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| 25mg |
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| 100mg |
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Purity: ≥98%
Monomethyl auristatin E (also known as MMAE; SGD-1010), a dolastatin 10 derivative, is a novel, synthetic and potent antimitotic/antitubulin agent which blocks the polymerization of tubulin, due to its high toxicity, it cannot be used as a drug itself; instead, it is linked to a monoclonal antibody (MAB) which directs it to the cancer cells. Vedotin, as used in the commercial drug Brentuximab vedotin, is MMAE plus the structure that connects it to the antibody (Brentuximab). In preclinical studies, both in vitro and in vivo, dolastatins—peptides found in the marine shell-less mollusc Dolabella auricularia—show strong activity against a variety of lymphomas, leukemia, and solid tumors. These peptides are the source of MMAE, a powerful antimitotic medication. When MMAE is used to treat Hodgkin lymphoma and other cancers, its potency can reach 200 times that of vinblastine, another antimitotic medication.
| Targets |
Auristatin
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|---|---|
| ln Vitro |
In CD30+ cells, MMAE exhibits selective cytotoxicity when combined with cAC10. It also causes apoptosis, which results in G2/M-phase growth arrest and cell death. [1]
Anti-CD79b-vcMMAE exhibits strong and extensive activity on a wide range of NHL cell lines when combined with anti-CD79b antibody in vitro.[2] Hertuzumab-vc-MMAE can also be efficiently internalized and significantly kill tumor cells that overexpress HER2 when combined with anti-HER2 antibody.[3] |
| ln Vivo |
While free MMAE (0.36 mg/kg) does not exhibit any discernible antitumor activity, cAC10-vcMMAE (1 mg/kg, i.v.) causes total, long-lasting tumor regression in the Karpas 299 ALCL model.[1]
Anti-CD79b-vcMMAE (7 mg/kg, p.o.) notably causes a sustained total tumor remission in mouse xenograft models of NHL. [/2] |
| Cell Assay |
As directed by the manufacturer, the Alamar Blue dye reduction assay is used to quantify cytotoxicity. In short, right before cultures are added, a freshly prepared 40% (wt/vol) solution of Alamar Blue is added to complete media. Alamar Blue solution is added to cells to make up 10% of the culture volume ninety-two hours after the drug is exposed. A Fusion HT fluorescent plate reader (Packard Instruments, Meriden, CT) is used to measure dye reduction after 4 hours of incubation of the cells.
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| Animal Protocol |
Mice: Female athymic nu/nu mice aged 6-8 weeks are given a 1:1 Matrigel and PBS solution subcutaneously injected into their thighs, containing 5×106 HCT-116 or PANC-1 cells. After administering ACPP-cRGD-MMAE intravenously (IV) or orally (IR) (6 nmoles/day, totaling 18 nmoles), the mice are given the treatment. Tumor tissue is then removed, paraffin embedded, formalin fixed, and stained with the appropriate antibodies. Using the UltraMap system, DAB is used as a chromagen and the primary antibody is used at a 1:250 dilution for visualization.
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| References | |
| Additional Infomation |
Monomethyl Auristatin E is a dolastatin-10 peptide derivative with potent antimitotic activity and potential antineoplastic activity as part of an antibody-drug conjugate (ADC). Monomethyl auristatin E (MMAE) binds to tubulin, blocks tubulin polymerization, and inhibits microtubule formation, which results in both disruption of mitotic spindle assembly and arrest of tumor cells in the M phase of the cell cycle. To minimize toxicity and maximize efficacy, MMAE is conjugated, via a cleavable peptide linker, to a monoclonal antibody that specifically targets a patient's tumor. The linker is stable in the extracellular milieu but is readily cleaved to release MMAE following binding and internalization of the ADC by the target cells.
