CANERTINIB


Synonyms	CI-1033 Canertinib
Status
Molecule Category	Free-form
UNII	C78W1K5ASF
EPA CompTox	DTXSID8048943


Active Pharmaceutical Ingredients Bioactive chemicals	Exact Similarity SubStructure	Threshold (%) >= 70

Structure


InChI Key	OMZCMEYTWSXEPZ-UHFFFAOYSA-N
Smiles	C=CC(=O)Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1
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)

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C24H25ClFN5O3
Molecular Weight	485.95
AlogP	4.39
Hydrogen Bond Acceptor	7.0
Hydrogen Bond Donor	2.0
Number of Rotational Bond	9.0
Polar Surface Area	88.61
Molecular species	NEUTRAL
Aromatic Rings	3.0
Heavy Atoms	34.0

Assay Description	Organism	Bioactivity
Inhibition of A431 cell proliferation	Homo sapiens	0.083 ug.mL-1
Inhibition of EGF-stimulated autophosphorylation of EGFR enzyme in A431 cells detected by immunoblotting	None	7.4 nM
Inhibition of phosphorylation of a polyglutamic acid/tyrosine random copolymer by EGFR enzyme prepared from human A431 carcinoma cell vesicles by immunoaffinity chromatography	None	1.5 nM
Irreversible inhibition of formation of phosphorylated EGFR enzyme in A431 cells 8 hr after washing cells free of the inhibitor	None	80.0 %
Inhibition of autophosphorylation of ERBB2 receptor kinase in MDA-MB 453 cells	None	9.0 nM
Inhibition of Epidermal Growth Factor Receptor (EGFR) autophosphorylation	Homo sapiens	74.0 nM
Inhibition of human epidermal growth factor receptor-2 autophosphorylation	Homo sapiens	529.0 nM
Inhibition of SW-620 cell proliferation	Homo sapiens	1.45 ug.mL-1
Inhibition of SKBR-3 cell proliferation	Homo sapiens	0.102 ug.mL-1
Average Binding Constant for BTK; NA=Not Active at 10 uM	Homo sapiens	750.0 nM
Average Binding Constant for EPHA6; NA=Not Active at 10 uM	Homo sapiens	72.0 nM
Average Binding Constant for SLK; NA=Not Active at 10 uM	Homo sapiens	440.0 nM
Average Binding Constant for EPHA4; NA=Not Active at 10 uM	Homo sapiens	310.0 nM
Average Binding Constant for EPHA5; NA=Not Active at 10 uM	Homo sapiens	270.0 nM
Average Binding Constant for EPHA8; NA=Not Active at 10 uM	Homo sapiens	790.0 nM
Average Binding Constant for EPHA3; NA=Not Active at 10 uM	Homo sapiens	650.0 nM
Average Binding Constant for STK10; NA=Not Active at 10 uM	Homo sapiens	430.0 nM
Average Binding Constant for RIPK2; NA=Not Active at 10 uM	Homo sapiens	330.0 nM
Average Binding Constant for GAK; NA=Not Active at 10 uM	Homo sapiens	44.0 nM
Average Binding Constant for LYN; NA=Not Active at 10 uM	Homo sapiens	780.0 nM
Average Binding Constant for LCK; NA=Not Active at 10 uM	Homo sapiens	560.0 nM
Average Binding Constant for ERBB2; NA=Not Active at 10 uM	Homo sapiens	8.4 nM
Average Binding Constant for EGFR; NA=Not Active at 10 uM	Homo sapiens	1.4 nM
Average Binding Constant for ABL1; NA=Not Active at 10 uM	Homo sapiens	340.0 nM
Average Binding Constant for ABL1(Q252H); NA=Not Active at 10 uM	Homo sapiens	470.0 nM
Average Binding Constant for ABL1(H396P); NA=Not Active at 10 uM	Homo sapiens	320.0 nM
Average Binding Constant for ABL1(M351T); NA=Not Active at 10 uM	Homo sapiens	560.0 nM
Average Binding Constant for ABL1(T315I); NA=Not Active at 10 uM	Homo sapiens	290.0 nM
Average Binding Constant for ABL1(Y253F); NA=Not Active at 10 uM	Homo sapiens	420.0 nM
Average Binding Constant for SRC; NA=Not Active at 10 uM	Homo sapiens	760.0 nM
Inhibition of EGFR	None	2.3 nM
Inhibition of HER2	None	48.0 nM
Inhibition of HER4	None	14.0 nM
Inhibition of Blk	None	50.0 nM
Inhibition of Bmx	None	586.0 nM
Inhibition of Btk	None	185.0 nM
Inhibition of Blk expressed in mouse BAF3 cells assessed as cytotoxicity	None	29.0 nM
Inhibition of Bmx expressed in mouse BAF3 cells assessed as cytotoxicity	None	62.0 nM
Inhibition of EGFR by HTRF assay	None	5.0 nM
