Canertinib

Summary

Canertinib (CHEMBL31965) is a phase-3 clinical-stage small-molecule tyrosine kinase inhibitor targeting EGFR and ERBB2; with CIViC clinical evidence for 3 variant-indication associations (e.g. EGFR L858R in lung non-small cell carcinoma).

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 2 (EGFR, ERBB2)
• Clinical trials: 1
• Precision-oncology evidence (CIViC): 3 variant–indication associations
• Chemistry: 485.9 Da · C24H25ClFN5O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL31965
Name	Canertinib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	156414
ChEBI	CHEBI:61399
Molecular formula	C24H25ClFN5O3
Molecular weight	485.9
InChIKey	OMZCMEYTWSXEPZ-UHFFFAOYSA-N

SMILES: C=CC(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)OCCCN4CCOCC4

IUPAC name: N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide

ChEBI 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.

Pharmacological roles (ChEBI): tyrosine kinase inhibitor, antineoplastic agent.

Also known as: Canertinib, CANERTINIB, PD-0183805, PD-183805, CI-1033, SN-26606, CANERTINIB (CI-1033), CANERTINIB DIHYDROCHLORIDE, GW781483X, PD183805, SID124894124, SID144206912

Parent form; salt/anhydrous children: CHEMBL545315

Patent coverage: 2,873 distinct patent families (8,083 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 7,760 (96%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
EGFR	epidermal growth factor receptor	Inhibition	8.82	17.5%	P00533
ERBB2	erb-b2 receptor tyrosine kinase 2	Inhibition	8.05	17.7%	P04626

Broader ChEMBL bioactivity targets: 110 (assay-derived). Sample: Leucine-rich repeat serine/threonine-protein kinase 2, Homeodomain-interacting protein kinase 4, Hormonally up-regulated neu tumor-associated kinase, Receptor-interacting serine/threonine-protein kinase 3, Receptor tyrosine-protein kinase erbB-2, Tyrosine-protein kinase Fyn, Tyrosine-protein kinase ABL1, Vascular endothelial growth factor receptor 1, Platelet-derived growth factor receptor beta, Mast/stem cell growth factor receptor Kit.

Bioactivity

ChEMBL activities: 361 potent at pChembl ≥ 5 of 362 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
EGFR	10.4	IC50	0.04	nM	CHEMBL_ACT_22844198
EGFR	10	IC50	0.1	nM	CHEMBL_ACT_22844222
EGFR	10	Kd	0.1	nM	CHEMBL_ACT_7595723
EGFR	9.96	Ki	0.11	nM	CHEMBL_ACT_16540034
EGFR	9.89	Kd	0.13	nM	CHEMBL_ACT_2898741
EGFR	9.89	Kd	0.13	nM	CHEMBL_ACT_7595714
EGFR	9.77	Kd	0.17	nM	CHEMBL_ACT_2898817
EGFR	9.77	Kd	0.17	nM	CHEMBL_ACT_7595716
EGFR	9.72	Kd	0.19	nM	CHEMBL_ACT_19218713
EGFR	9.72	Kd	0.19	nM	CHEMBL_ACT_2898665
EGFR	9.72	Kd	0.19	nM	CHEMBL_ACT_2898779
EGFR	9.72	Kd	0.19	nM	CHEMBL_ACT_2904753
EGFR	9.72	Kd	0.19	nM	CHEMBL_ACT_7595712
EGFR	9.72	Kd	0.19	nM	CHEMBL_ACT_7595715
EGFR	9.72	Kd	0.19	nM	CHEMBL_ACT_7595722
EGFR	9.66	Kd	0.22	nM	CHEMBL_ACT_2904715
EGFR	9.66	Kd	0.22	nM	CHEMBL_ACT_7595721
EGFR	9.62	Kd	0.24	nM	CHEMBL_ACT_2898931
EGFR	9.62	Kd	0.24	nM	CHEMBL_ACT_7595719
EGFR	9.59	Kd	0.26	nM	CHEMBL_ACT_2898703
EGFR	9.59	Kd	0.26	nM	CHEMBL_ACT_2898855
EGFR	9.59	Kd	0.26	nM	CHEMBL_ACT_2898893
EGFR	9.59	Kd	0.26	nM	CHEMBL_ACT_7595713
EGFR	9.59	Kd	0.26	nM	CHEMBL_ACT_7595717
EGFR	9.59	Kd	0.26	nM	CHEMBL_ACT_7595718
EGFR	9.55	Kd	0.28	nM	CHEMBL_ACT_7595720
EGFR	9.52	IC50	0.3	nM	CHEMBL_ACT_18784590
EGFR	9.52	IC50	0.3	nM	CHEMBL_ACT_26212427
EGFR	9.4	IC50	0.4	nM	CHEMBL_ACT_18784603
EGFR	9.4	IC50	0.4	nM	CHEMBL_ACT_26212431

Target pathways

Aggregated over 2 target gene(s): EGFR, ERBB2.

