ICOTINIB

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H21N3O4
Molecular Weight	391.4198
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C#CC1=CC=CC(NC2=NC=NC3=CC4=C(OCCOCCOCCO4)C=C23)=C1

InChI

InChIKey=QQLKULDARVNMAL-UHFFFAOYSA-N

InChI=1S/C22H21N3O4/c1-2-16-4-3-5-17(12-16)25-22-18-13-20-21(14-19(18)23-15-24-22)29-11-9-27-7-6-26-8-10-28-20/h1,3-5,12-15H,6-11H2,(H,23,24,25)

HIDE SMILES / InChI

Molecular Formula	C22H21N3O4
Molecular Weight	391.4198
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=717145 | http://www.lillyasiaventures.com/en/home.asp?lm_id=13&lm_id_2=15&id=9 | https://www.ncbi.nlm.nih.gov/pubmed/26831237 | https://www.ncbi.nlm.nih.gov/pubmed/28054523 | https://www.ncbi.nlm.nih.gov/pubmed/26980473 | http://betapharma.com/wp-content/uploads/2016/04/APLCC-Poster-final.pdf

Icotinib is an orally available quinazoline-based inhibitor of epidermal growth factor receptor. It selectively inhibits the wild-type and several mutated forms of EGFR tyrosine kinase. The major organ of icotinib metabolism is the liver, with the primarily enzymes being CYP2C19 and CYP3A4 from the cytochrome P450 monooxygenase system. Icotinib Hydrochloride was approved for the treatment of patients with advanced stage Nonsmall cell lung cancer by the State Food and Drug Administration (SFDA) of China. The major drug related adverse reactions of the traditional cytotoxic agents include rash, diarrhea, severe bone marrow suppression, neuropathy, hair loss, and gastrointestinal reactions. Icotinib is under investigation as an active agent against other EGFR mutation-positive cancers, like lung adenocarcinoma, oesophageal cancer, nasopharyngeal cancer and others.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Epidermal growth factor receptor erbB1 62 Target ID: CHEMBL203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22112293	Inhibitor 8504	5.0 nM [IC50]
Cytochrome P450 2C19 51 Target ID: CHEMBL3622 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26831237	Substrate 661
Cytochrome P450 3A4 127 Target ID: CHEMBL340 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26831237	Substrate 661

Conditions

Condition	Modality	Highest Phase	Product
Non-small cell lung cancer 211 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24836053	Primary	Approved 8583	Conmana Approved Use Icotinib hydrochloride is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) indicated for non-small cell lung cancer. Launch Date 2011
Lung adenocarcinoma 8 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27822065 https://www.ncbi.nlm.nih.gov/pubmed/28054523	Primary	Phase IV 63	Unknown Approved Use Unknown
Esophageal cancer 12 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27013591 https://www.ncbi.nlm.nih.gov/pubmed/26980473	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
2.06 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24488324/	350 mg single, oral dose: 350 mg route of administration: Oral experiment type: SINGLE co-administered:		ICOTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
0.728 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24488324/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		ICOTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
12.3 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24488324/	350 mg single, oral dose: 350 mg route of administration: Oral experiment type: SINGLE co-administered:		ICOTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.22 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24488324/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		ICOTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
6.47 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24488324/	350 mg single, oral dose: 350 mg route of administration: Oral experiment type: SINGLE co-administered:		ICOTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.02 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24488324/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		ICOTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
1.5% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24488324/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		ICOTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
125 mg 3 times / day multiple, oral Recommended Dose: 125 mg, 3 times / day Route: oral Route: multiple Dose: 125 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28945850/	unhealthy, Median age 56 years Health Status: unhealthy Age Group: Median age 56 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/28945850/	Other AEs: Leukopenia, ALT increased... Other AEs: Leukopenia (grade 3-4, 0.7%) ALT increased (grade 3-4, 2%) Aspartate aminotransferase increased (grade 3-4, 2.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/28945850/
500 mg 3 times / day multiple, oral MTD Dose: 500 mg, 3 times / day Route: oral Route: multiple Dose: 500 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27789778/	unhealthy, Median age 57 years Health Status: unhealthy Age Group: Median age 57 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/27789778/	DLT: Rash... Dose limiting toxicities: Rash (grade 3, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/27789778/
125 mg 3 times / day multiple, oral Recommended Dose: 125 mg, 3 times / day Route: oral Route: multiple Dose: 125 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23948351/	unhealthy, Median age 57 years Health Status: unhealthy Age Group: Median age 57 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/23948351/	Other AEs: Rash, Pain... Other AEs: Rash (grade 3-4, <1%) Pain (grade 3-4, 2%) Transaminases increased (grade 3-4, 1%) Nausea (grade 3-4, <1%) Sources: https://pubmed.ncbi.nlm.nih.gov/23948351/
125 mg 3 times / day multiple, oral Recommended Dose: 125 mg, 3 times / day Route: oral Route: multiple Dose: 125 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28734822/	unhealthy, Median age 57 years Health Status: unhealthy Age Group: Median age 57 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/28734822/	Other AEs: ALT increased, Aspartate aminotransferase increased... Other AEs: ALT increased (grade 3-4, 1%) Aspartate aminotransferase increased (grade 3-4, 1%) Impaired liver function (grade 3-4, 1%) Leucopenia (grade 3-4, 1%) Neutropenia (grade 3-4, 1%) Dizziness (grade 3-4, 1%) Numbness of limbs (grade 3-4, 2%) Sources: https://pubmed.ncbi.nlm.nih.gov/28734822/
625 mg 3 times / day multiple, oral Studied dose Dose: 625 mg, 3 times / day Route: oral Route: multiple Dose: 625 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27789778/	unhealthy, Median age 57 years Health Status: unhealthy Age Group: Median age 57 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/27789778/	DLT: Rash, Hand and foot syndrome... Dose limiting toxicities: Rash (grade 3, 16.7%) Hand and foot syndrome (grade 3, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/27789778/
125 mg 3 times / day multiple, oral Recommended Dose: 125 mg, 3 times / day Route: oral Route: multiple Dose: 125 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21144613/	unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/21144613/	Other AEs: Mouth ulceration... Other AEs: Mouth ulceration (grade 3, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/21144613/
100 mg 3 times / day multiple, oral Studied dose Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21144613/	unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/21144613/	Other AEs: Transaminases increased... Other AEs: Transaminases increased (grade 3, 7.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/21144613/
1075 mg 1 times / day single, oral Highest studied dose Dose: 1075 mg, 1 times / day Route: oral Route: single Dose: 1075 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24488324/	healthy Health Status: healthy Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/24488324/	Sources: https://pubmed.ncbi.nlm.nih.gov/24488324/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193	substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
UGT1A1 246 CYP1A2 2153 BCRP 910	CYP1A2 1197 CYP2B6 776 CYP2C8 810 CYP2C19 1119 CYP3A5 446

