樂伐替尼作用機制 - Medchemexpress - MCE中國

1、Product Data SheetLenvatinibCat. No.: HY-10981CAS No.: 417716-92-8分式: CHClNO分量: 426.85作靶點: VEGFR; FGFR; PDGFR; c-Kit; RET作通路: Protein Tyrosine Kinase/RTK儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 37.5 mg/mL (87.85 mM; Need ultrasonic)SolventMass1 mg 5 mg 1

2、0 mgConcentration制備儲備液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請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時，請在 6 個內(nèi)使，-20C 儲存時，請在 1 個內(nèi)使。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都請先按?In Vi

3、tro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.86 mM); Clear solution此案可獲得 2.5 mg/mL (5.86 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0

4、mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.86 mM); Clear solution此案可獲得 2.5 mg/mL (5.86 mM，飽和度未知) 的澄清溶液。Page 1 of 2 www.MedChemE以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄均勻。DMSO 儲備液加到 900 L 2

5、0% 的 SBE-CD 理鹽溶液中，混合3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.86 mM); Clear solution此案可獲得 2.5 mg/mL (5.86 mM，飽和度未知) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Lenvatinib (E7080) 種服，多靶點酪氨酸激酶抑制劑，抑制管內(nèi)長因受體 (VEGFR1-3)，成纖維細(xì)胞

6、長因 受體 (FGFR1-4)，板衍長因受體 (PDGFR)，細(xì)胞因受體 (KIT)，轉(zhuǎn)染期間重 排 (RET)，顯有效抗癌的活性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)體外研究 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.體內(nèi)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戶使本產(chǎn)品發(fā)表的科研獻 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