| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| 1g |
|
||
| Other Sizes |
|
Purity: ≥98%
Canertinib (formerly also known as CI-1033; CI 1033; PD-183805) is a novel, potent and orally bioavailable quinazoline class of pan-ErbB inhibitor for EGFR and ErbB2 with IC50 of 1.5 nM and 9.0 nM, respectively. It may have anticancer properties, but it doesn't interact with PDGFR, FGFR, InsR, PKC, or CDK1/2/4. When cetinib binds to the intracellular domains of epidermal growth factor receptor tyrosine (ErbB) kinases, it permanently blocks their ability to transmit signals, which causes tumor cells to die off and their growth to be suppressed. In addition to its synergistic effects with other chemotherapeutic agents, this agent also exhibits radiosensitizing properties.
| Targets |
EGFR (IC50 = 7.4 nM); ErbB2 (IC50 = 9 nM)
|
|---|---|
| ln Vitro |
Canertinib significantly inhibits the growth of RaH3 and RaH5 cultured melanoma cells, in a dose-dependent manner. The IC50 is roughly 0.8 μM, and both cell lines completely stop growing at 5μM after 72 hours of treatment. Within 24 hours of treatment, the exponentially growing RaH3 and RaH5 cells were accumulated in the G1-phase of the cell cycle without inducing apoptosis when incubated with 1 μM canertinib. In both cell lines, 1 μM canertinib inhibits ErbB1-3 receptor phosphorylation while concurrently lowering Akt-, Erk1/2-, and Stat3 activity[2].
Moreover, canertinib strongly stimulates exosome secretion[3]. |
| ln Vivo |
Canertinib exhibits enhanced in vivo antitumor activity, causing growth delays in A431 xenografts that last longer than 50 days after oral administration[1]. An intraperitoneal injection of 40 mg/kg/day canertinib significantly inhibits the growth of human malignant melanoma xenografts, RaH3 and RaH5, in nude mice (Fig. 4). Within 4 days of treatment, the anti-proliferative effect on melanoma xenografts is evident. Over the course of the treatment period, this effect is further enhanced as evidenced by differences in tumor volumes, and it reaches statistical significance within 18 days of treatment[2].
|
| 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].
|
| Cell Assay |
For 72 hours, RaH3 and RaH5 cells are exposed to escalating canertinib concentrations (0–10 μM). After being suspended in buffer, the cells are tallied[2].
|
| 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].
|
| References |
| Molecular Formula |
C24H27CL3FN5O3
|
|---|---|
| Molecular Weight |
558.8603
|
| Exact Mass |
557.116351
|
| Elemental Analysis |
C, 51.58; H, 4.87; Cl, 19.03; F, 3.40; N, 12.53; O, 8.59
|
| CAS # |
289499-45-2
|
| Related CAS # |
Canertinib;267243-28-7
|
| Appearance |
Solid powder
|
| SMILES |
C=CC(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)OCCCN4CCOCC4.Cl.Cl
|
| InChi Key |
JZZFDCXSFTVOJY-UHFFFAOYSA-N
|
| InChi Code |
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
|
| Chemical Name |
N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide;dihydrochloride
|
| Synonyms |
CI1033; CI1033; CI-1033; PD183805; PD183805; PD183805; Canertinib HCl; Canertinib dihydrochloride
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 62.5~100 mg/mL (111.8~178.9 mM)
Water: ~33 mg/mL (~59.1 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.72 mM) (saturation unknown) in 10% DMSO + 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 20.8 mg/mL clear DMSO 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: ≥ 2.08 mg/mL (3.72 mM) (saturation unknown) in 10% DMSO + 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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: 2.08 mg/mL (3.72 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Solubility in Formulation 4: 10 mg/mL (17.89 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7894 mL | 8.9468 mL | 17.8936 mL | |
| 5 mM | 0.3579 mL | 1.7894 mL | 3.5787 mL | |
| 10 mM | 0.1789 mL | 0.8947 mL | 1.7894 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.
| In Vitro |
|---|
In vitroactivity: CI-1033 shows excellent potency for irreversible inhibition of erbB2 autophosphorylation in MDA-MB 453 cells. CI-1033 also shows high permeability in Caco-2 cells and inhibits secretory transport of vinblastine, which indicates that CI-1033 is a likely inhibitor of the P-gp. CI-1033 alone, significantly suppresses constitutively activated Akt and MAP kinase. In combination with gemcitabine, CI-1033 inhibits Akt and prevents increased levels of MAPK phosphorylation. CI-1033 stimulates p27 expression and p38 phosphorylation in MDA-MB-453 cells. CI-1033 is highly specific to the erbB receptor family and not sensitive to PGFR, FGFR or IR even at 50 μM. CI-1033 shows high levels of inhibition in A431 cells expressing EGFR with IC50 of 7.4 nM. CI-1033 suppresses heregulin-stimulated tyrosine phosphorylation of erbB2, erbB3 and erbB4 with IC50 of 5, 14 and 10 nM, respectively. CI-1033 also inhibits expression of pp62c-fosin response to heregulin. CI-1033 is predicted to modify Cys773 covalently within the ATP binding site of the HER2 kinase and enhances destruction of both mature and immature ErbB-2 molecules. CI-1033 induces a significant decrease in measurable phosphorylation of tyrosine residues 845 and 1068 of EGFR, which are responsible for Src and Ras/MAPK signaling respectively. The corresponding residues of Her-2, tyrosine residues 877 and 1248 are dephosphorylated significantly by CI-1033 at a concentration of 3 μM or higher. CI could block EGFR internalization and increase the rate of apoptosis in primary osteosarcoma cells in a titratable fashion. In addition, CI-1033 inhibits the proliferation of TT, TE2, TE6 and TE10 cells significantly at 0.1 NM. Kinase Assay: Enzyme assays for determination of IC50 are performed in 96-well filter plates in a total volume of 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 CI-1033. 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 another 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 are then washed five times with 0.2 mL of 10% TCA and 32P incorporation determined with a Wallac β plate counter. Cell Assay: Cells (TT, TE2, TE6 and TE10 cells, 1 × 104) are seeded in each well of a 24-well plastic culture plate and left overnight in DMEM or RPMI-1640 supplemented with 10% FBS. The next morning, the cells are treated with the indicated concentrations of CI-1033 (0.1-5.0 nM) for varying periods (1, 3, 5 and 7 days). After treatment, the cells are counted using a Coulter counter. The percent of cell proliferation is calculated by this formula: treatment cell number/control cell number × 100 for each time period. |
| In Vivo |
|---|
| Animal model |
|---|
| Formulation &Dosage |
|---|
| References |
|---|
J Med Chem.2000 Apr 6;43(7):1380-97;Semin Oncol.2001 Oct;28(5 Suppl 16):80-5. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA