Icotinib-Hydrochloride-BPI-2009H-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEIcotinib HydrochlorideCat. No.: HY-15164CAS No.: 1204313-51-8Synonyms: BPI-2009H分式: CHClNO分量: 427.88作靶点: EGFR作通路: JAK/STAT Signaling; Protein Tyrosine Kinase/RTK储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 mo

2、nth溶解性数据体外实验 DMSO : 25 mg/mL (58.43 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.3371 mL 11.6855 mL 23.3710 mL5 mM 0.4674 mL 2.3371 mL 4.6742 mL10 mM 0.2337 mL 1.1686 mL 2.3371 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，并请注意储备液的保存式和期限。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，配制前请先配制澄清的储备液，再依次添加助溶剂(

3、为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.84 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.84 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO

4、90% corn oil1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (5.84 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Icotinib Hydrochloride (BPI-2009)是有效，选择性的 EGFR 抑制剂，IC50 值为5 nM；也抑制突变型EGFRL858R，EGFRL858R/T790M，EGFRT790M 和 EGFRL861Q。IC50 & Target EGFR EGFRL861Q EGFRL858R/T790M EGFRL85

5、8R5 nM (IC50)EGFRT790M体外研究 Incubation with Iconitib at 0.5 M results in kinase activity inhibition of 91%, 99%, 96%, 61% and 61%,respectively. Iconitib inhibits the proliferation of A431 and BGC-823 A549, H460 and KB cell lines with IC50sof 1, 4.06, 12.16, 16.08, 40.71 M. When profiled with 88 kinas

6、es, Icotinib only shows meaningful inhibitoryactivity to EGFR and its mutants. Icotinib blocks EGFR-mediated intracellular tyrosine phosphorylation(IC50=45 nM) in the human epidermoid carcinoma A431 cell line and inhibits tumor cell proliferation 1.体内研究 Icotinib exhibits potent dose-dependent antitu

7、mor effects in nude mice carrying a variety of human tumor-derived xenografts. The drug is well tolerated at doses up to 120 mg/kg/day in mice without mortality orsignificant body weight loss during the treatment. Icotinib inhibits tumor growth at a rate of 25.2%, 45.6% and51.5% in the A431 cell lin

8、e groups; 3.4%, 25.9% and 31.0% in the A549 cell line groups; 49.4%, 52.6% and67.4% in the H460 cell line groups, and 30.3%, 36.4% and 46.5% in the HCT8 cell line groups, at 30, 60 and120 mg/kg/dose, respectively 1.PROTOCOLKinase Assay 1 In the in vitro kinase assays, 2.4 ng/L EGFR protein is mixed

9、with 32 ng/L Crk in 25 L kinase reactionbuffer containing 1 M cold ATP and 1 Ci32P-ATP. The mix is incubated with Icotinib at 0, 0.5, 2.5, 12.5or 62.5 nM on ice for 10 min followed by incubation at 30C for 20 min. After quenching with SDS samplebuffer at 100C for 4 min, the protein mix is resolved b

10、y electrophoresis in a 10% SDSgel. The driedgel is then exposed to detect radioactivity. Quantification is performed by software 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Cells (1000/well) are seeded into 96-well plates in RPMI-1640

11、 medium containing 10% FBS and grown in a5% CO2 incubator at 37C. After 24 h, cells are treated with Icotinib at 0, 0.78, 1.56, 3.125, 6.25, 12.5 or 25 M for 96 h. Cell proliferation is calculated by subtracting the mean absorbance value on day 0 from the meanabsorbance value on day 4 1.MCE has not

12、independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: The effect of three doses of Icotinib (30, 60, and 120 mg/kg/dose p.o. qd) on antitumor activity andAdministration 1 survival is determined in mice bearing A431, A549, H460 and HCT8 tumor xenografts. Taxo

13、l (30 mg/kg/dosei.p. once a week) is employed in these experiments as a positive control group 1.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEMCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Science. 2017 Dec 1;358(6367). Sci Transl Med.

14、2018 Jul 18;10(450). pii: eaaq1093. Biochem Pharmacol. 2016 Dec 1;121:67-77. Eur J Pharmacol. 2019 May 5;850:141-149.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Tan F, et al. Icotinib (BPI-2009H), a novel EGFR tyrosine kinase inhibitor, displays potent efficacy in preclinical studies. Lung Cancer.2012 May;76(