| CAS |
No.289499-45-2 |
| 中文名称 |
卡奈替尼二盐酸盐 |
| 英文名称 |
Canertinib Dihydrochloride |
| 别名 |
CI-1033dihydrochloride;卡纽替尼二盐酸盐;卡那替尼盐酸盐;卡奈替尼，卡纽替尼;卡纽替尼二盐酸盐卡那替尼; |
| 分子式 |
C24H27Cl3FN5O3 |
| 分子量 |
558.86 |
| 溶解性 |
Soluble in DMSO(Need ultrasonic) |
| 纯度 |
≥98% |
| 外观(性状) |
Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD09954112 |
| SMILES |
C=CC(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)OCCCN4CCOCC4.Cl.Cl |
| InChIKey |
JZZFDCXSFTVOJY-UHFFFAOYSA-N |
| InChI |
InChI=1S/C24H25ClFN5O3.2ClH/c1-2-23(32)30-21-13-17-20(14-22(21)34-9-3-6-31-7-10-33-11-8-31)27-15-28-24(17)29-16-4-5-19(26)18(25)12-16;;/h2，4-5，12-15H，1，3，6-11H2，(H，30，32)(H，27，28，29);2*1H |
| PubChem CID |
156413 |
| 靶点 |
EGFR |
| 通路 |
Angiogenesis;Protein Tyrosine Kinase/RTK |
| 背景说明 |
是有效的，不可逆的 EGFR 抑制剂。 |
| 生物活性 |
Canertinib dihydrochloride (CI-1033 dihydrochloride) is a potent and irreversible EGFR inhibitor; inhibits cellular EGFR and ErbB2 autophosphorylation with IC50s of 7.4 and 9 nM. Canertinib dihydrochloride is active against vaccinia virus respiratory infection in mice.[1-4] |
| In Vitro |
Canertinib dihydrochloride (CI-1033 dihydrochloride) significantly inhibits growth of cultured melanoma cells， RaH3 and RaH5， in a dose-dependent manner. IC50 is approximately 0.8 μM and by 5μM both cell lines are completely growth-arrested within 72 h of treatment. Incubation of exponentially growing RaH3 and RaH5 with 1 μM canertinib accumulated the cells in the G1-phase of the cell cycle within 24 h of treatment without induction of apoptosis. 1 μM canertinib inhibits ErbB1-3 receptor phosphorylation with a concomitant decrease of Akt-， Erk1/2- and Stat3 activity in both cell lines[2].
Canertinib dihydrochloride also is a potent activator of exosome secretion[3]. |
| In Vivo |
Canertinib dihydrochloride (CI-1033 dihydrochloride) shows superior in vivo antitumor activity， giving growth delays in A431 xenografts exceeding 50 days following oral administration[1]. The growth of human malignant melanoma xenografts， RaH3 and RaH5， 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 increased throughout the treatment period as observed through the differences in tumor volumes， reaching statistical significance within 18 days of treatment[2]. |
| 细胞实验 |
RaH3 and RaH5 cells are treated with increasing concentrations (0-10 μM) of Canertinib for 72 h. The cells are suspended in buffer and counted[2]. |
| 动物实验 |
Mice: Canertinib treatment starts when the tumors show reliable growth. The mice are randomized into control and treatment groups. In the canertinib treated RaH3 group (n=4) and RaH5 group (n=7) each mouse receives 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 control RaH3 (n=3) and RaH5 (n=7) mice receive i.p. injections of vehicle only according to the same regimen. At the end of the treatment period， the mice are sacrificed by cervical dislocation where after the tumors are removed and weighed[2]. |
| 激酶实验 |
Enzyme assays for IC50 determinations are performed in 96-well filter plates. The total volume is 0.1 mL containing 20 mM Hepes， pH 7.4， 50 mM sodium vanadate， 40 mM magnesium chloride， 10 μM adenosine triphosphate (ATP) containing 0.5 mCi of [32P]ATP， 20 mg of polyglutamic acid/tyrosine， 10 ng of EGFR tyrosine kinase， and appropriate dilutions of inhibitor (Canertinib). All components except the ATP are added to the well and the plate is incubated with shaking for 10 min at 25°C. The reaction is started by adding [32P]ATP， and the plate is incubated at 25°C for 10 min. The reaction is terminated by addition of 0.1 mL of 20% trichloroacetic acid (TCA). The plate is kept at 4°C for at least 15 min to allow the substrate to precipitate. The wells is then washed five times with 0.2 mL of 10% TCA and 32P incorporation determined with a plate counter[1]. |
| 数据来源文献 |
[1]. Smaill JB， et al. Tyrosine kinase inhibitors. 17. Irreversible inhibitors of the epidermal growth factor receptor: 4-(phenylamino)quinazoline- and 4-(phenylamino)pyrido[3，2-d]pyrimidine-6-acrylamides bearing additional solubilizing functions. J Med Chem.
[2]. Djerf Severinsson EA， et al. The pan-ErbB receptor tyrosine kinase inhibitor canertinib promotes apoptosis of malignant melanoma in vitro and displays anti-tumor activity in vivo. Biochem Biophys Res Commun. 2011 Oct 28;414(3):563-8.
[3]. McAndrews KM， et， al. Mechanisms associated with biogenesis of exosomes in cancer. Mol Cancer. 2019 Mar 30;18(1):52.
[4]. Smee DF， et， al. Progress in the discovery of compounds inhibiting orthopoxviruses in animal models. Antivir Chem Chemother. 2008;19(3):115-24. |
| 规格 |
5mg 10mg 25mg 50mg |
| 单位 |
瓶 |
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