U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C22H21N3O4
Molecular Weight 391.4207
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ICOTINIB

SMILES

C#Cc1cccc(c1)Nc2c3cc4c(cc3ncn2)OCCOCCOCCO4

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
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.

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.728 mg/L
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

AUC

ValueDoseCo-administeredAnalytePopulation
3.22 mg × h/L
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
6.02 h
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1.5%
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

Doses

DosePopulationAdverse 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:
unhealthy, Median age 56 years
Health Status: unhealthy
Age Group: Median age 56 years
Sex: M+F
Sources:
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:
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:
unhealthy, Median age 57 years
Health Status: unhealthy
Age Group: Median age 57 years
Sex: M+F
Sources:
DLT: Rash...
Dose limiting toxicities:
Rash (grade 3, 16.7%)
Sources:
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:
unhealthy, Median age 57 years
Health Status: unhealthy
Age Group: Median age 57 years
Sex: M+F
Sources:
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:
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:
unhealthy, Median age 57 years
Health Status: unhealthy
Age Group: Median age 57 years
Sex: M+F
Sources:
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:
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:
unhealthy, Median age 57 years
Health Status: unhealthy
Age Group: Median age 57 years
Sex: M+F
Sources:
DLT: Rash, Hand and foot syndrome...
Dose limiting toxicities:
Rash (grade 3, 16.7%)
Hand and foot syndrome (grade 3, 16.7%)
Sources:
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:
unhealthy, Median age 58 years
Health Status: unhealthy
Age Group: Median age 58 years
Sex: M+F
Sources:
Other AEs: Mouth ulceration...
Other AEs:
Mouth ulceration (grade 3, 16.7%)
Sources:
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:
unhealthy, Median age 58 years
Health Status: unhealthy
Age Group: Median age 58 years
Sex: M+F
Sources:
Other AEs: Transaminases increased...
Other AEs:
Transaminases increased (grade 3, 7.7%)
Sources:
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:
healthy
Health Status: healthy
Sex: M
Sources:
AEs

AEs

AESignificanceDosePopulation
Leukopenia grade 3-4, 0.7%
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:
unhealthy, Median age 56 years
Health Status: unhealthy
Age Group: Median age 56 years
Sex: M+F
Sources:
ALT increased grade 3-4, 2%
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:
unhealthy, Median age 56 years
Health Status: unhealthy
Age Group: Median age 56 years
Sex: M+F
Sources:
Aspartate aminotransferase increased grade 3-4, 2.7%
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:
unhealthy, Median age 56 years
Health Status: unhealthy
Age Group: Median age 56 years
Sex: M+F
Sources:
Rash grade 3, 16.7%
DLT
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:
unhealthy, Median age 57 years
Health Status: unhealthy
Age Group: Median age 57 years
Sex: M+F
Sources:
Transaminases increased grade 3-4, 1%
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:
unhealthy, Median age 57 years
Health Status: unhealthy
Age Group: Median age 57 years
Sex: M+F
Sources:
Pain grade 3-4, 2%
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:
unhealthy, Median age 57 years
Health Status: unhealthy
Age Group: Median age 57 years
Sex: M+F
Sources:
Nausea grade 3-4, <1%
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:
unhealthy, Median age 57 years
Health Status: unhealthy
Age Group: Median age 57 years
Sex: M+F
Sources:
Rash grade 3-4, <1%
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:
unhealthy, Median age 57 years
Health Status: unhealthy
Age Group: Median age 57 years
Sex: M+F
Sources:
ALT increased grade 3-4, 1%
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:
unhealthy, Median age 57 years
Health Status: unhealthy
Age Group: Median age 57 years
Sex: M+F
Sources:
Aspartate aminotransferase increased grade 3-4, 1%
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:
unhealthy, Median age 57 years
Health Status: unhealthy
Age Group: Median age 57 years
Sex: M+F
Sources:
Dizziness grade 3-4, 1%
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:
unhealthy, Median age 57 years
Health Status: unhealthy
Age Group: Median age 57 years
Sex: M+F
Sources:
Impaired liver function grade 3-4, 1%
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:
unhealthy, Median age 57 years
Health Status: unhealthy
Age Group: Median age 57 years
Sex: M+F
Sources:
Leucopenia grade 3-4, 1%
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:
unhealthy, Median age 57 years
Health Status: unhealthy
Age Group: Median age 57 years
Sex: M+F
Sources:
Neutropenia grade 3-4, 1%
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:
unhealthy, Median age 57 years
Health Status: unhealthy
Age Group: Median age 57 years
Sex: M+F
Sources:
Numbness of limbs grade 3-4, 2%
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:
unhealthy, Median age 57 years
Health Status: unhealthy
Age Group: Median age 57 years
Sex: M+F
Sources:
Hand and foot syndrome grade 3, 16.7%
DLT
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:
unhealthy, Median age 57 years
Health Status: unhealthy
Age Group: Median age 57 years
Sex: M+F
Sources:
Rash grade 3, 16.7%
DLT
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:
unhealthy, Median age 57 years
Health Status: unhealthy
Age Group: Median age 57 years
Sex: M+F
Sources:
Mouth ulceration grade 3, 16.7%
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:
unhealthy, Median age 58 years
Health Status: unhealthy
Age Group: Median age 58 years
Sex: M+F
Sources:
Transaminases increased grade 3, 7.7%
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:
unhealthy, Median age 58 years
Health Status: unhealthy
Age Group: Median age 58 years
Sex: M+F
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Drug as perpetrator​Drug as victim
PubMed

