Canertinib (CI-1033)是一种强效、不可逆的EGFR抑制剂，对EGFR、HER2和HER4的IC50值分别为0.8、19和7nM。
Cas No.:267243-28-7
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
Canertinib (CI-1033) is a potent and irreversible EGFR inhibitor that inhibits EGFR, HER2, and HER4 with IC50 values of 0.8, 19, and 7nM, respectively [1]. Canertinib decreases the phosphorylation of an ErbB kinase signaling target p70S6-kinase T389, as well as the inactivation of downstream signaling molecules [2]. Canertinib has been widely used to inhibit tumor growth and induce ototoxicity in different preclinical models [3].
In vitro, Canertinib treatment for 72 hours significantly inhibited the proliferation of RaH3 cells and RaH5 cells, with IC50 values of 0.78μM and 0.80μM, respectively[4]. Canertinib treatment at 2μM for 72 hours significantly induced G1 phase cell cycle arrest and promoted cell apoptosis in HL-60 cells[5]. Canertinib treatment at 10μM for 6h significantly inhibited Akt and Erk1/2 phosphorylation and promoted PARP cleavage in Jurkat cells[6].
In vivo, Canertinib treatment via intraperitoneal injection at a dose of 80mg/kg/day for 4 days induced regression of FDC-P1/FLT3-ITD cells injected intravenously in transplanted mice[7]. Oral administration of Canertinib at a dose of 5mg/kg/day for 6 weeks significantly inhibited tumor growth in xenograft mice injected with CD63-BCAR4-overexpressing cells[8].
References:
[1] Ayati A, Moghimi S, Salarinejad S, et al. A review on progression of epidermal growth factor receptor (EGFR) inhibitors as an efficient approach in cancer targeted therapy[J]. Bioorganic chemistry, 2020, 99: 103811.
[2] Hojjat-Farsangi M. Small-molecule inhibitors of the receptor tyrosine kinases: promising tools for targeted cancer therapies[J]. International journal of molecular sciences, 2014, 15(8): 13768-13801.
[3] Tang J, Qian Y, Li H, et al. Canertinib induces ototoxicity in three preclinical models[J]. Hearing research, 2015, 328: 59-66.
[4] Severinsson E A D, Trinks C, Gréen H, et al. The pan-ErbB receptor tyrosine kinase inhibitor canertinib promotes apoptosis of malignant melanoma in vitro and displays anti-tumor activity in vivo[J]. Biochemical and Biophysical Research Communications, 2011, 414(3): 563-568.
[5] Trinks C, Djerf E A, Hallbeck A L, et al. The pan-ErbB receptor tyrosine kinase inhibitor canertinib induces ErbB-independent apoptosis in human leukemia (HL-60 and U-937) cells[J]. Biochemical and biophysical research communications, 2010, 393(1): 6-10.
[6] Trinks C, Severinsson E A, Holmlund B, et al. The pan-ErbB tyrosine kinase inhibitor canertinib induces caspase-mediated cell death in human T-cell leukemia (Jurkat) cells[J]. Biochemical and biophysical research communications, 2011, 410(3): 422-427.
[7] Nordigården A, Zetterblad J, Trinks C, et al. Irreversible pan‐ERBB inhibitor canertinib elicits anti‐leukaemic effects and induces the regression of FLT3‐ITD transformed cells in mice[J]. British journal of haematology, 2011, 155(2): 198-208.
[8] Bae K, Kim J H, Lee J Y, et al. Oncogenic fusion of BCAR4 activates EGFR signaling and is sensitive to dual inhibition of EGFR/HER2[J]. Frontiers in Molecular Biosciences, 2022, 9: 952651.
Canertinib (CI-1033)是一种强效、不可逆的EGFR抑制剂，对EGFR、HER2和HER4的IC50值分别为0.8、19和7nM[1]。Canertinib可降低ErbB激酶信号靶点p70S6激酶T389的磷酸化，并使下游信号分子失活[2]。Canertinib已被广泛用于不同临床前模型中抑制肿瘤生长并诱导耳毒性[3]。
在体外，Canertinib处理72小时显著抑制了RaH3细胞和RaH5细胞的增殖，IC50值分别为0.78µM和0.80µM[4]。使用2µM的Canertinib处理72小时，显著诱导了HL-60细胞发生G1期细胞周期阻滞并促进了细胞凋亡[5]。使用10µM的Canertinib处理6小时，显著抑制了Jurkat细胞中Akt和Erk1/2的磷酸化，并促进了PARP的裂解[6]。
在体内，每日腹腔注射80mg/kg剂量的Canertinib，持续4天，诱导了移植小鼠中静脉注射的FDC-P1/FLT3-ITD细胞消退[7]。每日口服5mg/kg剂量的Canertinib，持续6周，显著抑制了注射过表达CD63-BCAR4细胞的异种移植小鼠中的肿瘤生长[8]。
| Cell experiment [1]: | |
Cell lines | HL-60 cells |
Preparation Method | HL-60 cells were cultured in RPMI 1640 supplemented with 10% heat-killed fetal bovine serum (FCS), 2mM L-glutamine, penicillin (50U/ml), and streptomycin (50μg/ml) in a humidified atmosphere of 5% CO2 at 37°C. HL-60 cells were seeded in 35 mm dishes at a concentration of 0.2 × 106 cells /ml and treated with different concentrations of Canertinib (0, 2, 4, 6, 8, and 10µM) for 72h. Cell viability was then analyzed. |
Reaction Conditions | 0, 2, 4, 6, 8, and 10µM; 72h |
Applications | Canertinib treatment decreased the cell viability of HL-60 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | DBA/2 mice |
Preparation Method | DBA/2 mice (12-week-old) were housed in well-ventilated cages and had access to diet and water ad libitum. Environmental conditions in the feeding chamber were controlled with a temperature of 23.5±2°C, humidity of 60±12%, and a 12h light/dark cycle. FDC-P1 cells (2×106) transduced with retrovirus expressing FLT3-ITD and enhanced yellow fluorescence protein (EYFP) were injected into the tail vein of syngenic DBA/2 mice in 0.2ml phosphate-buffered saline (PBS) per mouse. Seven days later, the level of engraftment was analyzed by flow cytometry on peripheral blood samples collected by lateral-tail vein bleeding. Treatment was initiated on day 9 by intraperitoneal injections of 0.5ml of Canertinib (80mg/kg/day) in PBS and continued for four consecutive days (day 10-13). On day 14, the experiment was terminated, and a new blood sample was taken to determine the engraftment after treatment. |
Dosage form | 80mg/kg/day for 4 days; i.p. |
Applications | Canertinib treatment induced regression of intravenously injected FLT3-ITD cells in mice. |
References: | |
| Cas No. | 267243-28-7 | SDF | |
| 别名 | 卡奈替尼; CI-1033; PD-183805 | ||
| 化学名 | N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide | ||
| Canonical SMILES | C=CC(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)OCCCN4CCOCC4 | ||
| 分子式 | C24H25ClFN5O3 | 分子量 | 485.94 |
| 溶解度 | ≥ 12.15mg/mL in DMSO with gentle warming | 储存条件 | Store at -20°C |
| General tips | 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；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.0579 mL | 10.2893 mL | 20.5787 mL |
| 5 mM | 411.6 μL | 2.0579 mL | 4.1157 mL |
| 10 mM | 205.8 μL | 1.0289 mL | 2.0579 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet