| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
The biological target of the MMAE component is tubulin. Once the ADC is internalized into a target cancer cell, the linker is cleaved by lysosomal proteases (cathepsins), releasing the active MMAE. MMAE then binds to the Vinca alkaloid binding site on tubulin, inhibiting tubulin polymerization. This blocks mitosis (cell division) at the G2/M phase and induces apoptosis (programmed cell death). The VC-PAB linker is designed for stability in circulation (plasma) and efficient cleavage in the lysosomes of cancer cells. The 2-MSP-5-HA portion likely provides solubility and enhances conjugation efficiency.
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| ln Vitro |
As a drug-linker conjugate, the in vitro activity of the intact construct is low because it requires enzymatic cleavage to release the active MMAE. In a cell-free system, it is not active. To measure potency, the conjugate must first be conjugated to an antibody. The resulting ADC is then tested on antigen-positive cancer cells. The ADC is internalized, the linker is cleaved, and the released MMAE kills the cells. The IC50 of the ADC is typically in the low nanomolar (or sub-nanomolar) range. The free MMAE (parent payload) has an IC50 of 0.1-5 nM against various cancer cell lines (e.g., HCT116, HeLa). The drug-linker is a precursor to the active therapeutic.
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| ln Vivo |
ADCs constructed using 2-MSP-5-HA-VC-PAB-MMAE have been tested in vivo in xenograft mouse models. The ADC is administered intravenously (e.g., 1-10 mg/kg, once weekly for 3 weeks) to mice bearing subcutaneous human tumor xenografts that express the target antigen. The ADC demonstrates potent, dose-dependent tumor growth inhibition (TGI) and often complete tumor regression. The efficacy is superior to non-targeting control ADCs (using an irrelevant antibody) or vehicle control. The VC-PAB linker demonstrates high stability in circulation (low release of free MMAE in plasma), contributing to a favorable therapeutic window (high efficacy, low toxicity).
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| Enzyme Assay |
Not applicable. The drug-linker conjugate is not used in enzyme or receptor binding assays in its intact form. The binding affinity of the final ADC is measured using Surface Plasmon Resonance (SPR) or ELISA. The target antigen (e.g., a tumor-associated antigen) is immobilized on a sensor chip or plate. The ADC is flowed over the chip, and the binding affinity (KD) is calculated. For the linker cleavage assay, recombinant cathepsin B is incubated with the drug-linker or the ADC at 37degC (pH 5.5). The release of MMAE is measured by LC-MS/MS over time. Rapid cleavage (within 1-4 hours) confirms linker functionality.
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| Cell Assay |
Not applicable. The drug-linker conjugate is typically conjugated to an antibody before cell testing. To test the potency of the final ADC, target antigen-positive cancer cells (e.g., 5,000 cells/well) are seeded in 96-well plates. Serial dilutions of the ADC (0.001-100 nM) are added. After 96-120 hours, cell viability is measured by CellTiter-Glo. The IC50 (concentration for 50% growth inhibition) is calculated. A non-binding control ADC (isotype control) is used to confirm that the killing is antigen-specific. Typically, the specific ADC has an IC50 of 0.1-10 nM, while the control ADC has an IC50 > 100 nM. Apoptosis is confirmed by measuring caspase 3/7 activity.
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| Animal Protocol |
For in vivo testing, the ADC is formulated in a vehicle such as PBS (phosphate-buffered saline) with 0.01% Tween-80. It is administered intravenously via tail vein injection. For a xenograft study, immunocompromised mice (e.g., nude or NSG, 6-8 weeks) are injected subcutaneously with target antigen-positive tumor cells (e.g., 5 x 10⁶ cells/mouse). When tumors reach 150-200 mm3 (typically 7-14 days), mice are randomized into groups (n=6-10). The ADC is dosed at 1, 3, and 10 mg/kg, typically once weekly for 2-4 weeks. Tumor volumes are measured bi-weekly with calipers. Body weight is monitored as a toxicity indicator. At study termination, tumors are weighed, and tumor growth inhibition (TGI%) is calculated.
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| ADME/Pharmacokinetics |
The linkers used in this conjugate are optimized for a favorable pharmacokinetic profile, providing a balance between circulation stability and intratumoral release. The ADC is expected to have a long half-life (several days) and low clearance. The released MMAE is rapidly cleared (minutes).
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| Toxicity/Toxicokinetics |
The conjugate helps concentrate the MMAE in the tumor, minimizing systemic exposure and toxicity. The 2-MSP-5-HA-VC-PAB-MMAE linker is designed to be stable in plasma, with less than 5% payload release over 14 days at 37degC when tested in mouse plasma. This stability is critical for preventing premature drug release, which would cause off-target toxicity (e.g., neutropenia). The VC-PAB sequence is a known substrate for cathepsin B, an enzyme that is upregulated in many cancer cells. This linker technology has been clinically validated in several FDA-approved ADCs (e.g., brentuximab vedotin, enfortumab vedotin). The drug-linker is stored at -20degC, protected from light. It is soluble in DMSO. The compound has CAS number 2878440-80-1. Its molecular weight is high (typically >1000 Da for such conjugates). The 2-MSP-5-HA is a hydrophilic moiety designed to improve the solubility and conjugation efficiency of the highly lipophilic MMAE payload. The 5-HA portion likely stands for a 5-hydroxy link or spacer. The drug-linker is an advanced intermediate; the final ADC is the therapeutic agent.
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| References |
| Molecular Formula |
C69H104N12O15S
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|---|---|
| Molecular Weight |
1373.70
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| CAS # |
2878440-80-1
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). 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) |
DMSO : ≥ 100 mg/mL (~72.80 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.7280 mL | 3.6398 mL | 7.2796 mL | |
| 5 mM | 0.1456 mL | 0.7280 mL | 1.4559 mL | |
| 10 mM | 0.0728 mL | 0.3640 mL | 0.7280 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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