Lenvatinib (E7080)
(Synonyms: 仑伐替尼; E7080) 目录号 : GC15454
E7080，称为乐伐替尼，是一种口服多靶点酪氨酸激酶抑制剂，包括 VEGF、FGF 和 SCF 受体，已被证明可以提高放射性碘难治性甲状腺癌患者的生存率。
Cas No.:417716-92-8
Sample solution is provided at 25 µL, 10mM.
E7080, known as lenvatinib, is an oral multitargeted tyrosine kinase inhibitor including VEGF, FGF and SCF receptors that has been shown to improve the survival rate of patients with radioiodine-refractory thyroid cancer. Lenvatinib (E7080) had antitumor activity against HCC PDX models, likely through its potent anti-angiogenic activity [1].
Lenvatinib (E7080) inhibited Flt-1, KDR, Flt-4 with IC50 values of 22, 4.0 and 5.2 nM, respectively. Lenvatinib (E7080) inhibited FGFR1 and FDGFR tyrosine kinases. In addition to these kinases, Lenvatinib (E7080) also inhibited KIT kinase with an IC50 value of 100 nM [2]. The half-maximal inhibitory concentrations (IC50 ) for Lenvatinib (E7080) treatment of 8505C and TCO1 cells were 24.26 and 26.32 μM, respectively [3].
The novel multi-targeted kinase inhibitor Lenvatinib (E7080), which inhibited both KDR and KIT kinases, showed a more potent antitumor efficacy against H146 tumor than imatinib. Oral administration of Lenvatinib (E7080) inhibited the growth of H146 tumor at 30 and 100 mg/kg in a dose-dependent manner and caused tumor regression at 100 mg/kg [2]. Lenvatinib (E7080) at 10 and 30 mg/kg inhibited the tumor growth of both PDXs, LI0050 and LI0334 [1]. Lenvatinib (E7080), as compared with placebo, was associated with significant prolongation of progression-free survival and an improved response rate (64.8% vs. 1.5%) among patients with iodine-131–refractory differentiated thyroid cancer [4].
References:
[1].Matsuki M, Hoshi T, Yamamoto Y, Ikemori-Kawada M, Minoshima Y, Funahashi Y, Matsui J. Lenvatinib inhibits angiogenesis and tumor fibroblast growth factor signaling pathways in human hepatocellular carcinoma models. Cancer Med. 2018 Jun;7(6):2641-2653.
[2].Matsui J, Yamamoto Y, Funahashi Y, Tsuruoka A, Watanabe T, Wakabayashi T, Uenaka T, Asada M. E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition. Int J Cancer. 2008 Feb 1;122(3):664-71.
[3].Enomoto K, Hirayama S, Kumashiro N, Jing X, Kimura T, Tamagawa S, Matsuzaki I, Murata SI, Hotomi M. Synergistic Effects of Lenvatinib (E7080) and MEK Inhibitors against Anaplastic Thyroid Cancer in Preclinical Models. Cancers (Basel). 2021 Feb 18;13(4):862.
[4].Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, Habra MA, Newbold K, Shah MH, Hoff AO, Gianoukakis AG, Kiyota N, Taylor MH, Kim SB, Krzyzanowska MK, Dutcus CE, de las Heras B, Zhu J, Sherman SI. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015 Feb 12;372(7):621-30.
E7080,称为乐伐替尼,是一种口服多靶点酪氨酸激酶抑制剂,包括 VEGF、FGF 和 SCF 受体,已被证明可以提高放射性碘难治性甲状腺癌患者的生存率。 Lenvatinib (E7080) 对 HCC PDX 模型具有抗肿瘤活性,这可能是通过其有效的抗血管生成活性[1]。
Lenvatinib (E7080) 抑制 Flt-1、KDR、Flt-4,IC50 值分别为 22、4.0 和 5.2 nM。 Lenvatinib (E7080) 抑制 FGFR1 和 FDGFR 酪氨酸激酶。除了这些激酶,乐伐替尼 (E7080) 还抑制 KIT 激酶,IC50 值为 100 nM [2]。 Lenvatinib (E7080) 处理 8505C 和 TCO1 细胞的半数最大抑制浓度 (IC50 ) 分别为 24.26 和 26.32 μM [3]。
新型多靶点激酶抑制剂乐伐替尼 (Lenvatinib) (E7080) 可同时抑制 KDR 和 KIT 激酶,对 H146 肿瘤显示出比伊马替尼更有效的抗肿瘤功效。口服乐伐替尼 (E7080) 在 30 和 100 mg/kg 时以剂量依赖性方式抑制 H146 肿瘤的生长,在 100 mg/kg 时引起肿瘤消退 [2]。 10 和 30 mg/kg 的乐伐替尼 (E7080) 抑制了 PDX、LI0050 和 LI0334 的肿瘤生长[1]。与安慰剂相比,乐伐替尼 (E7080) 与碘 131 难治性分化型甲状腺癌患者的无进展生存期显着延长和缓解率提高（64.8% 对 1.5%）相关[4] .
