| CAS |
No.745017-94-1 |
| 英文名称 |
MMAF |
| 分子式 |
C39H65N5O8 |
| 分子量 |
731.96 |
| 溶解性 |
Soluble in DMSO ≥10mg/mL(该产品在溶液状态不稳定，建议您现用现配) |
| 纯度 |
≥98% |
| 外观(性状) |
White to off-white Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| 靶点 |
Microtubule/Tubulin |
| 通路 |
Cytoskeleton |
| 背景说明 |
MMAF 是一种有效的微管蛋白聚合 (tubulin polymerization) 抑制剂，，通过阻断微管蛋白的聚合来抑制细胞分裂，广泛用作抗体偶联药物 (ADCs) 的细胞毒性成分，如 Vorsetuzumab mafodotin 和 SGN-CD19A。 |
| 生物活性 |
MMAF (Monomethylauristatin F) is a potent tubulin polymerization inhibitor and is used as a antitumor agent. MMAF (Monomethylauristatin F) is widely used as a cytotoxic component of antibody-drug conjugates (ADCs) such as vorsetuzumab mafodotin and SGN-CD19A.[1-4] |
| In Vitro |
MMAF inhibits anaplastic large cell lymphoma Karpas 299， breast carcinoma H3396， renal cell carcinoma 786-O and Caki-1 cells with IC50s of 119， 105， 257 and 200 nM in vitro cytotoxicity assay[4]. |
| In Vivo |
小鼠的最大耐受剂量 (MTD) MMAF (>16 mg/kg) 远高于 MMAE (1 mg/kg)。cAC10-L1-MMAF4 对小鼠的 MTD 为 50 mg/kg，对大鼠的 MTD 为 15 mg/kg。相应的 cAC10-L4-MMAF4 ADC 的毒性更小，小鼠和大鼠的 MTDs 分别 >150 mg/kg 和 90 mg/kg[4]。 |
| 细胞实验 |
Cells are treated with serial dilutions of test molecules and incubated 4-6 days depending on cell line. Assessment of cellular growth and data reduction to generate IC50 values is done using Alamar Blue dye reduction assay[2]. |
| 动物实验 |
Mice: When subcutaneous Karpas 299 tumor size reaches 300 mm3， three animals per group receives one injection of 10 mg antibody component/kg body weight of either cAC10-L1-MMAF4 or cBR96-L1-MMAF4 intravenously. Tumors are then removed and placed in optimal cutting temperature compound， and 5 μm-thin frozen tissue sections are stained using immunohistochemistry evaluation[1]. |
| 数据来源文献 |
[1]. Lee JW， et al. EphA2 targeted chemotherapy using an antibody drug conjugate in endometrial carcinoma. Clin Cancer Res. 2010 May 1;16(9):2562-70.
[2]. Lee JJ， et al. Enzymatic prenylation and oxime ligation for the synthesis of stable and homogeneous protein-drug conjugates for targeted therapy. Angew Chem Int Ed Engl. 2015 Oct 5;54(41):12020-4.
[3]. Kim EG， et al. Strategies and Advancement in Antibody-Drug Conjugate Optimization for Targeted CancerTherapeutics.
[4]. Doronina SO， et al. Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: effects of linker technology on efficacy and toxicity. Bioconjug Chem. 2006 Jan-Feb;17(1):114-24. |
| 规格 |
1mg 5mg 10mg 25mg 50mg 100mg |
| 单位 |
瓶 |
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