Lenvatinib (E7080)
Lenvatinib (E7080) is an inhibitor of multiple RTK with IC50 values of 22 nM, 4 nM, 5.2 nM, 39 nM and 35 nM on VEGFR-1, VEGFR-2, VEGFR-3, PDGFRβ and RET, respectively [1].
Lenvatinib is presently under investigation both as monotherapy and in combination with cytotoxic agents for multiple types of solid tumor, including thyroid carcinoma and hepatocellular carcinoma (in Phase III trials), and melanoma, renal carcinoma, non-small cell lung carcinoma, glioblastoma multiforme, and ovarian and endometrial carcinoma (Phase I and II trials) [1].
When used as an inhibitor of RET kinase, Lenvatinib cause growth inhibition in TPC-1 cells and LC-2/ad cells. The GI50 values are 27 nM and 48 nM. It is also reported that Lenvatinib can inhibit RET (rearranged during transfection) gene fusion kinases, and inhibit oncogenic signaling of RET gene fusions. Lenvatinib has been demonstrated to exert antitumor activities in RET gene fusion-driven tumor models [2].
References:
[1] Neda Stjepanovic, Jaume Capdevila. Multikinase inhibitors in the treatment of thyroid cancer: specific role of lenvatinib. Biologics: Targets and Therapy. 2014 (8): 129-139.
[2] Kiyoshi Okamoto, Kotaro Kodama, Kazuma Takase, Naoko Hata Sugi, Yuji Yamamoto, Masao Iwata, Akihiko Tsuruoka. Antitumor activities of the targeted multi-tyrosine kinase inhibitor lenvatinib (E7080) against RET gene fusion-driven tumor models. Cancer Letters. 2013 July (340): 97-103.
- 1. Yarong Guo, Bao Chai, et al. "RARRES1 inhibits hepatocellular carcinoma progression and increases its sensitivity to lenvatinib through interaction with SPINK2." Biol Direct. 2024 Feb 23;19(1):15 PMID: 38388961
- 2. Xin Han, Jianhua Wu, et al. "Dicer Suppresses Hepatocellular Carcinoma via Interleukin-8 Pathway." Clin Med Insights Oncol. 2023 Apr 7:17:11795549231161212. PMID: 37056297
- 3. Xudong Xie, Li Li 1, et al. "Proto-Oncogene FAM50A can Regulate the Immune Microenvironment and Development of Hepatocellular Carcinoma In Vitro and In Vivo." Int J Mol Sci. 2023 Feb 6;24(4):3217. PMID: 36834630
| Storage | Store at -20°C |
| M.Wt | 426.85 |
| Cas No. | 417716-92-8 |
| Formula | C21H19ClN4O4 |
| Solubility | ≥21.35 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O |
| Chemical Name | 4-[3-chloro-4-(cyclopropylcarbamoylamino)phenoxy]-7-methoxyquinoline-6-carboxamide |
| SDF | Download SDF |
| Canonical SMILES | COC1=CC2=NC=CC(=C2C=C1C(=O)N)OC3=CC(=C(C=C3)NC(=O)NC4CC4)Cl |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
|
Cell lines |
HUVECs |
|
Preparation method |
The solubility of this compound in DMSO is >21.4 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37°C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months. |
|
Reacting condition |
0~10 μM; 72 hrs |
|
Applications |
In HUVECs stimulated with VEGF and VEGF-C, Lenvatinib strongly inhibited VEGF-R2 and VEGF-R3 with the IC50 values of 0.83 nM and 0.36 nM, respectively. In addition, E7080 showed stronger inhibitory activity against VEGF-induced proliferation of HUVECs (IC50 = 2.7 nmol/L) than basic FGF-induced proliferation of HUVECs (IC50 = 410 nM) and PDGF-induced proliferation of L cells (IC50 = 340 nM). |
| Animal experiment [1]: | |
|
Animal models |
Nude mice bearing MDA-MB-231 cells |
|
Dosage form |
100 mg/kg; p.o.; q.d., for 8 weeks |
|
Applications |
In nude mice bearing MDA-MB-231 cells, E7080 significantly inhibited tumor growth, with a RTV value of 0.81 ± 1.00. E7080 also markedly inhibited metastasis to regional lymph nodes and distant lung. In addition, E7080 reduced angiogenesis and lymphangiogenesis within metastatic nodules in lymph nodes of MDA-MB-231 xenograft models. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: [1] Matsui J, Funahashi Y, Uenaka T, Watanabe T, Tsuruoka A, Asada M. Multi-kinase inhibitor E7080 suppresses lymph node and lung metastases of human mammary breast tumor MDA-MB-231 via inhibition of vascular endothelial growth factor-receptor (VEGF-R) 2 and VEGF-R3 kinase. Clin Cancer Res. 2008 Sep 1; 14 (17): 5459-65. |
|
| Description | Lenvatinib is an inhibitor of multiple RTK with IC50 values of 22 nM, 4 nM, 5.2 nM, 39 nM and 35 nM on VEGFR-1, VEGFR-2, VEGFR-3, PDGFRβ and RET, respectively. | |||||
| Targets | VEGFR-1 | VEGFR-2 | VEGFR-3 | PDGFRβ | RET | |
| IC50 | 22 nM | 4 nM | 5.2 nM | 39 nM | 35 nM | |
Quality Control & MSDS
- View current batch:
Chemical structure
