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| Targets |
Auristatin
Microtubules/Tubulin. MMAE, the payload, is a synthetic analog of dolastatin 10. It acts as a potent tubulin inhibitor by binding to tubulin and inhibiting its polymerization, leading to G2/M cell cycle arrest and the induction of apoptosis in dividing cells. The vc linker is designed to be cleaved by cathepsin B, an enzyme that is overexpressed in the lysosomes of many cancer cells. |
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| ln Vitro |
SGD-1010, also known as monomethyl auristatin E (MMAE), is a synthetic version of dolastatin 10 that inhibits tubulin polymerization, a powerful mitotic inhibitor. As a cytotoxic component of antibody-drug conjugates (ADCs), MMAE is frequently used to treat a variety of cancer types.
In vitro, N3-PEG3-vc-PAB-MMAE shows potent anti-proliferative activity against various cancer cell lines after being released from an ADC. The free conjugate itself is cell-permeable and exhibits sub-nanomolar IC50 values against cancer cells, as it can enter cells and be cleaved by intracellular cathepsins. It is highly cytotoxic due to the potency of the MMAE payload. |
| ln Vivo |
No specific in vivo efficacy data is available for the free conjugate, as it is a research tool for ADC synthesis. However, ADCs constructed using this linker-payload (the vc-MMAE chemistry) have shown potent in vivo anti-tumor activity in numerous murine xenograft models (e.g., HER2-expressing tumors). These ADCs induce complete tumor regressions in some models at well-tolerated doses.
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| Enzyme Assay |
N3-PEG3-vc-PAB-MMAE itself is a chemical entity, not a biological molecule, so it is not used in standard binding assays. The payload (MMAE) is known to bind to tubulin with high affinity. A non-cellular tubulin polymerization assay can be used to confirm the activity of the released MMAE. In this assay, purified tubulin is incubated with GTP, and the rate of polymerization is measured spectrophotometrically (OD340) in the presence of varying concentrations of free MMAE.
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| Cell Assay |
In vitro cytotoxicity assays (e.g., CellTiter-Glo) are used to evaluate the potency of the free N3-PEG3-vc-PAB-MMAE conjugate or the intact ADC. Cancer cells (e.g., NCI-N87 or SK-BR-3 cells) are seeded in 96-well plates and treated with serial dilutions of the test article for 72-96 hours. Cell viability is quantified by measuring luminescence, and the IC50 (concentration that kills 50% of cells) is calculated. For a target-specific ADC, a comparison of cytotoxicity on target-positive vs. target-negative cell lines is performed to demonstrate specificity.
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| Animal Protocol |
Standard in vivo animal studies are conducted using a human xenograft model in immunocompromised mice. For an ADC built with this linker-payload, mice bearing subcutaneous human tumor xenografts (e.g., HER2-expressing NCI-N87 gastric cancer cells) are administered the ADC intravenously (i.v.) at various doses (e.g., 1, 3, 10 mg/kg). The dosing schedule is often a single dose or a Q4D x 4 schedule. Tumor volumes are measured every 3-4 days with calipers, and the primary endpoint is tumor growth inhibition (TGI) or regression.
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| ADME/Pharmacokinetics |
This drug-linker conjugate is a research chemical and its pharmacokinetic (PK) profile is not independently established. Once conjugated to an antibody, the ADC's PK is largely dictated by the antibody's properties, including a long half-life (t1/2 of several days) and low clearance. The linker is stable in circulation (which prevents premature release of MMAE) but cleavable in the target cell's lysosome, which is the ideal design feature for a safe and effective ADC.
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| Toxicity/Toxicokinetics |
The toxicity profile of this drug-linker conjugate, when administered as a free agent, would be severe and is not well-defined, as it is intended for targeted delivery via an ADC. The payload, MMAE, is a highly potent antimitotic agent with known class-related toxicities, including neutropenia (bone marrow suppression), peripheral neuropathy, and fatigue. The linker is designed to be stable, but any off-target release would cause these toxicities.
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| Additional Infomation |
This compound is a specialized building block for the synthesis of antibody-drug conjugates (ADCs). The presence of the azide (N3) group makes it a "click chemistry" reagent, allowing for facile and specific conjugation to antibodies or other targeting ligands that have been modified with a DBCO or alkyne group. This particular linker-payload combination (valine-citrulline-PAB-MMAE) is the same technology used in several FDA-approved ADCs, including brentuximab vedotin and polatuzumab vedotin, highlighting its clinical relevance as a validated platform.
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| Molecular Formula |
C67H109N13O16
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| Molecular Weight |
1352.66
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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: This product is not stable in solution, please use freshly prepared working solution for optimal results. |
| 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 | 0.7393 mL | 3.6964 mL | 7.3928 mL | |
| 5 mM | 0.1479 mL | 0.7393 mL | 1.4786 mL | |
| 10 mM | 0.0739 mL | 0.3696 mL | 0.7393 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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