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=C(C=C1OCCOC)C(NC3=CC(=CC=C3)C#C)=NC=N2

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

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 58 Target ID: CHEMBL203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25882519	Antagonist 2778	1.2 nM [IC50]
Pregnane X receptor 35 Target ID: CHEMBL3401 Sources: http://www.drugbank.ca/drugs/DB00530	Agonist 2678
ATP-binding cassette sub-family G member 2 16 Target ID: CHEMBL5393 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27418107	Inhibitor 8297	2.23 µM [IC50]
PANC-1 5 Target ID: CHEMBL614139 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27010345	Inhibitor 8297	0.02 µM [IC50]
Serine/threonine-protein kinase B-raf 20 Target ID: CHEMBL5145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27010345	Inhibitor 8297	0.08 µM [IC50]
Epidermal growth factor receptor 46 Target ID: CHEMBL2363049 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27010345	Antagonist 2778	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 8429	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 8429	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
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
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
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: food status:

AUC

Value	Dose	Analyte	Population
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
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
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: food status:

T_1/2

Value	Dose	Co-administered	Analyte	Population
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
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

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

Doses

Dose	Population	Adverse events
100 mg 1 times / day single, intravenous Highest studied dose Dose: 100 mg, 1 times / day Route: intravenous Route: single Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19956953/	unhealthy, Median age 54 years n = 6 Health Status: unhealthy Condition: solid tumors Age Group: Median age 54 years Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/19956953/	Sources: https://pubmed.ncbi.nlm.nih.gov/19956953/
150 mg 1 times / day multiple, oral Recommended\|MTD Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11432895/ https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/021743lbl.pdf	unhealthy, Median age 57 years n = 7 Health Status: unhealthy Condition: solid tumors Age Group: Median age 57 years Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/11432895/ https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/021743lbl.pdf	Other AEs: Mucositis, Diarrhea... Other AEs: Mucositis (grade 1-2, 28.6%) Diarrhea (grade 1-2, 85.7%) Hyperbilirubinemia (grade 1-2, 14.3%) Skin toxicity (grade 1-2, 28.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/11432895/ https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/021743lbl.pdf
200 mg 1 times / day multiple, oral Studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11432895/	unhealthy, Median age 57 years n = 6 Health Status: unhealthy Condition: solid tumors Age Group: Median age 57 years Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/11432895/	Other AEs: Diarrhea, Hyperbilirubinemia... Other AEs: Diarrhea (grade 1-2, 66.7%) Hyperbilirubinemia (grade 1-2, 33.3%) Skin toxicity (grade 1-2, 83.3%) Headache (grade 1-2, 33.3%) Diarrhea (grade 4, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/11432895/
100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Co-administed with:: Amrubicin(30 mg/m2; Days 1-3) Sources: https://pubmed.ncbi.nlm.nih.gov/26214085/	unhealthy, Median age 62 years n = 3 Health Status: unhealthy Condition: nonsmall cell lung cance Age Group: Median age 62 years Sex: M+F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/26214085/	Other AEs: Neutropenia... Other AEs: Neutropenia (grade 3, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/26214085/
100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Co-administed with:: Amrubicin(35 mg/m2; Days 1-3) Sources: https://pubmed.ncbi.nlm.nih.gov/26214085/	unhealthy, Median age 62 years n = 3 Health Status: unhealthy Condition: nonsmall cell lung cance Age Group: Median age 62 years Sex: M+F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/26214085/	Other AEs: Neutropenia, Neutropenia... Other AEs: Neutropenia (grade 3, 33.3%) Neutropenia (grade 4, 66.7%) Leukopenia (grade 3, 33.3%) Leukopenia (grade 4, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/26214085/
150 mg 1 times / day multiple, oral Recommended Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Co-administed with:: Amrubicin(30 mg/m2; Days 1-3) Sources: https://pubmed.ncbi.nlm.nih.gov/26214085/	unhealthy, Median age 62 years n = 3 Health Status: unhealthy Condition: nonsmall cell lung cance Age Group: Median age 62 years Sex: M+F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/26214085/	Disc. AE: Leukopenia... Other AEs: Erysipelas, Leukopenia... AEs leading to discontinuation/dose reduction: Leukopenia (grade 3, 33.3%) Other AEs: Erysipelas (grade 3, 33.3%) Leukopenia (grade 4, 33.3%) Neutropenia (grade 3, 33.3%) Neutropenia (grade 4, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/26214085/
