Canertinib-CI-1033-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECanertinibCat. No.: HY-10367CAS No.: 267243-28-7Synonyms: CI-1033; PD-183805分式: CHClFNO分量: 485.94作靶點(diǎn): EGFR作通路: JAK/STAT Signaling; Protein Tyrosine Kinase/RTK儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month

2、溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 4.9 mg/mL (10.08 mM; Need warming)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.0579 mL 10.2893 mL 20.5787 mL5 mM 0.4116 mL 2.0579 mL 4.1157 mL10 mM 0.2058 mL 1.0289 mL 2.0579 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，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Canertinib (CI-1033;PD-183805)有

3、效地，不可逆的 EGFR 抑制劑；抑制細(xì)胞 EGFR 和 ErbB2 磷酸化的IC50 值分別為7.4和9 nM。IC50 & Target EGFR ErbB27.4 nM (IC50) 9 nM (IC50)1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE體外研究 Canertinib significantly inhibits growth of cultured melanoma cells, RaH3 and RaH5, in a dose-dependentmanner. IC50 is approximately 0.8 M a

4、nd 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 G1-phase of the cell cycle within 24 h of treatment without induction of apoptosis. 1 M canertinibinhibits ErbB1-3 recept

5、or phosphorylation with a concomitant decrease of Akt-, Erk1/2- and Stat3 activity inboth cell lines 2.體內(nèi)研究 Canertinib shows superior in vivo antitumor activity, giving growth delays in A431 xenografts exceeding 50days following oral administration 1. The growth of human malignant melanoma xenograft

6、s, 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 already within 4 days of treatment and further increasedthroughout the treatment period as observed through the differences

7、 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 plates. The total volume is 0.1 mLcontaining 20 mM Hepes, pH 7.4, 50 mM sodium vanadate, 40 mM magnesium chloride, 10 M adeno

8、sinetriphosphate (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 components except the ATP are addedto the well and the plate is incubated with shaking for 10 min at 25C. The reaction is s

9、tarted 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 for at least 15 min to allow the substrate toprecipitate. The wells is then washed five times with 0.2 mL of 10% TCA and 32

10、P 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 are treated with increasing concentrations (0-10 M) of Canertinib for 72 h. The cellsare suspended in buffer and counted 2.

11、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 mice are randomized intoAdministration 2 control and treatment groups. In the canertinib treated RaH3 group (n=4) and RaH5

12、 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. injections of vehicle only according to the same regimen. Atthe end of the treatment period, the mice are sacrificed by cerv

13、ical dislocation where after the tumors areremoved and weighed 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. J Cell Sci. 2015 Sep 1;128(17):3317-29.2/3 Master of Small Molecules 您邊的抑制劑師

14、www.MedChemE 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 HYPERLINK / www.MedChemEREFERENCES1. Smaill JB, et al. Tyrosine kinase inhibitors. 17. Irreversible inhibitors of the epiderma

15、l 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. Biochem Biophys Res Comm