Icotinib

Summary

Icotinib (CHEMBL2087361) is a phase-3 clinical-stage small molecule (ATC L01EB08) targeting EGFR; indicated across 13 conditions including neoplasm and non-small cell lung carcinoma; with CIViC clinical evidence for 4 variant-indication associations (e.g. EGFR L858R in lung adenocarcinoma).

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• ATC class: L01EB08
• Targets: 1 (EGFR)
• Indications: 13 conditions
• Clinical trials: 70
• Precision-oncology evidence (CIViC): 4 variant–indication associations
• Chemistry: 391.4 Da · C22H21N3O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2087361
Name	Icotinib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	22024915
ATC	L01EB08
Molecular formula	C22H21N3O4
Molecular weight	391.4
InChIKey	QQLKULDARVNMAL-UHFFFAOYSA-N

SMILES: C#CC1=CC(=CC=C1)NC2=NC=NC3=CC4=C(C=C32)OCCOCCOCCO4

IUPAC name: N-(3-ethynylphenyl)-2,5,8,11-tetraoxa-15,17-diazatricyclo[10.8.0.014,19]icosa-1(12),13,15,17,19-pentaen-18-amine

Also known as: Bpi-2009, Icotinib, ICOTINIB

Parent form; salt/anhydrous children: CHEMBL4297665

Patent coverage: 1,217 distinct patent families (2,802 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 2,721 (97%) 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	7.35	17.5%	P00533

Broader ChEMBL bioactivity targets: 9 (assay-derived). Sample: Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma, Mitotic checkpoint serine/threonine-protein kinase BUB1, Epidermal growth factor receptor, Mitogen-activated protein kinase kinase kinase 1, Serine/threonine-protein kinase 10, Cysteine–tRNA ligase, cytoplasmic, STE20-like serine/threonine-protein kinase, Cyclin-G-associated kinase, Receptor-interacting serine/threonine-protein kinase 2.

Bioactivity

ChEMBL activities: 15 potent at pChembl ≥ 5 of 16 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
EGFR	8.91	IC50	1.23	nM	CHEMBL_ACT_26838745
EGFR	8.91	IC50	1.23	nM	CHEMBL_ACT_27322259
EGFR	8.7	IC50	2	nM	CHEMBL_ACT_11022075
EGFR	8.7	IC50	2.02	nM	CHEMBL_ACT_26838736
EGFR	8.7	IC50	2.02	nM	CHEMBL_ACT_27322250
EGFR	8.3	IC50	5	nM	CHEMBL_ACT_18997561
EGFR	7.35	IC50	45	nM	CHEMBL_ACT_11022086
STK10	6.64	Kd	227	nM	CHEMBL_ACT_17940635
CARS1	6.19	Kd	652	nM	CHEMBL_ACT_17887506
GAK	6.14	Kd	725	nM	CHEMBL_ACT_17904232
SLK	5.98	Kd	1051	nM	CHEMBL_ACT_17939200
RIPK2	5.58	Kd	2627	nM	CHEMBL_ACT_17935470
BUB1	5.54	Kd	2912	nM	CHEMBL_ACT_17886241
MAP3K1	5.38	Kd	4131	nM	CHEMBL_ACT_17911591
PIP4K2C	5.33	Kd	4663	nM	CHEMBL_ACT_17926843

Target pathways

Aggregated over 1 target gene(s): EGFR.

Top Reactome pathways

37 total, by targets touching each:

Pathway	Targets	Genes
Signaling by ERBB2	1	EGFR
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	1	EGFR
Signaling by ERBB4	1	EGFR
SHC1 events in ERBB2 signaling	1	EGFR
PLCG1 events in ERBB2 signaling	1	EGFR
PIP3 activates AKT signaling	1	EGFR
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
GRB2 events in ERBB2 signaling	1	EGFR
PI3K events in ERBB2 signaling	1	EGFR
EGFR interacts with phospholipase C-gamma	1	EGFR
EGFR Transactivation by Gastrin	1	EGFR
Constitutive Signaling by Aberrant PI3K in Cancer	1	EGFR
Signal transduction by L1	1	EGFR
Constitutive Signaling by EGFRvIII	1	EGFR
Inhibition of Signaling by Overexpressed EGFR	1	EGFR
RAF/MAP kinase cascade	1	EGFR
ERBB2 Regulates Cell Motility	1	EGFR
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	EGFR
ERBB2 Activates PTK6 Signaling	1	EGFR
Cargo recognition for clathrin-mediated endocytosis	1	EGFR
Clathrin-mediated endocytosis	1	EGFR
PTK6 promotes HIF1A stabilization	1	EGFR
Downregulation of ERBB2 signaling	1	EGFR
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	1	EGFR
Extra-nuclear estrogen signaling	1	EGFR
NOTCH3 Activation and Transmission of Signal to the Nucleus	1	EGFR