Top Reactome pathways

53 total, by targets touching each:

Pathway	Targets	Genes
Signaling by ERBB2	2	EGFR, ERBB2
SHC1 events in ERBB2 signaling	2	EGFR, ERBB2
PLCG1 events in ERBB2 signaling	2	EGFR, ERBB2
PIP3 activates AKT signaling	2	EGFR, ERBB2
GRB2 events in ERBB2 signaling	2	EGFR, ERBB2
PI3K events in ERBB2 signaling	2	EGFR, ERBB2
Constitutive Signaling by Aberrant PI3K in Cancer	2	EGFR, ERBB2
RAF/MAP kinase cascade	2	EGFR, ERBB2
ERBB2 Regulates Cell Motility	2	EGFR, ERBB2
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	2	EGFR, ERBB2
ERBB2 Activates PTK6 Signaling	2	EGFR, ERBB2
Downregulation of ERBB2 signaling	2	EGFR, ERBB2
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	2	EGFR, ERBB2
Signaling by ERBB2 KD Mutants	2	EGFR, ERBB2
Signaling by ERBB2 ECD mutants	2	EGFR, ERBB2
Signaling by ERBB2 TMD/JMD mutants	2	EGFR, ERBB2
Developmental Lineage of Mammary Gland Myoepithelial Cells	2	EGFR, ERBB2
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	1	EGFR
Signaling by ERBB4	1	EGFR
GRB7 events in ERBB2 signaling	1	ERBB2
Downregulation of ERBB2:ERBB3 signaling	1	ERBB2
Signaling by EGFR	1	EGFR
GRB2 events in EGFR signaling	1	EGFR
GAB1 signalosome	1	EGFR
SHC1 events in EGFR signaling	1	EGFR
EGFR downregulation	1	EGFR
EGFR interacts with phospholipase C-gamma	1	EGFR
EGFR Transactivation by Gastrin	1	EGFR
Sema4D induced cell migration and growth-cone collapse	1	ERBB2
Signal transduction by L1	1	EGFR

Dominant GO biological processes

GO term	Targets
signal transduction	2
cell surface receptor signaling pathway	2
epidermal growth factor receptor signaling pathway	2
neuron differentiation	2
positive regulation of cell growth	2
ERBB2-EGFR signaling pathway	2
negative regulation of apoptotic process	2
positive regulation of MAPK cascade	2
phosphatidylinositol 3-kinase/protein kinase B signal transduction	2
positive regulation of epithelial cell proliferation	2
cellular response to epidermal growth factor stimulus	2
protein phosphorylation	2
cell surface receptor protein tyrosine kinase signaling pathway	2
cell population proliferation	2
regulation of cell population proliferation	2

Indications & clinical

Indications

0 indications (0 at ChEMBL trial phase 4).

Clinical trials

Total trials: 1.

Phase distribution

Phase	Trials
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00051051	PHASE2	COMPLETED	A Phase II Study of CI-1033 in Treating Patients With Metastatic (Stage IV) Breast Cancer

Clinical evidence (CIViC)

Variant × indication × effect (3 predictive associations from 3 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
EGFR L858R	Lung Non-small Cell Carcinoma	Sensitivity/Response	Canertinib	CIViC D	EID2631
EGFR T790M	Lung Non-small Cell Carcinoma	Sensitivity/Response	Canertinib	CIViC D	EID2165
ERBB2 L755S	Breast Cancer	Sensitivity/Response	Canertinib	CIViC D	EID10022

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

171 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
AFATINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
DACOMITINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
GEFITINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
LAPATINIB DITOSYLATE	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
LAZERTINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
MOBOCERTINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
SELUMETINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
ACALABRUTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
AFATINIB DIMALEATE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
BITHIONOL	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
BOSUTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
BRIGATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
CABOZANTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
COLISTIN	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
DASATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
EBASTINE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
ECONAZOLE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
ERLOTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
HEXACHLOROPHENE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
IBRUTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
IMATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
LAPATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
MICONAZOLE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
MITOXANTRONE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
NERATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
OSIMERTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
PONATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
SORAFENIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
TAMOXIFEN	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
TRIBROMSALAN	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
TUCATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
VANDETANIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
ZANUBRUTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
ALISERTIB	ChEMBL	Phase 3	EGFR, ERBB2
ALVOCIDIB	ChEMBL	Phase 3	EGFR, ERBB2
CANDESARTAN	ChEMBL	Phase 3	EGFR, ERBB2
CEDIRANIB	ChEMBL	Phase 3	EGFR, ERBB2
ENCLOMIPHENE	ChEMBL	Phase 3	EGFR, ERBB2
MASITINIB	ChEMBL	Phase 3	EGFR, ERBB2
POZIOTINIB	ChEMBL	Phase 3	EGFR, ERBB2
PYROTINIB	ChEMBL	Phase 3	EGFR, ERBB2
REMIBRUTINIB	ChEMBL	Phase 3	EGFR, ERBB2
ZONGERTINIB	ChEMBL	Phase 3	EGFR, ERBB2
AEE-788	ChEMBL	Phase 2	EGFR, ERBB2
ALLITINIB	ChEMBL	Phase 2	EGFR, ERBB2
ATUZABRUTINIB	ChEMBL	Phase 2	EGFR, ERBB2
CENISERTIB	ChEMBL	Phase 2	EGFR, ERBB2
CLOSANTEL	ChEMBL	Phase 2	EGFR, ERBB2
CP-724714	ChEMBL	Phase 2	EGFR, ERBB2
DEFOSBARASERTIB	ChEMBL	Phase 2	EGFR, ERBB2
ELLAGIC ACID	ChEMBL	Phase 2	EGFR, ERBB2
FALNIDAMOL	ChEMBL	Phase 2	EGFR, ERBB2
FORETINIB	ChEMBL	Phase 2	EGFR, ERBB2
ILORASERTIB	ChEMBL	Phase 2	EGFR, ERBB2
IODOQUINOL	ChEMBL	Phase 2	EGFR, ERBB2