Drug as perpetrator

Target	Modality	Activity
UGT1A1 303	inhibitor 4027 Sources: https://www.sciencedirect.com/science/article/pii/S2211383517301363 Page: -	yes [IC50 8.76 uM]
BCRP 985	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147343/ Page: -	yes
CYP1A2 2333	inhibitor 4027 Sources: https://www.dovepress.com/comparative-review-of-drug-drug-interactions-with-epidermal-growth-fac-peer-reviewed-fulltext-article-OTT Page: -	yes

Drug as victim

Target	Modality	Activity
CYP3A4 1946	substrate 4014 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0022354917308778?via%3Dihub Page: -	major
CYP2B6 776	substrate 4014 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0022354917308778?via%3Dihub Page: -	no
CYP2C19 1119	substrate 4014 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0022354917308778?via%3Dihub Page: -	no
CYP2C8 810	substrate 4014 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0022354917308778?via%3Dihub Page: -	no
CYP2C9 1193	substrate 4014 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0022354917308778?via%3Dihub Page: -	no
CYP2D6 1388	substrate 4014 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0022354917308778?via%3Dihub Page: -	no
CYP1A2 1197	substrate 4014 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0022354917308778?via%3Dihub Page: -	yes
CYP3A5 446	substrate 4014 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0022354917308778?via%3Dihub Page: -	yes

PubMed

Title	Date	PubMed
Synthesis and biological evaluation of crown ether fused quinazoline analogues as potent EGFR inhibitors.	2012-10-01	22959248
Icotinib (BPI-2009H), a novel EGFR tyrosine kinase inhibitor, displays potent efficacy in preclinical studies.	2012-05	22112293
Phase I study of icotinib hydrochloride (BPI-2009H), an oral EGFR tyrosine kinase inhibitor, in patients with advanced NSCLC and other solid tumors.	2011-08	21144613

Patents

Sample Use Guides

In Vivo Use Guide

125 mg q8h/day

Route of Administration: Oral

In Vitro Use Guide

Icotinib induces G1 phase cell cycle arrest and apoptosis in HCC827 cells. There was an increase in the number of cells in G1 phase after exposure to 0.01 and 0.1 uM icotinib for 24 h. The percentage of cells in G1 phase increased from 45.41 to 68.41 and 78.30, respectively. Furthermore, the percentages of apoptotic cells were elevated from 4.26% to 6.31% and 18.85%, after treatment with 0.01 and 0.1 uM icotinib.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 21:14:42 GMT 2025` Edited by `admin` on `Mon Mar 31 21:14:42 GMT 2025`
Record UNII	9G6U5L461Q
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BPI-2009

Preferred Name

English

ICOTINIB

Common Name

English

Icotinib [WHO-DD]

Common Name

English

(1,4,7,10)TETRAOXACYCLODODECINO(2,3-G)QUINAZOLIN-4-AMINE, N-(3-ETHYNYLPHENYL)-7,8,10,11,13,14-HEXAHYDRO-

Systematic Name

English

Classification Tree Code System Code

WHO-ATC

L01XE48