Dominant GO biological processes

GO term	Targets
cell morphogenesis	1
ossification	1
embryonic placenta development	1
positive regulation of protein phosphorylation	1
hair follicle development	1
ubiquitin-dependent protein catabolic process	1
signal transduction	1
cell surface receptor signaling pathway	1
epidermal growth factor receptor signaling pathway	1
salivary gland morphogenesis	1
learning or memory	1
positive regulation of cell population proliferation	1
gene expression	1
protein ubiquitination	1
cerebral cortex cell migration	1

Indications & clinical

Indications

13 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
neoplasm	3	MONDO:0005070	EFO:0000616
non-small cell lung carcinoma	3	MONDO:0005233	EFO:0003060
lung neoplasm	3	MONDO:0021117	MONDO:0008903
carcinoma	2	MONDO:0004993	EFO:0000313
lung adenocarcinoma	2	MONDO:0005061	EFO:0000571
psoriasis	2	MONDO:0005083	EFO:0000676
squamous cell lung carcinoma	2	MONDO:0005097	EFO:0000708
esophageal squamous cell carcinoma	2	MONDO:0005580	EFO:0005922
bronchial neoplasm	2	MONDO:0002807	EFO:1000849
breast neoplasm	2	MONDO:0021100	MONDO:0007254
nasopharyngeal carcinoma	2	MONDO:0015459	MONDO:0015459
exocrine pancreatic carcinoma	1	MONDO:0005192	EFO:0002618

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 70.