PubMed

TitleDatePubMed
Phase I study of icotinib hydrochloride (BPI-2009H), an oral EGFR tyrosine kinase inhibitor, in patients with advanced NSCLC and other solid tumors.
2011 Aug
Synthesis and biological evaluation of crown ether fused quinazoline analogues as potent EGFR inhibitors.
2012 Oct 1
Patents

Sample Use Guides

125 mg q8h/day
Route of Administration: Oral
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.
Name Type Language
ICOTINIB
WHO-DD  
Common Name English
BPI-2009
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
Created by admin on Sat Jun 26 04:46:46 UTC 2021 , Edited by admin on Sat Jun 26 04:46:46 UTC 2021
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 04:46:46 UTC 2021 , Edited by admin on Sat Jun 26 04:46:46 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C138996
Created by admin on Sat Jun 26 04:46:46 UTC 2021 , Edited by admin on Sat Jun 26 04:46:46 UTC 2021
PRIMARY
FDA UNII
9G6U5L461Q
Created by admin on Sat Jun 26 04:46:46 UTC 2021 , Edited by admin on Sat Jun 26 04:46:46 UTC 2021
PRIMARY
PUBCHEM
22024915
Created by admin on Sat Jun 26 04:46:46 UTC 2021 , Edited by admin on Sat Jun 26 04:46:46 UTC 2021
PRIMARY
EVMPD
SUB179563
Created by admin on Sat Jun 26 04:46:46 UTC 2021 , Edited by admin on Sat Jun 26 04:46:46 UTC 2021
PRIMARY
MESH
C531470
Created by admin on Sat Jun 26 04:46:46 UTC 2021 , Edited by admin on Sat Jun 26 04:46:46 UTC 2021
PRIMARY
IUPHAR
7641
Created by admin on Sat Jun 26 04:46:46 UTC 2021 , Edited by admin on Sat Jun 26 04:46:46 UTC 2021
PRIMARY
WIKIPEDIA
Icotinib
Created by admin on Sat Jun 26 04:46:46 UTC 2021 , Edited by admin on Sat Jun 26 04:46:46 UTC 2021
PRIMARY
CAS
610798-31-7
Created by admin on Sat Jun 26 04:46:46 UTC 2021 , Edited by admin on Sat Jun 26 04:46:46 UTC 2021
PRIMARY
DRUG BANK
DB11737
Created by admin on Sat Jun 26 04:46:46 UTC 2021 , Edited by admin on Sat Jun 26 04:46:46 UTC 2021
PRIMARY
DRUG CENTRAL
5209
Created by admin on Sat Jun 26 04:46:46 UTC 2021 , Edited by admin on Sat Jun 26 04:46:46 UTC 2021
PRIMARY
EPA CompTox
610798-31-7
Created by admin on Sat Jun 26 04:46:46 UTC 2021 , Edited by admin on Sat Jun 26 04:46:46 UTC 2021
PRIMARY