CHEBI:61399 - canertinib

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ChEBI Name canertinib ChEBI ID CHEBI:61399 Definition A quinazoline compound having a 3-chloro-4-fluoroanilino group at the 4-position, a propenamido group at the 6-position, and a 3-morpholinopropoxy group at the 7-position. Stars This entity has been manually annotated by the ChEBI Team. Supplier Information ChemicalBook:CB01458390, eMolecules:8779390, Selleckchem:CI-1033(Canertinib), ZINC000027439698 Download Molfile XML SDF Find compounds which contain this structure Find compounds which resemble this structure Take structure to the Advanced Search Formula C24H25ClFN5O3 Net Charge 0 Average Mass 485.93800 Monoisotopic Mass 485.16300 InChI 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 SMILES Fc1ccc(Nc2ncnc3cc(OCCCN4CCOCC4)c(NC(=O)C=C)cc23)cc1Cl Roles Classification Biological Role(s): tyrosine kinase inhibitor Any protein kinase inhibitor that interferes with the action of tyrosine kinase. Application(s): antineoplastic agent A substance that inhibits or prevents the proliferation of neoplasms. View more via ChEBI Ontology ChEBI Ontology Outgoing canertinib (CHEBI:61399) has role antineoplastic agent (CHEBI:35610) canertinib (CHEBI:61399) has role tyrosine kinase inhibitor (CHEBI:38637) canertinib (CHEBI:61399) is a monochlorobenzenes (CHEBI:83403) canertinib (CHEBI:61399) is a morpholines (CHEBI:38785) canertinib (CHEBI:61399) is a organofluorine compound (CHEBI:37143) canertinib (CHEBI:61399) is a quinazolines (CHEBI:38530) IUPAC Name N-{4-[(3-chloro-4-fluorophenyl)amino]-7-[3-(morpholin-4-yl)propoxy]quinazolin-6-yl}prop-2-enamide INN Source canertinib ChemIDplus Synonym Source CI-1033 ChEBI Manual Xref Database LSM-1120 LINCS View more database links Registry Number Type Source 267243-28-7 CAS Registry Number ChemIDplus Citations Calvo E, Tolcher AW, Hammond LA, Patnaik A, de Bono JS, Eiseman IA, Olson SC, Lenehan PF, McCreery H, Lorusso P, Rowinsky EK (2004) Administration of CI-1033, an irreversible pan-erbB tyrosine kinase inhibitor, is feasible on a 7-day on, 7-day off schedule: a phase I pharmacokinetic and food effect study. Clinical cancer research : an official journal of the American Association for Cancer Research 10, 7112-7120 [PubMed:15534081] [show Abstract] Purpose To determine the maximum tolerated dose of administrating CI-1033, an oral 4-anilinoquinazoline that irreversibly inhibits the tyrosine kinase domain of all erbB subfamilies, on an intermittent schedule, and assess the interaction of CI-1033 with food on the pharmacokinetic behavior. Experimental design Escalating doses of CI-1033 from a dose level of 300 mg/day for 7 days every other week were administered to patients with advanced solid malignancies. Plasma concentration-time data sets from all evaluable patients were used to develop a population pharmacokinetic model. Noncompartmental methods were used to independently assess the effect of a high-fat meal on CI-1033 absorption and bioavailability. Results Twenty-four patients were treated with 69 twenty-eight day courses. The incidence of unacceptable toxicity, principally diarrhea and skin rash, was observed at the 300 mg/day dose level. At the 250 mg/day level, toxicity was manageable, and protracted administration was feasible. A one-compartment linear model with first-order absorption and elimination adequately described the pharmacokinetic disposition. CL/F, apparent volume of distribution (Vd/F), and ka (mean +/- relative SD) were 280 L/hour +/- 33%, 684 L +/- 20%, and 0.35 hour(-1)+/- 69%, respectively. Cmax values were achieved in 2 to 4 hours. Systemic CI-1033 exposure was largely unaffected by administration of a high-fat meal. At 250 mg, concentration values exceeded IC50 values required for prolonged pan-erbB tyrosine kinase inhibition in preclinical assays. Conclusions The recommended dose on this schedule is 250 mg/day. Its tolerability and the biological relevance of concentrations achieved at the maximal tolerated dose warrant consideration of disease-directed evaluations. This intermittent treatment schedule can be used without regard to meals. Slichenmyer WJ, Elliott WL, Fry DW (2001) CI-1033, a pan-erbB tyrosine kinase inhibitor. Seminars in oncology 28, 80-85 [PubMed:11706399] [show Abstract] Overexpression of the erbB family of receptor tyrosine kinases has been implicated in a variety of tumors including breast, lung, prostate, and brain. Most solid tumors express one or more of these receptors, which can often be related to tumor aggressiveness and poor patient prognosis. CI-1033, a pan-erbB tyrosine kinase inhibitor, is a clinically promising agent that is active against all four members of the erbB receptor tyrosine kinase family. In vitro studies of human cancer cell lines indicate that CI-1033 results in prompt, potent, and sustained inhibition of tyrosine kinase activity. This inhibition is highly selective for erbB1 (epidermal growth factor receptor), erbB2, erbB3, and erbB4 without inhibiting tyrosine kinase activity of receptors such as platelet-derived growth factor receptor, fibroblast growth factor receptor, and insulin receptor, even at high concentrations. Treatment of athymic nude mice bearing xenografts of human A431 epidermoid carcinoma, H125 non-small cell lung carcinoma, and SF-767 glioblastoma results in highly significant suppression of tumor growth. The major toxicity in animals is diarrhea, which is more severe at higher doses. In animal models, all side effects are reversible on cessation of treatment. Thus, CI-1033, which is currently undergoing phase I clinical trials, holds significant potential for use in a broad range of solid tumors. Last Modified 24 February 2016