Monomethyl auristatin E (Synonyms: Brentuximab vedotin, MMAE) |
| カタログ番号GC17276 |
強力な抗ミトーシス化合物
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 474645-27-7
Sample solution is provided at 25 µL, 10mM.
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Monomethyl Auristatin E (MMAE), as a synthetic derivative of dolastatin 10, a linear pentapeptide originally isolated from the extracts of the sea hare Dolabella auriculari. Monomethyl Auristatin E, as a synthetic derivative of dolastatin 10, a linear pentapeptide originally isolated from the extracts of the sea hare Dolabella auriculari. Monomethyl Auristatin E can inhibit tubulin polymerization, thus blocking mitosis.[1]
In vitro, Monomethyl Auristatin E and Monomethyl Auristatin E-phosphate shown the inhibition with IC50 of 2 and 48 nM, respectively, in PC-3 and C4-2B cell lines.[1] In vitro experiment it shown that 5 nM MMAE resulted in 50% of HCT-116 cells blocked in G2/M and 2 nM in PANC-1 cells.[2] MMAE shown the inhibition of cell growth with IC50 of 1.7 nM in HCT-116, 0.6 nM in PANC-1, and 5.6 nM in 779E cells, respectively.[2] In addition, MMAE also showed markedly polarized transport in both MDCK-WT and MDCK-MDR1 cells with ERs at 13.6 and 44.5, respectively, resulting ratio of ratios of 3.3. MMAE shown dose-dependent cytotoxicity in HepG2, Hep3B2, H226, N87 or OVCAR3 cells.[3]
In vivo, treatment with 30 mg/kg cAC10-vcMMAE in mice had no signs of toxicity.[4] In vivo efficacy test it shown that treatment with 6.5 mg/kg DD1-MMAE (the bivalent DARPin dimer) or DFc-MMAE (a DARPin-Fc) twice weekly did not cause any sequela in mice.[5] Moreover, nude mice were injected intravenously 2.5, 5, and 10 mg/kg hertuzumab-vcMMAE on day 0 resulted in obvious and sustained antitumor effects. [6]
References:
[1]Abawi A, et al. Monomethyl Auristatin E Grafted-Liposomes to Target Prostate Tumor Cell Lines. Int J Mol Sci. 2021 Apr 15;22(8):4103.
[2]Buckel L, et al. Tumor radiosensitization by monomethyl auristatin E: mechanism of action and targeted delivery. Cancer Res. 2015 Apr 1;75(7):1376-1387.
[3]Liu-Kreyche P, et al. Lysosomal P-gp-MDR1 Confers Drug Resistance of Brentuximab Vedotin and Its Cytotoxic Payload Monomethyl Auristatin E in Tumor Cells. Front Pharmacol. 2019 Jul 17;10:749.
[4]Francisco JA, et al. cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood. 2003 Aug 15;102(4):1458-65.
[5]Karsten L, et al. Bivalent EGFR-Targeting DARPin-MMAE Conjugates. Int J Mol Sci. 2022 Feb 23;23(5):2468.
[6]Li H, et al. An anti-HER2 antibody conjugated with monomethyl auristatin E is highly effective in HER2-positive human gastric cancer. Cancer Biol Ther. 2016 Apr 2;17(4):346-54.
| Cell experiment [1]: | |
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Cell lines |
MCF7-R1 cells |
|
Preparation Method |
100,000 MCF7-R1 cells were seeded into each well of a 12-well culture plate, allowed to adhere overnight, and treated with 10 nM Monomethyl Auristatin E (MMAE) or conjugates in the presence of 10 U/mL heparin for 72 h. Then the cells were harvested with a TrypLE Express solution, stained by Annexin V-FITC and propidium iodide, and analyzed by flow cytometry using a NovoCyte 2060R flow cytometer. |
|
Reaction Conditions |
10 nM; for 72 h |
|
Applications |
After 72 h of treatment of MCF7-R1 cells with 10 nM conjugates, the cells were mainly in the early stage of apoptosis. |
| Animal experiment [2]: | |
|
Animal models |
Mice |
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Preparation Method |
The breast tumor models were prepared via subcutaneous injection of 1 × 106 4T1 cells. When the tumor volumes were approximately 100 mm3, mice were divided into three groups: (i) saline; (ii) Monomethyl Auristatin E (MMAE) (0.2 mg/kg); and (iii) FRRG-MMAE nanoparticles (equivalent dose of 0.2 mg/kg based on MMAE contents). The mice were treated once every three days, and tumor volumes were calculated as the smallest diameter 2 × largest diameter × 0.53. The mice with a tumor volume of 2000 mm3 or larger were counted as dead. The toxicity study of FRRG-MMAE nanoparticles was assessed via histology. |
|
Dosage form |
0.2 mg/kg |
|
Applications |
The results demonstrated that free MMAE-treated mice showed rapid tumor growth compared to FRRG-MMAE-treated mice during monitoring for 15 days.Finally, mice treated with free MMAE showed significant body weight loss owing to the severe toxicity; eventually, all the mice were dead within five days of treatment.These results show the significantly reduced MMAE-related toxicity in the FRRG-MMAE nanoparticle group. |
|
References: [1] Krzyscik MA, et al. Fibroblast Growth Factor 2 Conjugated with Monomethyl Auristatin E Inhibits Tumor Growth in a Mouse Model. Biomacromolecules. 2021 Oct 11;22(10):4169-4180. [2] Cho H, et al. Tumor-Specific Monomethyl Auristatin E (MMAE) Prodrug Nanoparticles for Safe and Effective Chemotherapy. Pharmaceutics. 2022 Oct 7;14(10):2131. |
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| Cas No. | 474645-27-7 | SDF | |
| 同義語 | Brentuximab vedotin, MMAE | ||
| 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 | ||
| Canonical SMILES | CCC(C)C(C(CC(=O)N1CCCC1C(C(C)C(=O)NC(C)C(C2=CC=CC=C2)O)OC)OC)N(C)C(=O)C(C(C)C)NC(=O)C(C(C)C)NC | ||
| Formula | C39H67N5O7 | M.Wt | 717.98 |
| 溶解度 | ≥ 35.9 mg/mL in DMSO, ≥ 48.5 mg/mL in EtOH with ultrasonic and warming | Storage | Store at -20°C, stored under nitrogen,unstable in solution, ready to use. |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.3928 mL | 6.964 mL | 13.928 mL |
| 5 mM | 0.2786 mL | 1.3928 mL | 2.7856 mL |
| 10 mM | 0.1393 mL | 0.6964 mL | 1.3928 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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