AFATINIB

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H25ClFN5O3
Molecular Weight	485.938
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(C)C\C=C\C(=O)NC1=CC2=C(NC3=CC(Cl)=C(F)C=C3)N=CN=C2C=C1O[C@H]4CCOC4

InChI

InChIKey=ULXXDDBFHOBEHA-CWDCEQMOSA-N

InChI=1S/C24H25ClFN5O3/c1-31(2)8-3-4-23(32)30-21-11-17-20(12-22(21)34-16-7-9-33-13-16)27-14-28-24(17)29-15-5-6-19(26)18(25)10-15/h3-6,10-12,14,16H,7-9,13H2,1-2H3,(H,30,32)(H,27,28,29)/b4-3+/t16-/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/201292s009lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000PharmR.pdf

Afatinib is a anilino-quinazoline derivative and irreversible antagonist of the receptor tyrosine kinase epidermal growth factor receptor family, with antineoplastic activity. Afatinib selectively and covalently binds to and inhibits the epidermal growth factor receptors 1 (ErbB1; EGFR), 2 (ErbB2; HER2), and 4 (ErbB4; HER4), and certain EGFR mutants, including those caused by EGFR exon 19 deletion mutations or exon 21 (L858R) mutations. This may result in the inhibition of tumor growth and angiogenesis in tumor cells overexpressing these kinases. Additionally, afatinib inhibits the EGFR T790M gatekeeper mutation which is resistant to treatment with first-generation EGFR inhibitors. EGFR, HER2 and HER4 are RTKs that belong to the EGFR superfamily; they play major roles in both tumor cell proliferation and tumor vascularization and are overexpressed in many cancer cell types. Afatinib is a substrate and an inhibitor of P-gp and of the transporter BCRP. Co-administration of P-gp inhibitors can increase afatinib exposure while co-administration of chronic Pgp inducers can decrease afatinib exposure.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Epidermal growth factor receptor 49 Target ID: P00533\|\|\|Q9GZX1 Gene ID: 1956.0 Gene Symbol: EGFR Target Organism: Homo sapiens (Human) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/201292s009lbl.pdf	Antagonist 2849	0.5 nM [IC50]
Receptor tyrosine-protein kinase erbB-2 6 Target ID: P04626 Gene ID: 2064.0 Gene Symbol: ERBB2 Target Organism: Homo sapiens (Human) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/201292s009lbl.pdf	Antagonist 2849	14.0 nM [IC50]
Receptor tyrosine-protein kinase erbB-4 5 Target ID: Q15303 Gene ID: 2066.0 Gene Symbol: ERBB4 Target Organism: Homo sapiens (Human) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/201292s009lbl.pdf	Antagonist 2849	0.7 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Non-small cell lung cancer 211 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/201292s009lbl.pdf	Primary		Approved 8583	GILOTRIF Approved Use Indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test Launch Date 2013

