Canertinib-dihydrochloride-CI-1033-dihydrochloride-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECanertinib dihydrochlorideCat. No.: HY-10367ACAS No.: 289499-45-2Synonyms: CI-1033 dihydrochloride; PD-183805 dihydrochloride分式: CHClFNO分量: 558.86作靶点: EGFR作通路: JAK/STAT Signaling; Protein Tyrosine Kinase/RTK储存式: Powder -20C 3 ye

2、ars4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 155 mg/mL (277.35 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.7894 mL 8.9468 mL 17.8936 mL5 mM 0.3579 mL 1.7894 mL 3.5787 mL10 mM 0.1789 mL 0.8947 mL 1.7894 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂

3、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(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: 2.58 mg/mL (4.62 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in salin

4、e)Solubility: 2.58 mg/mL (4.62 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 Canertinib dihydrochloride (CI-1033;PD-183805)是有效地，不可逆的 EGFR 抑制剂；抑制细胞 EGFR 和ErbB2 磷酸化的 IC50 值分别为7.4和9 nM。IC50 & Target EGFR ErbB27.4 nM (IC50) 9 nM (IC50)体外研究 Canertinib signific

5、antly inhibits growth of cultured melanoma cells, RaH3 and RaH5, in a dose-dependentmanner. IC50 is approximately 0.8 M and by 5M both cell lines are completely growth-arrested within 72 hof treatment. Incubation of exponentially growing RaH3 and RaH5 with 1 M canertinib accumulated the cellsin the

6、G1-phase of the cell cycle within 24 h of treatment without induction of apoptosis. 1 M canertinibinhibits ErbB1-3 receptor phosphorylation with a concomitant decrease of Akt-, Erk1/2- and Stat3 activity inboth cell lines 2.体内研究 Canertinib shows superior in vivo antitumor activity, giving growth del

7、ays in A431 xenografts exceeding 50days following oral administration 1. The growth of human malignant melanoma xenografts, RaH3 andRaH5, in nude mice is significantly inhibited by i.p. injections of 40 mg/kg/day canertinib (Fig. 4). The anti-proliferative effect on melanoma xenografts is visible al

8、ready within 4 days of treatment and further increasedthroughout the treatment period as observed through the differences in tumor volumes, reaching statisticalsignificance within 18 days of treatment 2.PROTOCOLKinase Assay 1 Enzyme assays for IC50 determinations are performed in 96-well filter plat

9、es. The total volume is 0.1 mLcontaining 20 mM Hepes, pH 7.4, 50 mM sodium vanadate, 40 mM magnesium chloride, 10 M adenosinetriphosphate (ATP) containing 0.5 mCi of 32PATP, 20 mg of polyglutamic acid/tyrosine, 10 ng of EGFRtyrosine kinase, and appropriate dilutions of inhibitor (Canertinib). All co

10、mponents except the ATP are addedto the well and the plate is incubated with shaking for 10 min at 25C. The reaction is started by adding32PATP, and the plate is incubated at 25C for 10 min. The reaction is terminated by addition of 0.1 mL of20% trichloroacetic acid (TCA). The plate is kept at 4C fo

11、r at least 15 min to allow the substrate toprecipitate. The wells is then washed five times with 0.2 mL of 10% TCA and 32P incorporation determinedwith a plate counter 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 2 RaH3 and RaH5 cells ar

12、e treated with increasing concentrations (0-10 M) of Canertinib for 72 h. The cellsare suspended in buffer and counted 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: Canertinib treatment starts when the tumors show reliable growth. The m

13、ice are randomized intoAdministration 2 control and treatment groups. In the canertinib treated RaH3 group (n=4) and RaH5 group (n=7) each mousereceives i.p. injections of 1.2 mg canertinib (40 mg/kg/day) in 0.1 ml 0.15 M NaCl 5 days a week. The controlRaH3 (n=3) and RaH5 (n=7) mice receive i.p. inj

14、ections of vehicle only according to the same regimen. At2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEthe end of the treatment period, the mice are sacrificed by cervical dislocation where after the tumors areremoved and weighed 2.MCE has not independently confirmed the accuracy of these methods

15、. They are for reference only.户使本产品发表的科研献 Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. J Cell Sci. 2015 Sep 1;128(17):3317-29. J Biol Chem. 2012 Mar 23;287(13):9742-52. Biochemistry. 2018 Feb 27;57(8):1369-1379. Biochemistry. 2017 Jun 13;56(23):2921-2927.See more customer validations on HYPER

16、LINK / www.MedChemEREFERENCES1. Smaill JB, et al. Tyrosine kinase inhibitors. 17. Irreversible inhibitors of the epidermal growth factor receptor: 4-(phenylamino)quinazoline- and 4-(phenylamino)pyrido3,2-dpyrimidine-6-acrylamides bearing additional solubilizing functions. J Med Chem.2000 Apr 6;43(7):1380-97.2. Djerf Severinsson EA, et al. The pan-ErbB receptor tyrosine kinase inhibitor canertinib promotes apoptosis of malignant melanoma invitro and displays anti-tumor activity in vivo. Bio