150 mg 1 times / day multiple, oral Recommended Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_medr.PDF https://www.ema.europa.eu/en/documents/scientific-discussion/tarceva-epar-scientific-discussion_en.pdf	unhealthy, Median age 62 years n = 485 Health Status: unhealthy Condition: nonsmall cell lung cance Age Group: Median age 62 years Sex: M+F Population Size: 485 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_medr.PDF https://www.ema.europa.eu/en/documents/scientific-discussion/tarceva-epar-scientific-discussion_en.pdf	Disc. AE: Rash, Diarrhea... Other AEs: Rash, Pruritus... AEs leading to discontinuation/dose reduction: Rash (10%) Diarrhea (4%) Rash (7%) Diarrhea (2%) Other AEs: Rash (grade 3, 8%) Pruritus (grade 3, <1%) Diarrhea (grade 3, 6%) Nausea (grade 3, 3%) Vomiting (grade 3, 2%) Stomatitis (grade 3, <1%) Constipation (grade 3, 1%) Abdominal pain (grade 3, 2%) Fatigue (grade 3, 14%) Chest pain (grade 3, 4%) Dyspnea (grade 3, 17%) Cough (grade 3, 4%) Hemoptysis (grade 3, 1%) Anorexia (grade 3, 8%) Headache (grade 3, 1%) Neuropathy (grade 3, 3%) Bone pain (grade 3, 3%) Infection (grade 3, 4%) Conjunctivitis (grade 3, <1%) Insomnia (grade 3, <1%) Rash (grade 4, <1%) Diarrhea (grade 4, <1%) Anorexia (grade 4, 1%) Fatigue (grade 4, 4%) Dyspnea (grade 4, 11%) Vomiting (grade 4, <1%) Abdominal pain (grade 4, <1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_medr.PDF https://www.ema.europa.eu/en/documents/scientific-discussion/tarceva-epar-scientific-discussion_en.pdf
150 mg 1 times / day multiple, oral Recommended Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_medr.PDF https://www.ema.europa.eu/en/documents/scientific-discussion/tarceva-epar-scientific-discussion_en.pdf	unhealthy, Median age 62 years n = 485 Health Status: unhealthy Condition: nonsmall cell lung cance Age Group: Median age 62 years Sex: M+F Population Size: 485 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_medr.PDF https://www.ema.europa.eu/en/documents/scientific-discussion/tarceva-epar-scientific-discussion_en.pdf	Disc. AE: Diarrhoea, Rash... AEs leading to discontinuation/dose reduction: Diarrhoea (1%) Rash (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_medr.PDF https://www.ema.europa.eu/en/documents/scientific-discussion/tarceva-epar-scientific-discussion_en.pdf
2000 mg 1 times / week multiple, oral Highest studied dose Dose: 2000 mg, 1 times / week Route: oral Route: multiple Dose: 2000 mg, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/16878326/	unhealthy, Median age 63 years n = 19 Health Status: unhealthy Condition: nonsmall cell lung cance Age Group: Median age 63 years Sex: M+F Population Size: 19 Sources: https://pubmed.ncbi.nlm.nih.gov/16878326/	Other AEs: Fatigue, Dehydration... Other AEs: Fatigue (grade 3, 5.3%) Dehydration (grade 3, 5.3%) Pneumonitis (grade 3, 5.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/16878326/
200 mg 2 times / day multiple, oral Highest studied dose Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/021743lbl.pdf https://www.ema.europa.eu/en/documents/scientific-discussion/tarceva-epar-scientific-discussion_en.pdf	healthy, adult n = 6 Health Status: healthy Age Group: adult Sex: M Population Size: 6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/021743lbl.pdf https://www.ema.europa.eu/en/documents/scientific-discussion/tarceva-epar-scientific-discussion_en.pdf	Disc. AE: Rash... AEs leading to discontinuation/dose reduction: Rash (grade 3, 100%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/021743lbl.pdf https://www.ema.europa.eu/en/documents/scientific-discussion/tarceva-epar-scientific-discussion_en.pdf
1000 mg 1 times / day single, oral Highest studied dose Dose: 1000 mg, 1 times / day Route: oral Route: single Dose: 1000 mg, 1 times / day Sources: https://www.ema.europa.eu/en/documents/scientific-discussion/tarceva-epar-scientific-discussion_en.pdf https://pubmed.ncbi.nlm.nih.gov/11432895/	healthy n = 4 Health Status: healthy Population Size: 4 Sources: https://www.ema.europa.eu/en/documents/scientific-discussion/tarceva-epar-scientific-discussion_en.pdf https://pubmed.ncbi.nlm.nih.gov/11432895/	Other AEs: Erythematous rash... Other AEs: Erythematous rash (grade 1) Sources: https://www.ema.europa.eu/en/documents/scientific-discussion/tarceva-epar-scientific-discussion_en.pdf https://pubmed.ncbi.nlm.nih.gov/11432895/
200 mg 2 times / day multiple, oral Highest studied dose Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/021743lbl.pdf https://www.ema.europa.eu/en/documents/scientific-discussion/tarceva-epar-scientific-discussion_en.pdf	healthy n = 5 Health Status: healthy Population Size: 5 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/021743lbl.pdf https://www.ema.europa.eu/en/documents/scientific-discussion/tarceva-epar-scientific-discussion_en.pdf	Other AEs: Diarrhea, Transaminases increased... Other AEs: Diarrhea Transaminases increased Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/021743lbl.pdf https://www.ema.europa.eu/en/documents/scientific-discussion/tarceva-epar-scientific-discussion_en.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	inhibitor 1767 substrate 1037	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 911 UGT1A1 204 UGT1A9 116 CYP1A1 110 CYP1A2 1524	CYP1A2 1054 CYP2C8 693 CYP1A1 349 CYP1B1 92 CYP2C19 991 CYP3A4/5 85