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| Molecular Formula |
C39H67N5O7
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|---|---|---|
| Molecular Weight |
717.98
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| Exact Mass |
717.504
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| Elemental Analysis |
C, 65.24; H, 9.41; N, 9.75; O, 15.60
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| CAS # |
474645-27-7
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| Related CAS # |
MMAE-d8;2070009-72-0;Monomethyl auristatin E;474645-27-7
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| PubChem CID |
11542188
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| Appearance |
white solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
873.5±65.0 °C at 760 mmHg
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| Flash Point |
482.1±34.3 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| Index of Refraction |
1.519
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| LogP |
4.13
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
20
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| Heavy Atom Count |
51
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| Complexity |
1100
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| Defined Atom Stereocenter Count |
10
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| SMILES |
O(C([H])([H])[H])[C@]([H])([C@]([H])(C(N([H])[C@]([H])(C([H])([H])[H])[C@@]([H])(C1C([H])=C([H])C([H])=C([H])C=1[H])O[H])=O)C([H])([H])[H])[C@]1([H])C([H])([H])C([H])([H])C([H])([H])N1C(C([H])([H])[C@]([H])([C@]([H])([C@@]([H])(C([H])([H])[H])C([H])([H])C([H])([H])[H])N(C([H])([H])[H])C([C@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C([C@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C([H])([H])[H])=O)=O)OC([H])([H])[H])=O
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| InChi Key |
DASWEROEPLKSEI-UIJRFTGLSA-N
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| InChi Code |
InChI=1S/C39H67N5O7/c1-13-25(6)34(43(10)39(49)33(24(4)5)42-38(48)32(40-9)23(2)3)30(50-11)22-31(45)44-21-17-20-29(44)36(51-12)26(7)37(47)41-27(8)35(46)28-18-15-14-16-19-28/h14-16,18-19,23-27,29-30,32-36,40,46H,13,17,20-22H2,1-12H3,(H,41,47)(H,42,48)/t25-,26+,27+,29-,30+,32-,33-,34-,35+,36+/m0/s1
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| Chemical Name |
(2S)-N-[(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]-3-methyl-2-(methylamino)butanamide
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| Synonyms |
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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). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. (2). This product is not stable in solution, please use freshly prepared working solution for optimal results. |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.62 mg/mL (3.65 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.62 mg/mL (3.65 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. 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 (3.48 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. Solubility in Formulation 4: ≥ 2.5 mg/mL (3.48 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. Solubility in Formulation 5: ≥ 2.5 mg/mL (3.48 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. Solubility in Formulation 6: ≥ 2.5 mg/mL (3.48 mM) (saturation unknown) in 10% EtOH + 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 EtOH 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 7: ≥ 2.5 mg/mL (3.48 mM) (saturation unknown) in 10% EtOH + 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 EtOH 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. Solubility in Formulation 8: ≥ 2.5 mg/mL (3.48 mM) (saturation unknown) in 10% EtOH + 90% Corn Oil (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 EtOH stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 9: ≥ 0.52 mg/mL (0.72 mM) (saturation unknown) in 1% DMSO + 99% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3928 mL | 6.9640 mL | 13.9280 mL | |
| 5 mM | 0.2786 mL | 1.3928 mL | 2.7856 mL | |
| 10 mM | 0.1393 mL | 0.6964 mL | 1.3928 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.
 MMAE has increased potency compared to paclitaxel in tumor cells.Cancer Res.2015 Apr 1;75(7):1376-1387. |
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 MMAE increases IR induced DNA double strand breaks in a schedule and dose dependent manner.Cancer Res.2015 Apr 1;75(7):1376-1387. |
 MMAE decreases clonogenic survival of irradiated tumor cells.Cancer Res.2015 Apr 1;75(7):1376-1387. |
 MMAE increases DNA damage response in irradiated tumor cells.Cancer Res.2015 Apr 1;75(7):1376-1387. |
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 ACPP-cRGD-MMAE in combination with IR significantly reduces tumor growth.Cancer Res.2015 Apr 1;75(7):1376-1387. |
 Activatable cell penetrating peptides are cleaved in irradiated tumor microenvironments.A)Orthotopic pancreatic adenocarcinoma PDX were harvested and zymography gels used to assess gelatinase activity, lysates. For each PDX, lysates were run in duplicate (lanes A and B).Cancer Res.2015 Apr 1;75(7):1376-1387. |
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