Inhibition of ERBb2 by HTRF assay	None	80.0 nM
Antiproliferative activity against human HN5 cells overexpressing EGFR after 3 days by methylene blue staining	Homo sapiens	50.0 nM
Antiproliferative activity against human BT474 cells overexpressing ERBb2 after 3 days by methylene blue staining	Homo sapiens	10.0 nM
Binding constant for ABL1(H396P) kinase domain	Homo sapiens	500.0 nM
Binding constant for EGFR kinase domain	Homo sapiens	0.19 nM
Binding constant for EGFR(G719C) kinase domain	Homo sapiens	0.13 nM
Binding constant for RET(M918T) kinase domain	Homo sapiens	840.0 nM
Binding constant for DDR1 kinase domain	Homo sapiens	400.0 nM
Binding constant for EGFR(G719S) kinase domain	Homo sapiens	0.19 nM
Binding constant for FLT3(D835Y) kinase domain	Homo sapiens	730.0 nM
Binding constant for TXK kinase domain	Homo sapiens	700.0 nM
Binding constant for ABL1(M351T) kinase domain	Homo sapiens	640.0 nM
Binding constant for ABL1(Q252H) kinase domain	Homo sapiens	200.0 nM
Binding constant for EGFR(L858R) kinase domain	Homo sapiens	0.24 nM
Binding constant for BLK kinase domain	Homo sapiens	45.0 nM
Binding constant for EGFR(L747-E749del, A750P) kinase domain	Homo sapiens	0.17 nM
Binding constant for EGFR(L747-S752del, P753S) kinase domain	Homo sapiens	0.26 nM
Binding constant for full-length MKNK1	Homo sapiens	260.0 nM
Binding constant for JAK3(Kin.Dom.2/JH1 - catalytic) kinase domain	Homo sapiens	630.0 nM
Binding constant for LCK kinase domain	Homo sapiens	320.0 nM
Binding constant for TGFBR2 kinase domain	Homo sapiens	800.0 nM
Binding constant for ABL1(Y253F) kinase domain	Homo sapiens	730.0 nM
Binding constant for ABL2 kinase domain	Homo sapiens	870.0 nM
Binding constant for EGFR(E746-A750del) kinase domain	Homo sapiens	0.26 nM
Binding constant for EGFR(S752-I759del) kinase domain	Homo sapiens	0.19 nM
Binding constant for ERBB2 kinase domain	Homo sapiens	87.0 nM
Binding constant for ERBB4 kinase domain	Homo sapiens	29.0 nM
Binding constant for LYN kinase domain	Homo sapiens	810.0 nM
Binding constant for GAK kinase domain	Homo sapiens	100.0 nM
Binding constant for ABL1(T315I) kinase domain	Homo sapiens	550.0 nM
Binding constant for EGFR(L747-T751del,Sins) kinase domain	Homo sapiens	0.26 nM
Binding constant for EGFR(L861Q) kinase domain	Homo sapiens	0.22 nM
Binding constant for RIPK2 kinase domain	Homo sapiens	300.0 nM
Binding constant for EPHA6 kinase domain	Homo sapiens	270.0 nM
Binding constant for MEK5 kinase domain	None	60.0 nM
Binding constant for MKK7 kinase domain	None	110.0 nM
Binding constant for LRRK2 kinase domain	None	500.0 nM
Binding constant for EPHA6 kinase domain	None	270.0 nM
Binding constant for QSK kinase domain	None	700.0 nM
Binding constant for JAK3(JH1domain-catalytic) kinase domain	None	630.0 nM
Binding constant for KIT(A829P) kinase domain	None	700.0 nM
Binding constant for KIT(D816H) kinase domain	None	600.0 nM
Binding constant for MET(Y1235D) kinase domain	None	830.0 nM
Binding constant for ERBB2 kinase domain	None	56.0 nM
Binding constant for ERBB4 kinase domain	None	6.5 nM
Binding constant for MKNK1 kinase domain	None	260.0 nM
Binding constant for IRAK1 kinase domain	None	450.0 nM
Binding constant for BLK kinase domain	None	45.0 nM
Binding constant for CSNK1E kinase domain	None	420.0 nM
Binding constant for DDR1 kinase domain	None	400.0 nM
Binding constant for ERBB3 kinase domain	None	210.0 nM
Binding constant for LYN kinase domain	None	810.0 nM
Binding constant for TGFBR2 kinase domain	None	800.0 nM
Binding constant for TXK kinase domain	None	700.0 nM
Binding constant for RIPK2 kinase domain	None	300.0 nM
Binding constant for FLT3(D835Y) kinase domain	None	730.0 nM
Binding constant for FLT3(R834Q) kinase domain	None	490.0 nM
Binding constant for EPHB6 kinase domain	None	640.0 nM
