ERLOTINIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H23N3O4
Molecular Weight	393.4357
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COCCOC1=CC2=NC=NC(NC3=CC=CC(=C3)C#C)=C2C=C1OCCOC

InChI

InChIKey=AAKJLRGGTJKAMG-UHFFFAOYSA-N

InChI=1S/C22H23N3O4/c1-4-16-6-5-7-17(12-16)25-22-18-13-20(28-10-8-26-2)21(29-11-9-27-3)14-19(18)23-15-24-22/h1,5-7,12-15H,8-11H2,2-3H3,(H,23,24,25)

HIDE SMILES / InChI

Molecular Formula	C22H23N3O4
Molecular Weight	393.4357
Charge	0
Count

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

Description
Sources: http://www.drugbank.ca/drugs/DB00530
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021743s14s16lbl.pdf

Erlotinib hydrochloride (trade name Tarceva, Genentech/OSIP, originally coded as OSI-774) is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer. Similar to gefitinib, erlotinib specifically targets the epidermal growth factor receptor (EGFR) tyrosine kinase. It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor. Erlotinib has recently been shown to be a potent inhibitor of JAK2V617F activity. JAK2V617F is a mutant of tyrosine kinase JAK2, is found in most patients with polycythemia vera (PV) and a substantial proportion of patients with idiopathic myelofibrosis or essential thrombocythemia. The study suggests that erlotinib may be used for treatment of JAK2V617F-positive PV and other myeloproliferative disorders. The mechanism of clinical antitumor action of erlotinib is not fully characterized. Erlotinib inhibits the intracellular phosphorylation of tyrosine kinase associated with the epidermal growth factor receptor (EGFR). Specificity of inhibition with regard to other tyrosine kinase receptors has not been fully characterized. EGFR is expressed on the cell surface of normal cells and cancer cells.

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/25882519	Antagonist 2849	1.2 nM [IC50]
Pregnane X receptor 36 Target ID: CHEMBL3401 Sources: http://www.drugbank.ca/drugs/DB00530	Agonist 2752
ATP-binding cassette sub-family G member 2 16 Target ID: CHEMBL5393 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27418107	Inhibitor 8504	2.23 µM [IC50]
PANC-1 5 Target ID: CHEMBL614139 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27010345	Inhibitor 8504	0.02 µM [IC50]
Serine/threonine-protein kinase B-raf 21 Target ID: CHEMBL5145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27010345	Inhibitor 8504	0.08 µM [IC50]
Epidermal growth factor receptor 49 Target ID: CHEMBL2363049 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27010345	Antagonist 2849	0.05 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Locally advanced or metastatic non-small cell lung cancer 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021743s14s16lbl.pdf	Primary		Approved 8583	TARCEVA Approved Use TARCEVA is a kinase inhibitor indicated for: Maintenance treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. Treatment of locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. First-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer, in combination with gemcitabine. Launch Date 2004
Locally advanced, unresectable or metastatic pancreatic cancer 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021743s14s16lbl.pdf	Primary		Approved 8583	TARCEVA Approved Use TARCEVA is a kinase inhibitor indicated for: Maintenance treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. Treatment of locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. First-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer, in combination with gemcitabine. Launch Date 2004

C_max

Value	Dose	Analyte	Population
1969.5 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01032070	85 mg/m^2 1 times / day steady, oral dose: 85 mg/m^2 route of administration: oral experiment type: steady co-administered:	ERLOTINIB plasma	Homo sapiens population: unhealthy age: Children sex: UNKNOWN food status: UNKNOWN
4.07 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19956953	100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ERLOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.25 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19956953	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ERLOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1108.89 ng/mL EXPERIMENT http://doi.org/10.4172/jbb.1000190	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	ERLOTINIB HYDROCHLORIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.09 μg/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF	150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ERLOTINIB HYDROCHLORIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED

