Lucitanib-E-3810-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemELucitanibCat. No.: HY-15391CAS No.: 1058137-23-7Synonyms: E-3810分式: CHNO分量: 443.49作靶點(diǎn): VEGFR; FGFR作通路: Protein Tyrosine Kinase/RTK儲(chǔ)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(shí)驗(yàn) DMSO : 25 mg/mL (5

2、6.37 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.2548 mL 11.2742 mL 22.5484 mL5 mM 0.4510 mL 2.2548 mL 4.5097 mL10 mM 0.2255 mL 1.1274 mL 2.2548 mL請(qǐng)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(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前?qǐng)先配制澄清的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的

3、可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.64 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.64 mM); Clear solution1/3 Master of Small Molecules 您

4、邊的抑制劑師www.MedChemE3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.64 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Lucitanib (E-3810)是VEGFR 和 FGFR 的雙重 抑制劑，有效和選擇性地抑制VEGFR1，VEGFR2，VEGFR3，F(xiàn)GFR1，F(xiàn)GFR2，IC50分別為7 nM，25 nM，10 nM，17.5 nM，82.5 nM。IC50 & Target VEGFR1 VEGFR2 VEGFR3 FGFR17 nM (IC50) 25

5、nM (IC50) 10 nM (IC50) 17.5 nM (IC50)FGFR282.5 nM (IC50)體外研究 Consistent with the inhibitory activity of VEGFR and FGFR auto-phosphorylation, Lucitanib potently inhibitsVEGF and bFGF-stimulated HUVEC proliferation with IC50 of 40 and 50 nM, respectively. Besides, Lucitanib(E-3810) also inhibits CSF-1

6、R with IC50 of 5 nM 1. Lucitanib potently inhibits FGFR2 activity (Kii=0.11 M).The Ki values obtained for DDR2, LYN, CARDIAK, CSBP (2), EPHA2, and YES range between 0.26 and 8 M 2.體內(nèi)研究 Lucitanib (E-3810), at oral dosing of 20 mg/kg for 7 consecutive days, completely inhibits (P 1. The activityof Luc

7、itanib (E-3810) given at the doses of 15 mg/kg is tested on MDA-MB-231 breast cancer transplantedsubcutaneously, at a late stage, when tumor masses reach 350 to 400 mg. This tumor xenograft is verysensitive to Lucitanib (E-3810), with complete tumor stabilization lasting throughout the 30-day treatm

8、ent. Asin other tumor models, tumors re-grow after withdrawal of Lucitanib (E-3810) at a rate similar to controltumors 3.PROTOCOLCell Assay 1 Exponentially growing HUVEC or NHI3T3 cells are seeded into 96-well plates at a density of 3 to 6103cells/100 L/well in complete medium. In the experiments wi

9、thout serum starvation, 24 hours after seeding,cells are exposed to different Lucitanib (E-3810) concentrations without or with VEGF165 (50 ng/mL) orbFGF (20 ng/mL) ligands and the antiproliferative effect of the drugs is evaluated after 72 hours by MTSColorimetric Assay. In the assays with serum st

10、arvation conditions, 24 hours after seeding complete mediumis removed and after 3 rounds of washing with PBS, cells are cultured in medium containing 1% BSA. After18 to 24 hours, cells are processed. Exponentially growing A2780, A498, SN12KI, and HepG2 cells areseeded into 96-well plates at 3 to 510

11、3 cells/100 L/well in complete medium. Twenty-four hours later cellsare treated with different drug concentrations for 72 hours and the antiproliferative effect is evaluated by MTS1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 32/3 Master

12、 of Small Molecules 您邊的抑制劑師www.MedChemEAdministration 2 MDA-MB-231 tumor-bearing mice are randomized when their tumor masses are about 350 to 400 mg toreceive Lucitanib (E-3810) (15 mg/kg), Brivanib, and Sunitinib at the doses used for the antitumor activitytrial, for 10 days. Four hours after the a

13、ntiangiogenic dose of day 7, Paclitaxel is injected intravenously at thedose of 20 mg/kg and tumor and plasma samples are collected after 1, 4, and 24 hours in all the groups(each group consisting of 3 animals). At the indicated sampling time, mice are anesthetized, blood iscollected from the retro-

14、orbital plexus into heparinized tubes, and the plasma fraction is separated. Mice arekilled by cervical dislocation, and tumors excised and snap-frozen. The samples are analyzed by high-performance liquid chromatography (HPLC) with UV detection at 230 nm.MCE has not independently confirmed the accur

15、acy of these methods. They are for reference only.戶(hù)使本產(chǎn)品發(fā)表的科研獻(xiàn) Science. 2017 Dec 1;358(6367). Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Bello E, et al. E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitu

16、mor activity in multiple preclinical models. CancerRes. 2011 Feb 15;71(4):1396-405.2. Colzani M, et al. Quantitative chemical proteomics identifies novel targets of the anti-cancer multi-kinase inhibitor E-3810. Mol CellProteomics. 2014 Jun;13(6):1495-509.3. Bello E, et al. The tyrosine kinase inhibitor E-3810 combined with paclitaxel inhibits the growth of advanced-stage triple-negative breastcancer xeno