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Details

Stereochemistry ACHIRAL
Molecular Formula C22H21N3O4.ClH
Molecular Weight 427.881
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ICOTINIB HYDROCHLORIDE

SMILES

Cl.C#CC1=CC(NC2=NC=NC3=C2C=C4OCCOCCOCCOC4=C3)=CC=C1

InChI

InChIKey=PNNGXMJMUUJHAV-UHFFFAOYSA-N
InChI=1S/C22H21N3O4.ClH/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);1H

HIDE SMILES / InChI

Description

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 TargetPharmacologyConditionPotency
5.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Conmana
Primary
Unknown
Primary
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
0.728 mg/L
100 mg single, oral
ICOTINIB plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
3.22 mg × h/L
100 mg single, oral
ICOTINIB plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
6.02 h
100 mg single, oral
ICOTINIB plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
1.5%
100 mg single, oral
ICOTINIB plasma
Homo sapiens

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

PubMed

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.