AUC

Value	Dose	Analyte	Population
26716.7 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01032070	85 mg/m^2 1 times / day steady, oral dose: 85 mg/m^2 route of administration: oral experiment type: steady co-administered:	ERLOTINIB plasma	Homo sapiens population: unhealthy age: Children sex: UNKNOWN food status: UNKNOWN
32 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19956953	100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ERLOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
29.9 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19956953	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ERLOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
25489.41 ng × h/mL EXPERIMENT http://doi.org/10.4172/jbb.1000190	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	ERLOTINIB HYDROCHLORIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
15.2 μg × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF	150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ERLOTINIB HYDROCHLORIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Analyte	Population
12.4 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19956953	100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ERLOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14.4 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19956953	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ERLOTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
36.2 h OTHER https://www.medicine.com/drug/erlotinib/hcp	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	ERLOTINIB HYDROCHLORIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
14.33 h EXPERIMENT http://doi.org/10.4172/jbb.1000190	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	ERLOTINIB HYDROCHLORIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14.75 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF	150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	ERLOTINIB HYDROCHLORIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
7% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021743s14s16lbl.pdf			ERLOTINIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
7% OTHER https://www.medicine.com/drug/erlotinib/hcp	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		ERLOTINIB HYDROCHLORIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252	inhibitor 2438 substrate 1193	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 1057 UGT1A1 246 UGT1A9 148 CYP1A1 132 CYP1A2 2153	CYP1A2 1197 CYP2C8 810 CYP1A1 389 CYP1B1 104 CYP2C19 1119 CYP3A4/5 91

Drug as perpetrator

Target	Modality	Activity
UGT1A1 303	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=51 Page: -	yes [IC50 0.93 uM]
UGT1A9 155	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=51 Page: -	yes [IC50 31 uM]
CYP1A1 272	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=48 Page: -	yes [IC50 <0.1 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=10 Page: -	yes [Ki 10 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=10 Page: -	yes [Ki 14.7 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=49 Page: -	yes [Ki 20 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=49 Page: -	yes [Ki 35.7 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=10 Page: -	yes [Ki 44 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=10 Page: -	major [Km 5.9 uM]	yes (co-administration study) Comment: Coadministration of erlotinib with ketoconazole, a potent inhibitor of CYP3A4, resulted in a significant (67%) increase in erlotinib exposure (Study NP16612). The CYP3A4 inducer rifampicin has been demonstrated to impact the exposure to erlotinib; in Study NP16638 co-administration led to a 64% reduction in erlotinib AUC. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=10 Page: -
CYP2C8 810	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=10 Page: -	minor
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=39 Page: -	no
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=39 Page: -	no
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=39 Page: -	no
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=47 Page: -	yes [Km 24 uM]
CYP1A1 389	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=10 Page: -	yes
CYP1B1 104	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=10 Page: -	yes
CYP3A4/5 91	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=47 Page: -	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=11 Page: -

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:114785	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:114785
ChemicalBook	CB9285914	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9285914
eMolecules	901844	https://www.emolecules.com/cgi-bin/more?vid=901844
MolPort	MolPort-003-847-084	https://www.molport.com/shop/molecule-link/MolPort-003-847-084
ZINC	ZINC000001546066	http://zinc15.docking.org/substances/ZINC000001546066

