Canertinib dihydrochloride

Category	Orthopoxvirus
CAS	289499-45-2
Description	Canertinib dihydrochloride is the hydrochloride salt of an orally bio-available quinazoline with potential antineoplastic and radiosensitizing activities. Canertinib binds to the intracellular domains of epidermal growth factor receptor tyrosine kinases (ErbB family), irreversibly inhibiting their signal transduction functions and resulting in tumor cell apoptosis and suppression of tumor cell proliferation. This agent also acts as a radiosensitizing agent and displays synergistic activity with other chemotherapeutic agents.

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Product Information

Synonyms	N-(4-((3-Chloro-4-fluorophenyl)amino)-7-(3-(morpholin-4-yl)propoxy)quinazolin-6-yl)prop-2-enamide; CI1033PD183805
IUPAC Name	N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide;dihydrochloride
Molecular Weight	558.86
Molecular Formula	C24H27Cl3FN5O3
Canonical SMILES	C=CC(NC1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C=C1OCCCN4CCOCC4)=O
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)
InChIKey	OMZCMEYTWSXEPZ-UHFFFAOYSA-N
Boiling Point	691ºC at 760mmHg
Flash Point	371.7ºC
Purity	≥98% (HPLC)
Density	1.355g/cm3
Solubility	In Vitro: DMSO : 62.5 mg/mL(111.83 mM;Need ultrasonic) H2O : 25 mg/mL(44.73 mM;Need ultrasonic) In Vivo: 1.Add each solvent one by one:10% DMSO >> 40%PEG300 >> 5%Tween-80 >> 45% saline Solubility: ≥ 2.08 mg/mL (3.72 mM); Clear solution 2.Add each solvent one by one:10% DMSO >> 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.08 mg/mL (3.72 mM); Clear solution 3.Add each solvent one by one:10% DMSO >> 90%corn oil Solubility: 2.08 mg/mL (3.72 mM); Suspended solution; Need ultrasonic
Appearance	Solid powder
Application	Antineoplastic Agents
Storage	Powder: -20°C 3 years 4°C 2 years In solvent: -80°C 6 months -20°C 1 months
Animal Admin	Canertinib treatment begins when tumors show reliable growth. In the canertinib-treated RaH3 group (n = 4) and RaH5 group (n = 7), 1.2 mg of capetinib (40 mg/kg/day) was injected intraperitoneally in 0.1 ml of 0.15 M NaCl 5 days per week for 5 days per week. At the end of the treatment period, mice are sacrificed by cervical dislocation, then tumors are removed and weighed.
Assay	RaH3 and RaH5 cells are treated with Canertinib at increasing concentrations (0-10 μM) for 72 h. Suspend the cells in buffer and count.
Complexity	671
Exact Mass	557.116351
Index Of Refraction	1.649
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. Canertinib also is a potent activator of exosome secretion.
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. 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. 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.
PSA	88.61000
Target	EGFR: 7.4 nM (IC50) ErbB: 9 nM (IC50)
Vapor Pressure	6.08E-19mmHg at 25°C