Binding constant for MAP4K2 kinase domain	None	330.0 nM
Binding constant for ABL1(E255K)-phosphorylated kinase domain	None	30.0 nM
Binding constant for ABL1(F317L)-phosphorylated kinase domain	None	91.0 nM
Binding constant for ABL1(H396P)-non phosphorylated kinase domain	None	46.0 nM
Binding constant for ABL1(H396P)-phosphorylated kinase domain	None	57.0 nM
Binding constant for ABL1(M351T)-phosphorylated kinase domain	None	38.0 nM
Binding constant for ABL1(Q252H)-non phosphorylated kinase domain	None	91.0 nM
Binding constant for ABL1(Q252H)-phosphorylated kinase domain	None	22.0 nM
Binding constant for ABL1(T315I)-non phosphorylated kinase domain	None	690.0 nM
Binding constant for ABL1(T315I)-phosphorylated kinase domain	None	69.0 nM
Binding constant for ABL1(Y253F)-phosphorylated kinase domain	None	42.0 nM
Binding constant for ABL1-non phosphorylated kinase domain	None	210.0 nM
Binding constant for ABL1-phosphorylated kinase domain	None	30.0 nM
Binding constant for ABL2 kinase domain	None	870.0 nM
Binding constant for EGFR kinase domain	None	0.19 nM
Binding constant for EGFR(E746-A750del) kinase domain	None	0.26 nM
Binding constant for EGFR(G719C) kinase domain	None	0.13 nM
Binding constant for EGFR(G719S) kinase domain	None	0.19 nM
Binding constant for EGFR(L747-E749del, A750P) kinase domain	None	0.17 nM
Binding constant for EGFR(L747-S752del, P753S) kinase domain	None	0.26 nM
Binding constant for EGFR(L747-T751del,Sins) kinase domain	None	0.26 nM
Binding constant for EGFR(L858R) kinase domain	None	0.24 nM
Binding constant for EGFR(L858R,T790M) kinase domain	None	0.28 nM
Binding constant for EGFR(L861Q) kinase domain	None	0.22 nM
Binding constant for EGFR(S752-I759del) kinase domain	None	0.19 nM
Binding constant for EGFR(T790M) kinase domain	None	0.1 nM
Binding constant for GAK kinase domain	None	100.0 nM
Binding constant for LCK kinase domain	None	320.0 nM
Binding constant for RET(M918T) kinase domain	None	840.0 nM
Binding constant for YSK4 kinase domain	None	700.0 nM
Antiproliferative activity against human HCC827 cells harboring EGFR del E746-A750 mutant after 72 hrs by MTS assay	Homo sapiens	1.0 nM
Antiproliferative activity against human NCI-H1975 cells harboring EGFR L858R/T790M mutant after 72 hrs by MTS assay	Homo sapiens	64.0 nM
Antiproliferative activity against human A431 cells overexpressing EGFR after 72 hrs by MTS assay	Homo sapiens	150.0 nM
Inhibition of EGFR	None	1.5 nM
Inhibition of ErbB2	None	5.0 nM
Inhibition of ErbB4	None	10.0 nM
Inhibition of epidermal growth factor receptor kinase (unknown origin) using [33P]-ATP after 20 to 30 mins by radiometric assay	Homo sapiens	0.8 nM
Reversible binding affinity to human EGFR L858R/ T790M double mutant expressed in baculovirus by fluorometric analysis	Homo sapiens	0.11 nM
Inhibition of EGF-stimulated wild type EGFR autophosphorylation expressed in human A549 cells by sandwich ELISA	Homo sapiens	6.0 nM
Inhibition of EGFR L858R/T790M double mutant autophosphorylation in human NCI-H1975 cells after 2 hrs by sandwich ELISA	Homo sapiens	3.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	Homo sapiens	687.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	Homo sapiens	504.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	Homo sapiens	8.0 nM
Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	Homo sapiens	679.0 nM
Inhibition of EGFR (unknown origin)	Homo sapiens	7.4 nM
Antiproliferative activity against human NCI-H1975 cells expressing EGFR T790M/L858R mutant incubated for 72 hrs by MTS assay	Homo sapiens	101.0 nM
Inhibition of GST-tagged human EGFR catalytic domain expressed in insect cells	Homo sapiens	0.3 nM
Inhibition of GST-tagged human HER2 catalytic domain expressed in insect cells	Homo sapiens	30.0 nM
