Monomethyl auristatin E
(Synonyms: 一甲基澳瑞他汀E,Vedotin; MMAE) 目录号 : GC17276
Monomethyl Auristatin E (MMAE)，作为海兔毒素 10 的合成衍生物，海兔毒素 10 是一种线性五肽，最初是从海兔 Dolabella auriculari 的提取物中分离出来的。
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.
Monomethyl Auristatin E (MMAE)，作为海兔毒素 10 的合成衍生物，海兔毒素 10 是一种线性五肽，最初是从海兔 Dolabella auriculari 的提取物中分离出来的。 Monomethyl Auristatin E，作为海兔毒素 10 的合成衍生物，海兔毒素 10 是一种线性五肽，最初是从海兔 Dolabella auriculari 的提取物中分离出来的。单甲基 Auristatin E 可以抑制微管蛋白聚合，从而阻断有丝分裂。[1]
在体外，Monomethyl Auristatin E 和 Monomethyl Auristatin E-phosphate 在 PC-3 和 C4-2B 细胞系中的 IC50 分别为 2 和 48 nM。[1]体外实验表明，5 nM MMAE 导致 50% 的 HCT-116 细胞在 G2/M 期受阻，2 nM 在 PANC-1 细胞中受阻。[2] MMAE 显示出抑制细胞生长的 IC50在 HCT-116 中为 1.7 nM，在 PANC-1 中为 0.6 nM，在 779E 细胞中为 5.6 nM。[2] 此外，MMAE 在 MDCK-WT 和 MDCK 中也表现出明显的极化转运-ER 分别为 13.6 和 44.5 的 MDR1 细胞，所得比率为 3.3。 MMAE 在 HepG2、Hep3B2、H226、N87 或 OVCAR3 细胞中表现出剂量依赖性细胞毒性。[3]
在体内，用 30 mg/kg cAC10-vcMMAE 处理小鼠没有毒性迹象。[4] 体内药效试验表明，用 6.5 mg/kg DD1-MMAE 处理（二价 DARPin 二聚体）或 DFc-MMAE（一种 DARPin-Fc）每周两次在小鼠体内未引起任何后遗症。[5] 此外，裸鼠静脉注射 2.5、5 和 10 mg/ kg hertuzumab-vcMMAE 在第 0 天产生明显和持续的抗肿瘤作用。 [6]
| Cell experiment [1]: | |
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Cell lines |
MCF7-R1 cells |
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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]: | |
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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. |
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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 | |
| 别名 | 一甲基澳瑞他汀E,Vedotin; MMAE | ||
| 化学名 | (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 | ||
| 分子式 | C39H67N5O7 | 分子量 | 717.98 |
| 溶解度 | ≥ 35.9 mg/mL in DMSO, ≥ 48.5 mg/mL in EtOH with ultrasonic and warming | 储存条件 | Store at -20°C, stored under nitrogen,unstable in solution, ready to use. |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet