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Details

Stereochemistry ACHIRAL
Molecular Formula C22H24ClFN4O3
Molecular Weight 446.902
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GEFITINIB

SMILES

COC1=C(OCCCN2CCOCC2)C=C3C(NC4=CC(Cl)=C(F)C=C4)=NC=NC3=C1

InChI

InChIKey=XGALLCVXEZPNRQ-UHFFFAOYSA-N
InChI=1S/C22H24ClFN4O3/c1-29-20-13-19-16(12-21(20)31-8-2-5-28-6-9-30-10-7-28)22(26-14-25-19)27-15-3-4-18(24)17(23)11-15/h3-4,11-14H,2,5-10H2,1H3,(H,25,26,27)

HIDE SMILES / InChI

Molecular Formula C22H24ClFN4O3
Molecular Weight 446.902
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Gefitinib is an anilinoquinazoline with antineoplastic activity. Gefitinib inhibits the epidermal growth factor receptor (EGFR) tyrosine kinase by binding to the adenosine triphosphate (ATP)-binding site of the enzyme. Thus the function of the EGFR tyrosine kinase in activating the Ras signal transduction cascade is inhibited; and malignant cells are inhibited. Gefitinib is the first selective inhibitor of the EGFR tyrosine kinase which is also referred to as Her1 or ErbB-1. EGFR is overexpressed in the cells of certain types of human carcinomas - for example in lung and breast cancers. Overexpression leads to inappropriate activation of the apoptotic Ras signal transduction cascade, eventually leading to uncontrolled cell proliferation. Gefitinib is used for the continued treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of either platinum-based or docetaxel chemotherapies.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
1.0 nM [IC50]
19.27 µM [IC50]
1.23 µM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Iressa

Cmax

ValueDoseCo-administeredAnalytePopulation
57.5 ng/mL
250 mg single, oral
GEFITINIB plasma
Homo sapiens
724 ng/mL
250 mg 1 times / day steady-state, oral
GEFITINIB plasma
Homo sapiens
213 ng/mL
500 mg single, oral
GEFITINIB plasma
Homo sapiens
2160 ng/mL
700 mg 1 times / day multiple, oral
GEFITINIB plasma
Homo sapiens
579 ng/mL
400 mg 1 times / day multiple, oral
GEFITINIB plasma
Homo sapiens
178 ng/mL
100 mg 1 times / day multiple, oral
GEFITINIB plasma
Homo sapiens
57.45 ng/mL
250 mg single, oral
GEFITINIB plasma
Homo sapiens
2210 ng/mL
400 mg/m² 1 times / day multiple, oral
GEFITINIB plasma
Homo sapiens
466 ng/mL
250 mg 1 times / day steady-state, oral
GEFITINIB plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
1415 ng × h/mL
250 mg single, oral
GEFITINIB plasma
Homo sapiens
13103 ng × h/mL
250 mg 1 times / day steady-state, oral
GEFITINIB plasma
Homo sapiens
6181 ng × h/mL
500 mg single, oral
GEFITINIB plasma
Homo sapiens
42314 ng × h/mL
700 mg 1 times / day multiple, oral
GEFITINIB plasma
Homo sapiens
10026 ng × h/mL
400 mg 1 times / day multiple, oral
GEFITINIB plasma
Homo sapiens
2985 ng × h/mL
100 mg 1 times / day multiple, oral
GEFITINIB plasma
Homo sapiens
1415 ng × h/mL
250 mg single, oral
GEFITINIB plasma
Homo sapiens
29.3 μg × h/mL
400 mg/m² 1 times / day multiple, oral
GEFITINIB plasma
Homo sapiens
8896 ng × h/mL
250 mg 1 times / day steady-state, oral
GEFITINIB plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
21.2 h
250 mg single, oral
GEFITINIB plasma
Homo sapiens
25 h
250 mg 1 times / day steady-state, oral
GEFITINIB plasma
Homo sapiens
28.2 h
500 mg single, oral
GEFITINIB plasma
Homo sapiens
72.9 h
700 mg 1 times / day multiple, oral
GEFITINIB plasma
Homo sapiens
38.1 h
400 mg 1 times / day multiple, oral
GEFITINIB plasma
Homo sapiens
55.2 h
100 mg 1 times / day multiple, oral
GEFITINIB plasma
Homo sapiens
23.83 h
250 mg single, oral
GEFITINIB plasma
Homo sapiens
11.9 h
400 mg/m² 1 times / day multiple, oral
GEFITINIB plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
9%
250 mg single, oral
GEFITINIB plasma
Homo sapiens
10%
GEFITINIB plasma
Homo sapiens

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Sample Use Guides

In Vivo Use Guide
250 mg orally once a day
Route of Administration: Oral
In Vitro Use Guide
Gefitinib could inhibit highly expressed EGFR cell growth in a dose-dependent manner in the range of dose from 0.10 to 102.4 uM
Substance Class Chemical
Record UNII
S65743JHBS
Record Status Validated (UNII)
Record Version