| Kinase experiment [1]: | |
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Preparation Method |
4μL of serial dilutions of Lenvatinib (E7080) were mixed in a 96-well round plate with 10μL of enzyme (KDR), 16μL of poly (GT) solution (250 ng) and 10μL of ATP solution (1μmol/L ATP) (final concentration of DMSO was 0.1%).The kinase reaction was initiated by adding ATP solution to each well. After 30-min incubation at 30°C, the reaction was stopped by adding 0.5 mol/L EDTA (10μL/well) to the reaction mixture in each well. HTRF solution (50μL/well) was added to the reaction mixture, and then kinase activity was determined by measurement of fluorescence with a time-resolved fluorescence detector at an excitation wavelength of 337 nm and an emission wave-lengths of 620 and 665 nm. |
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Reaction Conditions |
4μL,30 min |
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Applications |
Lenvatinib (E7080) inhibited KDR with IC50 values of 4.0 nM. |
| Cell experiment [2]: | |
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Cell lines |
8505C and TCO1 cell |
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Preparation Method |
The cells were grown in 96-well microplates in a final volume of 100 μL culture medium per well. The cells were incubated with 0.1 to 50 μM Lenvatinib (E7080) for 48 h. Then, 50 μL of the XTT labeling mixture was added to each well to a final XTT concentration of 0.3 mg/mL. After incubation of the microplate for 4 h in 5% CO2 at 37 °C in a humidified incubator, the formazan dye formed was quantified using a scanning multiwell spectrophotometer. |
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Reaction Conditions |
0.1 to 50 μM Lenvatinib (E7080) for 48 h |
|
Applications |
The half-maximal inhibitory concentrations (IC50) for Lenvatinib (E7080) treatment of 8505C and TCO1 cells were 24.26 and 26.32 μM, respectively. |
| Animal experiment [1]: | |
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Animal models |
Female BALB/c nude mice (8–12 weeks old, 20–25 g) |
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Preparation Method |
H146 tumor cells (6.5×106) were implanted subcutaneously into the flank region of mice. Twelve days after inoculation, mice were randomized into control (n=12) and treatment groups (n=6) and this point in time was identified as day 1. Lenvatinib (E7080) were suspended in 0.5% methylcellulose and saline, and administered orally twice a day for Lenvatinib (E7080) from day 1 to day 21. Tumor volume was measured on the indicated days and calculated. |
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Dosage form |
Administer orally twice a day for Lenvatinib (E7080) |
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Applications |
Oral administration of Lenvatinib (E7080) inhibited the growth of H146 tumor at 30 and 100 mg/kg in a dose-dependent manner and caused tumor regression at 100 mg/kg. |
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References: [1]. Matsui J, Yamamoto Y, Funahashi Y, Tsuruoka A, Watanabe T, Wakabayashi T, Uenaka T, Asada M. E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition. Int J Cancer. 2008 Feb 1;122(3):664-71. [2]. Enomoto K, Hirayama S, Kumashiro N, Jing X, Kimura T, Tamagawa S, Matsuzaki I, Murata SI, Hotomi M. Synergistic Effects of Lenvatinib (E7080) and MEK Inhibitors against Anaplastic Thyroid Cancer in Preclinical Models. Cancers (Basel). 2021 Feb 18;13(4):862. |
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| Cas No. | 417716-92-8 | SDF | |
| 别名 | 仑伐替尼; E7080 | ||
| 化学名 | 4-[3-chloro-4-(cyclopropylcarbamoylamino)phenoxy]-7-methoxyquinoline-6-carboxamide | ||
| Canonical SMILES | COC1=CC2=NC=CC(=C2C=C1C(=O)N)OC3=CC(=C(C=C3)NC(=O)NC4CC4)Cl | ||
| 分子式 | C21H19ClN4O4 | 分子量 | 426.85 |
| 溶解度 | DMSO: 8.33 mg/mL (15.93 mM) | 储存条件 | Store at 4°C, protect from light |
| 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 | 2.3427 mL | 11.7137 mL | 23.4274 mL |
| 5 mM | 0.4685 mL | 2.3427 mL | 4.6855 mL |
| 10 mM | 0.2343 mL | 1.1714 mL | 2.3427 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
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Related Biological Data
Characterization of the different NPs. (F) Diameters and (G) zeta potentials of the different NPs.
We also determined the cytotoxicity of pure Len on Hepa1:6 by culturing Hepa1:6 cell with gradient concentrations of Len (GLPBIO) (5, 10, 20, 30, 40, 50, 60, 70 μg mL -1 ).
Acta Biomaterialia 154 (2022): 478-496. PMID: 36280029 IF: 9.7004 -
Related Biological Data
(D) In vitro cytotoxicity of mSiO2-FA, free Le, free drugs Bu-Le combination, Bu@mSiO2-FA, Le@mSiO2-FA, Bu/Le@ mSiO2-FA by CCK8 assay.
Bufalin (Bu) and Lenvatinib (Le) were purchased from GLPBIO (Montclair, CA, USA)
Nanomaterials 12.12 (2022): 2048. PMID: 35745387 IF: 5.076