Phase distribution

Phase	Trials
PHASE2	39
PHASE3	13
PHASE4	9
PHASE1	3
Not specified	3
PHASE1/PHASE2	2
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01465243	PHASE4	COMPLETED	Dose Escalation Of Icotinib In Previously Treated Patients With Routine Dose
NCT01646450	PHASE4	UNKNOWN	First-line Treatment With Icotinib in Elder NSCLC EGFR Mutated Patients
NCT01720901	PHASE4	SUSPENDED	Increased Dose of Icotinib in Advanced None Small Cell Lung Cancer Patients After Routine Gefitinib Therapy
NCT02031601	PHASE4	UNKNOWN	Intercalated Combination of Chemotherapy and Tyrosine Kinase Inhibitors as First-line Treatment for Patients With Non-Small-Cell Lung Cancer
NCT02103257	PHASE4	UNKNOWN	Sequential Icotinib Plus Chemotherapy Versus Icotinib Alone as First-line Treatment in Stage IIIB/IV Lung Adenocarcinoma
NCT02194556	PHASE4	UNKNOWN	Sequential and Maintenance Icotinib Plus Chemotherapy Versus Icotinib Maintenance After Chemotherapy in Advanced NSCLC
NCT02283424	PHASE4	UNKNOWN	Icotinib as the Adjunctive Treatment After Surgery in Stage I-IIIB Lung Adenocarcinoma Patients With EGFR Gene Mutation
NCT02404675	PHASE4	UNKNOWN	High Dose Icotinib in Advanced Non-small Cell Lung Cancer With EGFR 21 Exon Mutation
NCT02744664	PHASE4	COMPLETED	Cryotherapy Combine Icotinib for Advanced NSCLC Treatment
NCT06041776	PHASE3	RECRUITING	Adjuvant Befotertinib in Stage IB-IIIB Non-small Cell Lung Cancer With Positive EGFR Sensitive Mutations
NCT06955325	PHASE3	NOT_YET_RECRUITING	Umbrella Trial of Adjuvant Therapy in Completely Resected High-risk Stage IA-IB NSCLC: Focus on Driver Mutations
NCT01040780	PHASE3	COMPLETED	Safety and Efficacy Study of Icotinb in Non-small Cell Lung Cancer (NSCLC) Patients
NCT01719536	PHASE3	COMPLETED	Icotinib Versus First-line Chemotherapy Plus Maintenance Treatment in EGFR Positive Lung Adenocarcinoma Patients
NCT01724801	PHASE3	COMPLETED	Icotinib or Whole Brain Irradiation in EGFR-mutant Lung Cancer
NCT01996098	PHASE3	TERMINATED	Icotinib Following Chemotherapy Versus Chemotherapy as Adjuvant Therapy in Stage IIA-IIIA NSCLC With EGFR Mutation
NCT02125240	PHASE3	UNKNOWN	Icotinib Versus Placebo as Adjuvant Therapy in EGFR-mutant Lung Adenocarcinoma
NCT02448797	PHASE3	UNKNOWN	Icotinib as Adjuvant Therapy Compared With Standard Chemotherapy in Stage II-IIIA NSCLC With EGFR-mutation
NCT02486354	PHASE3	COMPLETED	Icotinib in Advanced Metastatic Patients With NSCLC Previously Treated With Chemotherapy
NCT02883543	PHASE3	UNKNOWN	First-line Icotinib With Concurrent Radiotherapy for NSCLC With EGFR Mutation
NCT03992885	PHASE3	UNKNOWN	Clinical Study of Combination Therapy With Ectiecinib, Pemetrexed and Platinum in Patients With Metastatic Non-squamous Non-small Cell Lung Cancer With EGFR Mutations.
NCT04058704	PHASE3	UNKNOWN	A Study to Determine the Efficiency For Brain Metastasis NSCLC Patients Treated With Icotinib Alone or Combined With Radiation Therapy
NCT04797806	PHASE3	UNKNOWN	Study of Anlotinib Combined With Icotinib as the First-line Treatment in Patients With EGFR Concomitant Mutation NSCLC
NCT05007938	PHASE2	ACTIVE_NOT_RECRUITING	Befotertinib and Icotinib in Treatment-naive Patients With Advanced EGFR-Mutant Lung Cancer
NCT05104788	PHASE2	RECRUITING	A Study of Icotinib With Chemotherapy as Neoadjuvant Therapy for Patients With EGFRm Positive Resectable Non-Small Cell Lung Cancer
NCT05132985	PHASE2	NOT_YET_RECRUITING	Neoadjuvant Icotinib With Chemotherapy for Epidermal Growth Factor Receptor(EGFR)-Mutated Resectable Lung Adenocarcinoma
NCT06517953	PHASE2	RECRUITING	Befotertinib and Icotinib for NSCLC With Uncommon EGFR Mutations
NCT01514877	PHASE2	COMPLETED	Icotinib Combined With Whole Brain Radiotherapy in Treating Multiple Brain Metastases From Non-Small Cell Lung Cancer
NCT01516983	PHASE1/PHASE2	COMPLETED	Icotinib Combined With WBRT For NSCLC Patients With Brain Metastases and EGFR Mutation
NCT01534585	PHASE1/PHASE2	COMPLETED	Safety and Efficacy Study of Icotinib With Intensity-modulated Radiotherapy in Nasopharyngeal Carcinoma
NCT01688713	PHASE2	UNKNOWN	Phase II Trial of Double Dose of Icotinib in Treating Brain Metastases From Non-small Cell Lung Cancer
NCT01707329	PHASE2	UNKNOWN	Icotinib in Combination With Chemotherapy Versus Chemotherapy Alone in Patients Progressed After Icotinib Treatment
NCT01843647	PHASE2	UNKNOWN	Neoadjuvant Therapy of Icotinib in Epidermal Growth Factor Receptor Mutated NSCLC Patients
NCT01855854	PHASE2	COMPLETED	Second-line Treatment With Icotinib in Esophageal Carcinoma Patients With EGFR Overexpression (IHC 3+) or Positive FISH
NCT01929200	PHASE2	UNKNOWN	Icotinib as Adjuvant Therapy in Treating Non-small-cell Lung Cancer Patients With Positive EGFR Mutation
NCT01963195	PHASE2	UNKNOWN	Evaluation of the High Dose of Icotinib in Advanced Lung Cancer Patients After Failure of Target Therapy
NCT02009605	PHASE2	UNKNOWN	Icotinib in Previously Treated Non/Light-smoking Patients With Advanced Squamous Cell Lung Cancer
NCT02044328	PHASE2	COMPLETED	Icotinib as an Adjuvant Therapy for Patients With Stage IIA-IIIA Adenocarcinoma With EGFR Mutation
NCT02062515	PHASE2	UNKNOWN	Icotinib in Advanced Non-small Cell Lung Cancer (NSCLC) With Hepatic Insufficiency
NCT02191059	PHASE2	UNKNOWN	Phase II Clinical Study of Intermittent High Dose of Icotinib in Combination With Docetaxel to Treat Lung Cancer
NCT02264210	PHASE2	COMPLETED	Icotinib for Completed Resected IB NSCLC With EGFR Mutation

Clinical evidence (CIViC)

Variant × indication × effect (4 predictive associations from 4 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
EGFR L858R	Lung Adenocarcinoma	Sensitivity/Response	Icotinib	CIViC C	EID12548
EGFR::RAD51 Fusion	Lung Adenocarcinoma	Sensitivity/Response	Icotinib	CIViC C	EID7314
EGFR::SEPTIN14 Fusion	Lung Adenocarcinoma	Sensitivity/Response	Carboplatin + Paclitaxel Liposome + Icotinib	CIViC C	EID10914
EGFR T790M AND VOPP1::EGFR Fusion	Lung Adenocarcinoma	Resistance	Icotinib	CIViC C	EID10895

