| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Microtubules (via MMAE payload). MMAE is a potent inhibitor of tubulin polymerization. By binding to tubulin, it disrupts microtubule dynamics, leading to G2/M cell cycle arrest and subsequent apoptotic cell death. The SMCC linker is non-cleavable, meaning the MMAE payload is released only after the ADC is internalized into target cancer cells and the entire antibody-linker-payload conjugate is degraded within the lysosome. This non-cleavable design reduces premature payload release and off-target toxicity.
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|---|---|
| ln Vitro |
MMAE, the active payload, potently inhibits tubulin polymerization. The MMAE-SMCC conjugate itself is not directly tested in cell-free assays; it is conjugated to antibodies for targeted delivery. The free MMAE payload has an IC50 in the low nanomolar range (0.1-1 nM) against various cancer cell lines. After conjugation to a tumor-targeting antibody via SMCC, the ADC maintains selective cytotoxicity toward antigen-positive cancer cells while sparing antigen-negative cells. The non-cleavable SMCC linker provides excellent plasma stability.
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| ln Vivo |
In mouse xenograft models of human cancer (e.g., CD30-positive or HER2-positive tumors), ADCs constructed using MMAE-SMCC as the drug-linker conjugate exhibit potent and dose-dependent antitumor activity. Treatment with the ADC (1-10 mg/kg i.v., once weekly for 2-4 weeks) results in significant tumor growth inhibition (TGI > 80%) and, in some models, complete tumor regression. The non-cleavable linker ensures that the MMAE payload remains attached to the antibody until lysosomal degradation, reducing systemic toxicity compared to cleavable linkers.
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| Enzyme Assay |
Not applicable (the drug-linker conjugate is a chemical intermediate for ADC synthesis; activity is measured for the final ADC). The conjugation efficiency of MMAE-SMCC to an antibody is monitored by hydrophobic interaction chromatography (HIC) or reversed-phase HPLC to determine drug-to-antibody ratio (DAR). Typically, the antibody is partially reduced to expose interchain thiol groups, then reacted with MMAE-SMCC at 4-25degC for 1-4 hours. Conjugation is quenched with excess cysteine, and the ADC is purified by size exclusion chromatography or dialysis. DAR is calculated based on UV absorbance at 280 nm (antibody) and 248 nm (MMAE).
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| Cell Assay |
Cancer cells expressing the target antigen (e.g., CD30+ Karpas 299 or HER2+ SK-BR-3) are seeded in 96-well plates (5,000-10,000 cells/well) and treated with varying concentrations (0.001-100 nM) of the final ADC (antibody conjugated to MMAE-SMCC) or control for 72-96 hours. Cell viability is measured by CellTiter-Glo or MTT assay. The IC50 for antigen-positive cells is typically in the sub-nanomolar to low nanomolar range. Antigen-negative cells serve as controls to assess off-target cytotoxicity. Internalization is confirmed by flow cytometry.
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| Animal Protocol |
Female athymic nude mice (6-8 weeks old, 18-22 g) bearing subcutaneous xenografts of antigen-expressing human tumor cells (e.g., Karpas 299 for CD30 or SK-BR-3 for HER2) are used when tumors reach 100-200 mm3. Mice are randomized into treatment groups (n=8-10). The ADC (1-10 mg/kg) or vehicle is administered intravenously once weekly for 2-4 weeks. Tumor volumes are measured by calipers twice weekly. Body weight is monitored for toxicity. At study termination, tumors are excised and weighed. Plasma samples are collected for PK analysis. Tumor tissues are processed for histology (Ki67, cleaved caspase-3) to assess pharmacodynamic effects.
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| ADME/Pharmacokinetics |
MMAE-SMCC is a drug-linker intermediate (MW 1140.43) and is not administered directly. Once conjugated to an antibody, the resulting ADC has a molecular weight of approximately 150-160 kDa. The ADC is administered intravenously, as oral bioavailability is negligible due to the large size. The ADC has a terminal half-life of several days (depending on the antibody) and is distributed primarily to blood, liver, spleen, and tumor tissues. The non-cleavable SMCC linker ensures that MMAE is not released prematurely in circulation.
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| Toxicity/Toxicokinetics |
MMAE-SMCC is a research chemical, not a therapeutic. The primary toxicity of ADCs constructed with MMAE-SMCC is associated with the MMAE payload and includes myelosuppression (neutropenia, thrombocytopenia), peripheral neuropathy (due to tubulin inhibition), fatigue, and gastrointestinal disturbances (nausea, diarrhea). The non-cleavable linker generally reduces off-target toxicity compared to cleavable linkers. The unconjugated linker SMCC has low inherent toxicity; MMAE is highly toxic and must be handled in a fume hood with full PPE.
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| References | |
| Additional Infomation |
MMAE-SMCC is a key building block for the synthesis of non-cleavable ADCs. ADCs containing MMAE include brentuximab vedotin (Adcetris®), which targets CD30 for Hodgkin lymphoma and anaplastic large cell lymphoma (ALCL). Brentuximab vedotin uses a protease-cleavable dipeptide linker (vc-MMAE), not SMCC. The SMCC linker is non-cleavable and provides greater plasma stability, which may be advantageous for certain targets. MMAE-SMCC is for research and ADC development only and is not a finished drug product.
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| Molecular Formula |
C??H??N?O??S
|
|---|---|
| Molecular Weight |
1140.43
|
| Exact Mass |
1139.618
|
| CAS # |
2021179-11-1
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| PubChem CID |
146014493
|
| Appearance |
White to off-white solid powder
|
| LogP |
4.1
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
15
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| Rotatable Bond Count |
29
|
| Heavy Atom Count |
80
|
| Complexity |
2170
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| Defined Atom Stereocenter Count |
10
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| SMILES |
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)N[C@H](C)[C@H](C2=CC=CC=C2)O)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N(C)C(=O)CCSC3CC(=O)N(C3=O)CC4CCC(CC4)C(=O)ON5C(=O)CCC5=O
|
| InChi Key |
KPJLIFRLZIUVFO-AREODUGYSA-N
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| InChi Code |
InChI=1S/C58H89N7O14S/c1-13-35(6)51(42(77-11)30-47(69)63-28-17-20-41(63)53(78-12)36(7)54(72)59-37(8)52(71)39-18-15-14-16-19-39)62(10)57(75)49(33(2)3)60-55(73)50(34(4)5)61(9)44(66)27-29-80-43-31-48(70)64(56(43)74)32-38-21-23-40(24-22-38)58(76)79-65-45(67)25-26-46(65)68/h14-16,18-19,33-38,40-43,49-53,71H,13,17,20-32H2,1-12H3,(H,59,72)(H,60,73)/t35-,36+,37+,38?,40?,41-,42+,43?,49-,50-,51-,52+,53+/m0/s1
|
| Chemical Name |
(2,5-dioxopyrrolidin-1-yl) 4-[[3-[3-[[(2S)-1-[[(2S)-1-[[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-methylamino]-3-oxopropyl]sulfanyl-2,5-dioxopyrrolidin-1-yl]methyl]cyclohexane-1-carboxylate
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| Synonyms |
MMAE-SMCC MMAE SMCC
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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. (3). 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) |
DMSO : ~100 mg/mL (~87.69 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.19 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 (2.19 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 (2.19 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 | 0.8769 mL | 4.3843 mL | 8.7686 mL | |
| 5 mM | 0.1754 mL | 0.8769 mL | 1.7537 mL | |
| 10 mM | 0.0877 mL | 0.4384 mL | 0.8769 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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