skin contact.
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| Molecular Formula |
C70H107F3N10O16
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|---|---|
| Molecular Weight |
1401.65
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| Related CAS # |
Mal-Val-Lys-PAB-MMAE
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 | 0.7134 mL | 3.5672 mL | 7.1344 mL | |
| 5 mM | 0.1427 mL | 0.7134 mL | 1.4269 mL | |
| 10 mM | 0.0713 mL | 0.3567 mL | 0.7134 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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