Drug as perpetrator

Target	Modality	Activity
UGT1A1 254	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=51 Page: -	yes [IC50 0.93 uM]
UGT1A9 121	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=51 Page: -	yes [IC50 31 uM]
CYP1A1 218	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=48 Page: -	yes [IC50 <0.1 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=10 Page: -	yes [Ki 10 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=10 Page: -	yes [Ki 14.7 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=49 Page: -	yes [Ki 20 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=49 Page: -	yes [Ki 35.7 uM]
CYP2C9 1819	inhibitor 3277 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 1737	substrate 3367 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 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=10 Page: -	minor
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=39 Page: -	no
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=39 Page: -	no
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=39 Page: -	no
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=47 Page: -	yes [Km 24 uM]
CYP1A1 349	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=10 Page: -	yes
CYP1B1 92	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-743_Tarceva_biopharmr.PDF#page=10 Page: -	yes
CYP3A4/5 85	substrate 3367 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 1647	inhibitor 1626 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
MolPort	MolPort-003-847-084	https://www.molport.com/shop/molecule-link/MolPort-003-847-084
ZINC	ZINC000001546066	http://zinc15.docking.org/substances/ZINC000001546066
eMolecules	901844	https://www.emolecules.com/cgi-bin/more?vid=901844

PubMed

Title	Date	PubMed
Small-molecule epidermal growth factor receptor tyrosine kinase inhibitors.	2003	14657536
3D-QSAR and docking studies on 4-anilinoquinazoline and 4-anilinoquinoline epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors.	2003 Aug	14703120
Epidermal growth factor receptor tyrosine kinase inhibitors: application in non-small cell lung cancer.	2003 Dec	15025409
Tolerability of gefitinib in patients receiving treatment in everyday clinical practice.	2003 Dec	14661047
Targeting the epidermal growth factor receptor in non-small cell lung cancer.	2003 Dec 1	14676101
For investigational targeted drugs, combination trials pose challenges.	2003 Dec 3	14652234
[Therapeutic implications of epidermal growth factor receptor in lung cancer].	2003 Nov	14763145
[Inhibitors of epidermal growth factor receptor and colorectal cancer].	2003 Nov	14763144
[Targeting of epidermal growth factor receptor and applications in ORL cancer].	2003 Nov	14763143
Identifying predictive and surrogate markers of erlotinib antitumor activity other than rash.	2003 Nov	14682121
Can rash associated with HER1/EGFR inhibition be used as a marker of treatment outcome?	2003 Nov	14682120
Clinical experience with the HER1/EGFR tyrosine kinase inhibitor erlotinib.	2003 Nov	14682119
Erlotinib: preclinical investigations.	2003 Nov	14682118
Targeting the HER1/EGFR receptor to improve outcomes in non-small-cell lung cancer.	2003 Nov	14682117
Epidermal growth factor receptor tyrosine kinase inhibitors in late stage clinical trials.	2003 Nov	14662002
