| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
Canertinib (formerly CI-1033; CI1033; PD183805; PD-183805) is an irreversible/covalent, quinazoline-based and orally bioavailable pan-ErbB inhibitor for EGFR and ErbB2 with potential antineoplastic activity. With IC50s of 1.5 nM and 9.0 nM, respectively, it inhibits EGFR and ErbB2, but it is inert against PDGFR, FGFR, InsR, PKC, and CDK1/2/4. Inducing tumor cell apoptosis and suppressing tumor cell proliferation, canertinib binds to the intracellular domains of epidermal growth factor receptor tyrosine (ErbB) kinases, irreversibly inhibiting their signal transduction functions. In addition, this agent exhibits synergistic activity with other chemotherapeutic agents and functions as a radiosensitizing agent.
| Targets |
EGFR (IC50 = 7.4 nM); ErbB2 (IC50 = 9 nM)
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|---|---|
| ln Vitro |
Canertinib significantly inhibits the growth of RaH3 and RaH5 cultured melanoma cells, in a dose-dependent manner. After 72 hours of treatment, both cell lines completely stop growing at 5μM, with an IC50 of about 0.8 μM. When 1 μM canertinib was added to exponentially growing RaH3 and RaH5, the cells accumulated in the G1-phase of the cell cycle within 24 hours of treatment, without causing apoptosis. In both cell lines, 1 μM canertinib inhibits the phosphorylation of the ErbB1-3 receptor while concurrently lowering the activity of Akt, Erk1/2, and Stat3.
Canertinib also is a potent exosome secretion activator[3]. |
| ln Vivo |
Canertinib exhibits better in vivo antitumor activity, causing growth delays in A431 xenografts that last longer than 50 days after oral administration[1]. Intraperitoneal injections of 40 mg/kg/day canertinib significantly inhibit the growth of human malignant melanoma xenografts, RaH3 and RaH5, in nude mice (Fig. 4). Observed through differences in tumor volumes, the anti-proliferative effect on melanoma xenografts is evident as early as day 4 of treatment and continues to increase over the course of the course of treatment, reaching statistical significance within 18 days of treatment[2].
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| Enzyme Assay |
In 96-well filter plates, enzyme assays are carried out to determine IC50. 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 suitable dilutions of inhibitor (Canertinib) are all included in the 0.1 mL total volume. All ingredients are added to the well, with the exception of the ATP, and the plate is shaken for 10 minutes at 25°C. After adding [32P]ATP, the plate is incubated for 10 minutes at 25°C to initiate the reaction. The addition of 0.1 mL of 20% trichloroacetic acid (TCA) stops the reaction. To enable the substrate to precipitate, the plate is maintained at 4°C for a minimum of 15 minutes. After that, 0.2 mL of 10% TCA and 32P incorporation measured with a plate counter are used to wash the wells five times[1].
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| Cell Assay |
Canertinib is applied to RaH3 and RaH5 cells at escalating concentrations (0–10 μM) for a duration of 72 hours. The cells are counted after being suspended in buffer[2].
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| Animal Protocol |
Mice: Treatment with canertinib begins when tumors exhibit consistent growth. Groups for treatment and control are randomly assigned to the mice. Every mouse in the canertinib-treated RaH3 group (n = 4) and RaH5 group (n = 7) gets intraperitoneal injections five days a week of 1.2 mg canertinib (40 mg/kg/day) in 0.1 ml 0.15 M NaCl. The same regimen is followed for the intraperitoneal injection of vehicle only in the control RaH3 (n = 3) and RaH5 (n = 7) mice. The mice are sacrificed by cervical dislocation at the conclusion of the treatment period, following the removal and weighing of the tumors[2].
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| References |
| Molecular Formula |
C24H25CLFN5O3
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|---|---|
| Molecular Weight |
485.94
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| Exact Mass |
485.16
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| Elemental Analysis |
C, 59.32; H, 5.19; Cl, 7.30; F, 3.91; N, 14.41; O, 9.88
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| CAS # |
267243-28-7
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| Related CAS # |
Canertinib dihydrochloride;289499-45-2
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| Appearance |
Solid powder
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| SMILES |
C=CC(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)OCCCN4CCOCC4
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| InChi Key |
OMZCMEYTWSXEPZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H25ClFN5O3/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)
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| Chemical Name |
N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide
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| Synonyms |
Canertinib; Canertinib free base; PD-183805; CI1033; CI1 033; CI-1033; PD 183805; PD183805
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.57 mM) (saturation unknown) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear EtOH stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.25 mg/mL (2.57 mM) (saturation unknown) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear EtOH stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1.25 mg/mL (2.57 mM) (saturation unknown) in 10% EtOH + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 30% propylene glycol, 5% Tween 80, 65% D5W: 10mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0579 mL | 10.2893 mL | 20.5787 mL | |
| 5 mM | 0.4116 mL | 2.0579 mL | 4.1157 mL | |
| 10 mM | 0.2058 mL | 1.0289 mL | 2.0579 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00050830 | Completed | Drug: CI 1033 | Lung Neoplasms | Pfizer | January 2003 | Phase 2 |
| NCT00051051 | Completed | Drug: CI-1033 | Breast Neoplasms | Pfizer | December 2002 | Phase 2 |
| NCT00174356 | Completed | Drug: CI 1033 Drug: PACLITAXEL |
Carcinoma, Non-Small Cell Lung | Pfizer | December 2002 | Phase 1 |
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