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 1 clinical and 2 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

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

Molecule	Source	Status	Shared targets
AFATINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR
SELUMETINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR
ABEMACICLIB	ChEMBL	Phase 4 (approved)	EGFR
ACALABRUTINIB	ChEMBL	Phase 4 (approved)	EGFR
AFATINIB DIMALEATE	ChEMBL	Phase 4 (approved)	EGFR
ALECTINIB	ChEMBL	Phase 4 (approved)	EGFR
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	EGFR
AXITINIB	ChEMBL	Phase 4 (approved)	EGFR
BACITRACIN	ChEMBL	Phase 4 (approved)	EGFR
BITHIONOL	ChEMBL	Phase 4 (approved)	EGFR
BOSUTINIB	ChEMBL	Phase 4 (approved)	EGFR
BRIGATINIB	ChEMBL	Phase 4 (approved)	EGFR
CABOZANTINIB	ChEMBL	Phase 4 (approved)	EGFR
CERITINIB	ChEMBL	Phase 4 (approved)	EGFR
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	EGFR
CHROMIC CHLORIDE	ChEMBL	Phase 4 (approved)	EGFR
CISPLATIN	ChEMBL	Phase 4 (approved)	EGFR
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	EGFR
COLISTIN	ChEMBL	Phase 4 (approved)	EGFR
CRIZOTINIB	ChEMBL	Phase 4 (approved)	EGFR
DACOMITINIB	ChEMBL	Phase 4 (approved)	EGFR
DASATINIB	ChEMBL	Phase 4 (approved)	EGFR
DOBUTAMINE	ChEMBL	Phase 4 (approved)	EGFR
DOCETAXEL	ChEMBL	Phase 4 (approved)	EGFR
EBASTINE	ChEMBL	Phase 4 (approved)	EGFR
ECONAZOLE	ChEMBL	Phase 4 (approved)	EGFR
ERLOTINIB	ChEMBL	Phase 4 (approved)	EGFR
FEDRATINIB	ChEMBL	Phase 4 (approved)	EGFR
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	EGFR
GEFITINIB	ChEMBL	Phase 4 (approved)	EGFR
GENTIAN VIOLET	ChEMBL	Phase 4 (approved)	EGFR
GILTERITINIB	ChEMBL	Phase 4 (approved)	EGFR
HEXACHLOROPHENE	ChEMBL	Phase 4 (approved)	EGFR
IBRUTINIB	ChEMBL	Phase 4 (approved)	EGFR
IMATINIB	ChEMBL	Phase 4 (approved)	EGFR
LAPATINIB	ChEMBL	Phase 4 (approved)	EGFR
LAPATINIB DITOSYLATE	ChEMBL	Phase 4 (approved)	EGFR
LAZERTINIB	ChEMBL	Phase 4 (approved)	EGFR
LEVODOPA	ChEMBL	Phase 4 (approved)	EGFR
LORLATINIB	ChEMBL	Phase 4 (approved)	EGFR
METHYLDOPA	ChEMBL	Phase 4 (approved)	EGFR
MICONAZOLE	ChEMBL	Phase 4 (approved)	EGFR
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	EGFR
MITOXANTRONE	ChEMBL	Phase 4 (approved)	EGFR
MOBOCERTINIB	ChEMBL	Phase 4 (approved)	EGFR
MONTELUKAST	ChEMBL	Phase 4 (approved)	EGFR
NELFINAVIR	ChEMBL	Phase 4 (approved)	EGFR
NERATINIB	ChEMBL	Phase 4 (approved)	EGFR
NICLOSAMIDE	ChEMBL	Phase 4 (approved)	EGFR
OLMUTINIB	ChEMBL	Phase 4 (approved)	EGFR
OSIMERTINIB	ChEMBL	Phase 4 (approved)	EGFR
PERHEXILINE	ChEMBL	Phase 4 (approved)	EGFR
PONATINIB	ChEMBL	Phase 4 (approved)	EGFR
SORAFENIB	ChEMBL	Phase 4 (approved)	EGFR
SULOCTIDIL	ChEMBL	Phase 4 (approved)	EGFR
SUNITINIB	ChEMBL	Phase 4 (approved)	EGFR
TAMOXIFEN	ChEMBL	Phase 4 (approved)	EGFR
TERFENADINE	ChEMBL	Phase 4 (approved)	EGFR
THIORIDAZINE	ChEMBL	Phase 4 (approved)	EGFR
TRIBROMSALAN	ChEMBL	Phase 4 (approved)	EGFR