Defining the role of the epidermal growth factor receptor in pancreatic cancer grown in vitro.	2003 Nov	14599602
Pharmacology of oral chemotherapy agents.	2003 Nov-Dec	14705495
Gateways to clinical trials.	2003 Oct	14671684
Distribution and function of EGFR in human tissue and the effect of EGFR tyrosine kinase inhibition.	2003 Sep-Oct	14666659
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
Gateways to clinical trials.	2004 Apr	15148527
Epidermal growth factor receptor inhibitors for the treatment of colorectal cancer: a promise fulfilled?	2004 Apr	15134356
Epidermal growth factor receptor tyrosine kinase inhibitors: evolving role in the treatment of solid tumors.	2004 Apr	15108418
Rationale and clinical validation of epidermal growth factor receptor as a target in the treatment of head and neck cancer.	2004 Apr	15057134
Identification of epidermal growth factor receptor-derived peptides immunogenic for HLA-A2(+) cancer patients.	2004 Apr 19	15083186
Novel treatments in non-small cell lung cancer.	2004 Feb	15005292
Gefitinib ('Iressa', ZD1839) and new epidermal growth factor receptor inhibitors.	2004 Feb 9	14760365
Lung cancer: looking ahead in 2004.	2004 Jan	14967070
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 Jan 1	14701768
Synthesis and SAR of potent EGFR/erbB2 dual inhibitors.	2004 Jan 5	14684309
Gateways to clinical trials.	2004 Jan-Feb	14988742
Emerging treatments in oncology: focus on tyrosine kinase (erbB) receptor inhibitors.	2004 Jan-Feb	14965154
Benzamides and benzamidines as specific inhibitors of epidermal growth factor receptor and v-Src protein tyrosine kinases.	2004 Jul 1	15186837
Targeting non-small cell lung cancer with epidermal growth factor tyrosine kinase inhibitors: where do we stand, where do we go.	2004 Jun	15182824
EGFR inhibitors square off at ASCO.	2004 Jun	15175668
Antitumor activity of erlotinib (OSI-774, Tarceva) alone or in combination in human non-small cell lung cancer tumor xenograft models.	2004 Jun	15166626
Epidermal growth factor receptor tyrosine kinase inhibitors.	2004 Jun 14	15150574
The role of erlotinib (Tarceva, OSI 774) in the treatment of non-small cell lung cancer.	2004 Jun 15	15217965
The role of EGFR inhibitors in nonsmall cell lung cancer.	2004 Mar	15075904
[Bronchioloalveolar carcinoma (BAC)].	2004 Mar	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 Mar	15035290
Emerging role of epidermal growth factor receptor inhibition in therapy for advanced malignancy: focus on NSCLC.	2004 Mar 1	14967461
The HER receptor family: a rich target for therapeutic development.	2004 Mar 1	14967453
Current data and ongoing trials in patients with recurrent non-small-cell lung cancer.	2004 May	15217532
[Lung cancer: molecular targeting therapy].	2004 May	15168452
New cytotoxic and molecular-targeted therapies of head and neck tumors.	2004 May	15069317
Combination treatment of glioblastoma multiforme cell lines with the anti-malarial artesunate and the epidermal growth factor receptor tyrosine kinase inhibitor OSI-774.	2004 May 1	15081868

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

Name

Type

Language

ERLOTINIB

Official 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

CP-358,774

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C2167