Inhibition of human EGFR T790M/L858R mutant expressed in mouse Ba/F3 cells	Homo sapiens	26.0 nM
Inhibition of human EGFR L858R mutant expressed in mouse Ba/F3 cells	Homo sapiens	0.4 nM
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging	Homo sapiens	3.21 %
Inhibition of human A431 cell-derived EGFR using polyglutamic acid/tyrosine as substrate incubated for 10 mins followed by [32P]ATP addition and measured after 10 mins by beta counting method	Homo sapiens	15.0 nM
Inhibition of EGFR (unknown origin)	Homo sapiens	2.0 nM
Inhibition of EGFR (unknown origin) assessed as reduction of phosphorylation of polyglutamic acid/tyrosine incubated for 10 mins by beta scintillation counter	Homo sapiens	0.8 nM
Inhibition of HER2 (unknown origin) assessed as reduction of phosphorylation of polyglutamic acid/tyrosine incubated for 10 mins by beta scintillation counter	Homo sapiens	19.0 nM
Inhibition of probe binding to EGFR L858R mutant (unknown origin) using rabbit reticulate lysate system after 1 hr by luminescence assay	Homo sapiens	2.7 nM
Antiproliferative activity against human UCH1 cells measured after 72 hrs by alamar blue assay	Homo sapiens	80.0 nM
Binding affinity to wild-type human partial length EGFR (R669 to V1011 residues) expressed in bacterial expression system by Kinomescan method	Homo sapiens	0.19 nM
Binding affinity to wild-type human partial length GAK (G13 to Y338 residues) expressed in bacterial expression system by Kinomescan method	Homo sapiens	100.0 nM
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	19.67 %	SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	-67.61 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging	Chlorocebus sabaeus	0.22 %	Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging	Chlorocebus sabaeus	-0.23 %	Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging	Chlorocebus sabaeus	0.22 %	Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging	Chlorocebus sabaeus	-0.23 %
Inhibition of recombinant human N-terminal GST tagged EGFR L858R/T790M double mutant (669 to 1210 residues) expressed in insect expression system using peptide as substrate incubated for 2 hrs followed by substrate addition and measured after 30 mins by TR-FRET assay	Homo sapiens	1.26 nM
Inhibition of recombinant human N-terminal GST tagged EGFR d746-750 mutant (669 to 1210 residues) expressed in insect expression system using peptide as substrate incubated for 2 hrs followed by substrate addition and measured after 30 mins by TR-FRET assay	Homo sapiens	0.04 nM
Inhibition of recombinant human N-terminal GST tagged EGFR L858R mutant (669 to 1210 residues) expressed in insect expression system using peptide as substrate incubated for 2 hrs followed by substrate addition and measured after 30 mins by TR-FRET assay	Homo sapiens	0.1 nM
Antiproliferative activity against human PC-9 cells assessed as inhibition of cell growth measured after 72 hrs by CCK-8 assay	Homo sapiens	0.8585 nM
Antiproliferative activity against human PB1 cells assessed as inhibition of cell growth measured after 72 hrs by CCK-8 assay	Homo sapiens	70.19 nM
Antiproliferative activity against human NCI-H1975 cells assessed as inhibition of cell growth measured after 72 hrs by CCK-8 assay	Homo sapiens	11.34 nM
Antiproliferative activity against human HCC827 cells assessed as inhibition of cell growth measured after 72 hrs by CCK-8 assay	Homo sapiens	0.3776 nM
Antiproliferative activity against mouse BaF3 cells assessed as inhibition of cell growth measured after 72 hrs by CCK-8 assay	Mus musculus	9.2 nM

Related Entries

Cross References

Resources	Reference
ChEBI	61399
ChEMBL	CHEMBL31965
DrugBank	DB05424
FDA SRS	C78W1K5ASF
Guide to Pharmacology	5675
PubChem	156414
SureChEMBL	SCHEMBL54837
ZINC	ZINC000027439698

CONTENTS