乐伐替尼作用机制 - Medchemexpress - MCE中国

1、Product Data SheetLenvatinibCat. No.: HY-10981CAS No.: 417716-92-8分式: CHClNO分量: 426.85作靶点: VEGFR; FGFR; PDGFR; c-Kit; RET作通路: Protein Tyrosine Kinase/RTK储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 37.5 mg/mL (87.85 mM; Need ultrasonic)SolventMass1 mg 5 mg 1

2、0 mgConcentration制备储备液1 mM 2.3427 mL 11.7137 mL 23.4274 mL5 mM 0.4685 mL 2.3427 mL 4.6855 mL10 mM 0.2343 mL 1.1714 mL 2.3427 mL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；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vi

3、tro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.86 mM); Clear solution此案可获得 2.5 mg/mL (5.86 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0

4、mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.86 mM); Clear solution此案可获得 2.5 mg/mL (5.86 mM，饱和度未知) 的澄清溶液。Page 1 of 2 www.MedChemE以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄均匀。DMSO 储备液加到 900 L 2

5、0% 的 SBE-CD 理盐溶液中，混合3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.86 mM); Clear solution此案可获得 2.5 mg/mL (5.86 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Lenvatinib (E7080) 种服，多靶点酪氨酸激酶抑制剂，抑制管内长因受体 (VEGFR1-3)，成纤维细胞

6、长因 受体 (FGFR1-4)，板衍长因受体 (PDGFR)，细胞因受体 (KIT)，转染期间重 排 (RET)，显有效抗癌的活性12。IC & Target VEGFR2 VEGFR3 VEGFR1 FGFR14 nM (IC50) 5.2 nM (IC50) 22 nM (IC50) 46 nM (IC50)FGFR2 FGFR3 FGFR4 PDGFR51 nM (IC50)PDGFR c-Kit RET39 nM (IC50) 100 nM (IC50)体外研究 Lenvatinib (E7080) has IC50s of 4, 5.2, 22 nM for VEGFR2 (KDR)

7、, VEGFR3 (Flt-4), and VEGFR1 (Flt-1), respectively.Lenvatinib inhibits PDGFR, PDGFR, FGFR1, and KIT with IC50s of 51, 39, 46, and 100 nM, respectively3.体内研究 Lenvatinib (E7080) (100 mg/kg, p.o.) significantly inhibits local tumor growth at the m.f.p., and at the end oftreatment, Lenvatinib mesylate a

8、lso significantly inhibits metastasis to both regional lymph nodes and distant lung3.Lenvatinib (E7080) inhibits the growth of H146 tumor at 30 and 100 mg/kg (BID, QDx21) in a dose-dependent mannerand causes tumor regression at 100 mg/kg in H146 xenograft model. IHC analysis with anti-CD31 antibody

9、showsthat lenvatinib at 100 mg/kg decreases microvessel density more than anti-VEGF antibody and STI571 treatment4.PROTOCOLCell Assay 1 H146 (1.2103 cells/50 L/well) in SFM containing 0.5% BSA are cultured in 96-well multi-plates. After overnightculture at 37C, SFM (150 L/well) containing 0.5% FBS a

10、nd several concentrations of SCF are added with or withoutseveral concentrations of compound. After culture for 72 hr, the ratios of surviving cells are measured by WST-1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Female BALB/c nude mice (8-

11、12 weeks old, 20-25 g) are maintained under clean-room conditions. H146 tumor cellsAdministration 1 (6.5106) are implanted subcutaneously (s.c.) into the flank region of mice. Twelve days after inoculation, mice arerandomized into control (n=12) and treatment (n=6 or n=5) groups and this point in ti

12、me is identified as day 1.Lenvatinib and STI571, and VEGF neutralization antibody are suspended in 0.5% methylcellulose and saline,respectively, and administered orally twice a day for lenvatinib and STI571 and twice a week for antibody from day 1to day 21. Tumor volume is measured on the indicated

13、days and calculated. Antitumor activity is shown as a relativetumor volume (RTV=calculated tumor volume at indicated days/volume on day 1).MCE has not independently confirmed the accuracy of these methods. They are for reference only.Page 2 of 3 www.MedChemE户使本产品发表的科研献 Sci Transl Med. 2018 Jul 18;10

14、(450). pii: eaaq1093. Acta Pharmacol Sin. 2020 May 12. Exp Cell Res. 2020 May 3:112054. Med Oncol. 2020 Mar 12;37(4):24.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Kudo M, et al. Lenvatinib versus Bay 43-9006 in first-line treatment of patients with unresectable

15、hepatocellularcarcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173.2. Suyama K, et al. Lenvatinib: A Promising Molecular Targeted Agent for Multiple Cancers. Cancer Control. 2018 Jan-Dec;25(1):1073274818789361.3. Matsui J, et al. E7080, a novel inhibitor th

16、at targets multiple kinases, has potent antitumor activities against stem cell factor producing human small celllung cancer H146, based on angiogenesis inhibition. Int J Cancer. 2008, 122(3), 664-671.4. Matsui J, et al. Multi-kinase inhibitor E7080 suppresses lymph node and lung metastases of human mammary breast tumor MDA-MB-231 via inhibitionof vascular endothelial growth factor-receptor (VEGF-R) 2 and VEGF-R3 kinase. Clin Can