PubMed

Title	Date	PubMed
Benzamides and benzamidines as specific inhibitors of epidermal growth factor receptor and v-Src protein tyrosine kinases.	2004-07-01	15186837
The role of erlotinib (Tarceva, OSI 774) in the treatment of non-small cell lung cancer.	2004-06-15	15217965
Epidermal growth factor receptor tyrosine kinase inhibitors.	2004-06-14	15150574
Targeting non-small cell lung cancer with epidermal growth factor tyrosine kinase inhibitors: where do we stand, where do we go.	2004-06	15182824
EGFR inhibitors square off at ASCO.	2004-06	15175668
Antitumor activity of erlotinib (OSI-774, Tarceva) alone or in combination in human non-small cell lung cancer tumor xenograft models.	2004-06	15166626
Combination treatment of glioblastoma multiforme cell lines with the anti-malarial artesunate and the epidermal growth factor receptor tyrosine kinase inhibitor OSI-774.	2004-05-01	15081868
Current data and ongoing trials in patients with recurrent non-small-cell lung cancer.	2004-05	15217532
[Lung cancer: molecular targeting therapy].	2004-05	15168452
New cytotoxic and molecular-targeted therapies of head and neck tumors.	2004-05	15069317
Identification of epidermal growth factor receptor-derived peptides immunogenic for HLA-A2(+) cancer patients.	2004-04-19	15083186
Gateways to clinical trials.	2004-04	15148527
Epidermal growth factor receptor inhibitors for the treatment of colorectal cancer: a promise fulfilled?	2004-04	15134356
Epidermal growth factor receptor tyrosine kinase inhibitors: evolving role in the treatment of solid tumors.	2004-04	15108418
Rationale and clinical validation of epidermal growth factor receptor as a target in the treatment of head and neck cancer.	2004-04	15057134
Emerging role of epidermal growth factor receptor inhibition in therapy for advanced malignancy: focus on NSCLC.	2004-03-01	14967461
The HER receptor family: a rich target for therapeutic development.	2004-03-01	14967453
The role of EGFR inhibitors in nonsmall cell lung cancer.	2004-03	15075904
[Bronchioloalveolar carcinoma (BAC)].	2004-03	15045932
Inverse correlation of epidermal growth factor receptor messenger RNA induction and suppression of anchorage-independent growth by OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in glioblastoma multiforme cell lines.	2004-03	15035290
Gateways to clinical trials.	2004-02-28	14988742
Emerging treatments in oncology: focus on tyrosine kinase (erbB) receptor inhibitors.	2004-02-18	14965154
Gefitinib ('Iressa', ZD1839) and new epidermal growth factor receptor inhibitors.	2004-02-09	14760365
Novel treatments in non-small cell lung cancer.	2004-02	15005292
Pharmacology of oral chemotherapy agents.	2004-01-07	14705495
Synthesis and SAR of potent EGFR/erbB2 dual inhibitors.	2004-01-05	14684309
Multicenter phase II study of erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent or metastatic squamous cell cancer of the head and neck.	2004-01-01	14701768
Lung cancer: looking ahead in 2004.	2004-01	14967070
Review of epidermal growth factor receptor biology.	2004	15142631
Potential role for epidermal growth factor receptor inhibitors in combined-modality therapy for non-small-cell lung cancer.	2004	15142630
Emerging roles of targeted small molecule protein-tyrosine kinase inhibitors in cancer therapy.	2004	14977353
HER1/EGFR targeting: refining the strategy.	2004	14755015
Distribution and function of EGFR in human tissue and the effect of EGFR tyrosine kinase inhibition.	2003-12-12	14666659
For investigational targeted drugs, combination trials pose challenges.	2003-12-03	14652234
Targeting the epidermal growth factor receptor in non-small cell lung cancer.	2003-12-01	14676101
Epidermal growth factor receptor tyrosine kinase inhibitors: application in non-small cell lung cancer.	2003-12	15025409
Tolerability of gefitinib in patients receiving treatment in everyday clinical practice.	2003-12	14661047
[Therapeutic implications of epidermal growth factor receptor in lung cancer].	2003-11	14763145
[Inhibitors of epidermal growth factor receptor and colorectal cancer].	2003-11	14763144
[Targeting of epidermal growth factor receptor and applications in ORL cancer].	2003-11	14763143
Identifying predictive and surrogate markers of erlotinib antitumor activity other than rash.	2003-11	14682121
Can rash associated with HER1/EGFR inhibition be used as a marker of treatment outcome?	2003-11	14682120
Clinical experience with the HER1/EGFR tyrosine kinase inhibitor erlotinib.	2003-11	14682119
Erlotinib: preclinical investigations.	2003-11	14682118
Targeting the HER1/EGFR receptor to improve outcomes in non-small-cell lung cancer.	2003-11	14682117
Epidermal growth factor receptor tyrosine kinase inhibitors in late stage clinical trials.	2003-11	14662002
Defining the role of the epidermal growth factor receptor in pancreatic cancer grown in vitro.	2003-11	14599602
Gateways to clinical trials.	2003-10	14671684
3D-QSAR and docking studies on 4-anilinoquinazoline and 4-anilinoquinoline epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors.	2003-08	14703120
Small-molecule epidermal growth factor receptor tyrosine kinase inhibitors.	2003	14657536

Patents

Sample Use Guides

In Vivo Use Guide

The dose for NSCLC is 150 mg/day. The dose for pancreatic cancer is 100 mg/day. All doses of TARCEVA should be taken on an empty stomach at least one hour before or two hours after food

Route of Administration: Oral

In Vitro Use Guide

Erlotinib (20 µM) inhibited 33.8% of the growth of T. gondii

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:27:50 GMT 2025` Edited by `admin` on `Mon Mar 31 18:27:50 GMT 2025`
Record UNII	J4T82NDH7E
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ERLOTINIB

Official Name

English

CP-358,774

Preferred Name

English

N-(3-ETHYNYLPHENYL)-6,7-BIS(2-METHOXYETHOXY)QUINAZOLIN-4-AMINE

Systematic Name

English

CP-358774

Code

English

RG-1415

Code

English

ERLOTINIB [EMA EPAR]

Common Name

English

R-1415

Code

English

Erlotinib [WHO-DD]

Common Name

English

CP-35877401

Code

English

ERLOTINIB [MI]

Common Name

English

erlotinib [INN]

Common Name

English

ERLOTINIB [VANDF]

Common Name

English

4-QUINAZOLINAMINE, N-(3-ETHYNYLPHENYL)-6,7-BIS(2-METHOXYETHOXY)-

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2167