C_max

Value	Dose	Co-administered	Analyte	Population
33.7 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24906422	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		AFATINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
30.7 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24906422	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		AFATINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
42.7 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29337963	40 mg 1 times / day steady-state, oral dose: 40 mg route of administration: Oral experiment type: STEADY-STATE co-administered: VINORELBINE	VINORELBINE	AFATINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
886 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24906422	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		AFATINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
956 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24906422	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		AFATINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
683 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29337963	40 mg 1 times / day steady-state, oral dose: 40 mg route of administration: Oral experiment type: STEADY-STATE co-administered: VINORELBINE	VINORELBINE	AFATINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
37 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/201292s014lbl.pdf	40 mg 1 times / day multiple, oral dose: 40 mg route of administration: Oral experiment type: MULTIPLE co-administered:	AFATINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
74.9 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24906422	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	AFATINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
60.3 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24906422	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	AFATINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/201292s014lbl.pdf			AFATINIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
50 mg 1 times / day multiple, oral Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://www.ema.europa.eu/en/documents/assessment-report/giotrif-epar-public-assessment-report_en.pdf https://pubmed.ncbi.nlm.nih.gov/22452896/	unhealthy, 32 to 82 years Health Status: unhealthy Age Group: 32 to 82 years Sex: M+F Sources: https://www.ema.europa.eu/en/documents/assessment-report/giotrif-epar-public-assessment-report_en.pdf https://pubmed.ncbi.nlm.nih.gov/22452896/	Other AEs: Diarrhoea, Rash... Other AEs: Diarrhoea (84.6%) Rash (72.3%) Dermatitis acneiform (13.6%) Stomatitis (58.2%) Nail disorder (38.5%) Decreased appetite (20.8%) Nausea (18.7%) Pruritus (17.7%) Epistaxis (14.6%) Dry skin (14.4%) Fatigue (14.4%) Vomiting (13.3%) Eye disorders NEC (9.2%) Palmar-plantar erythrodysaesthesia syndrome (7.7%) Diarrhoea (grade 3, 38.7%) Rash (grade 3, 13.3%) Dermatitis acneiform (grade 3, 1.3%) Stomatitis (grade 3, 2.8%) Nail disorder (grade 3, 4.9%) Decreased appetite (grade 3, 2.8%) Nausea (grade 3, 1.3%) Pruritus (grade 3, 0.3%) Dry skin (grade 3, 0.3%) Fatigue (grade 3, 3.1%) Vomiting (grade 3, 1.5%) Eye disorders NEC (grade 3, 0.5%) Palmar-plantar erythrodysaesthesia syndrome (grade 3, 1.3%) Diarrhoea (grade 4, 1%) Sources: https://www.ema.europa.eu/en/documents/assessment-report/giotrif-epar-public-assessment-report_en.pdf https://pubmed.ncbi.nlm.nih.gov/22452896/
50 mg 1 times / day multiple, oral Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://www.ema.europa.eu/en/documents/assessment-report/giotrif-epar-public-assessment-report_en.pdf https://pubmed.ncbi.nlm.nih.gov/22452896/	unhealthy, 32 to 82 years Health Status: unhealthy Age Group: 32 to 82 years Sex: M+F Sources: https://www.ema.europa.eu/en/documents/assessment-report/giotrif-epar-public-assessment-report_en.pdf https://pubmed.ncbi.nlm.nih.gov/22452896/	Other AEs: ALT increased, AST increased... Other AEs: ALT increased (3.8%) AST increased (2.8%) Alkaline phosphatase increased (0.8%) Bilirubin increased (0.3%) GGT increased (0.3%) Hyperbilirubinaemia (1%) Hypoalbuminaemia (1.5%) Acute hepatic failure (0.3%) Anorectal varices (0.3%) Cytolytic hepatitis (0.3%) Hepatic pain (0.3%) Hepatitis acute (0.3%) Sources: https://www.ema.europa.eu/en/documents/assessment-report/giotrif-epar-public-assessment-report_en.pdf https://pubmed.ncbi.nlm.nih.gov/22452896/
360 mg 1 times / day single, oral Dose: 360 mg, 1 times / day Route: oral Route: single Dose: 360 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/201292s000lbl.pdf	healthy, adolescents Health Status: healthy Age Group: adolescents Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/201292s000lbl.pdf	Other AEs: Nausea, Vomiting... Other AEs: Nausea Vomiting Asthenia Dizziness Headache Abdominal pain Amylase increased Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/201292s000lbl.pdf
100 mg 1 times / day multiple, oral Highest studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18026190/	unhealthy, median age 58 years Health Status: unhealthy Age Group: median age 58 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18026190/	DLT: Skin rash, Diarrhoea... Dose limiting toxicities: Skin rash (grade 3, 50%) Diarrhoea (grade 3, 50%) Sources: https://pubmed.ncbi.nlm.nih.gov/18026190/
70 mg 1 times / day multiple, oral MTD Dose: 70 mg, 1 times / day Route: oral Route: multiple Dose: 70 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18026190/	unhealthy, median age 58 years Health Status: unhealthy Age Group: median age 58 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18026190/	DLT: Fatigue, ALT increased... Dose limiting toxicities: Fatigue (grade 3, 5.6%) ALT increased (grade 3, 5.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/18026190/
70 mg 1 times / day multiple, oral Dose: 70 mg, 1 times / day Route: oral Route: multiple Dose: 70 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18026190/	unhealthy, median age 58 years Health Status: unhealthy Age Group: median age 58 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18026190/	DLT: Diarrhoea... Dose limiting toxicities: Diarrhoea (grade 3, 11.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/18026190/
85 mg 1 times / day multiple, oral Dose: 85 mg, 1 times / day Route: oral Route: multiple Dose: 85 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18026190/	unhealthy, median age 58 years Health Status: unhealthy Age Group: median age 58 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18026190/	DLT: Diarrhoea, Diarrhoea... Dose limiting toxicities: Diarrhoea (grade 3, 16.7%) Diarrhoea (grade 2, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/18026190/
40 mg 1 times / day multiple, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000MedR.pdf https://pubmed.ncbi.nlm.nih.gov/23816960/	unhealthy, median age 61.5 years Health Status: unhealthy Age Group: median age 61.5 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000MedR.pdf https://pubmed.ncbi.nlm.nih.gov/23816960/	Other AEs: Diarrhea, Stomatitis... Other AEs: Diarrhea (grade 3, 15%) Stomatitis (grade 3, 8%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000MedR.pdf https://pubmed.ncbi.nlm.nih.gov/23816960/
40 mg 1 times / day multiple, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000MedR.pdf https://pubmed.ncbi.nlm.nih.gov/23816960/	unhealthy, median age 61.5 years Health Status: unhealthy Age Group: median age 61.5 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000MedR.pdf https://pubmed.ncbi.nlm.nih.gov/23816960/	Disc. AE: Diarrhea, Paronychia... AEs leading to discontinuation/dose reduction: Diarrhea (1.3%) Paronychia (0.9%) Interstitial lung disease (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000MedR.pdf https://pubmed.ncbi.nlm.nih.gov/23816960/
40 mg 1 times / day multiple, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000MedR.pdf https://www.boehringer-ingelheim.ca/sites/ca/files/documents/giotrifpmen.pdf	unhealthy, median age 61.5 years Health Status: unhealthy Age Group: median age 61.5 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000MedR.pdf https://www.boehringer-ingelheim.ca/sites/ca/files/documents/giotrifpmen.pdf	Other AEs: Weight decreased, Nausea... Other AEs: Weight decreased (grade 3, 1%) Nausea (grade 3, 1%) Vomiting (grade 3, 4%) Dermatitis acneiform (grade 3, 3%) Hypokalaemia (grade 3, 2%) ALT increased (grade 3, 2%) AST increased (grade 3, 2%) Stomatitis (grade 4, <1%) Hypokalaemia (grade 4, 2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000MedR.pdf https://www.boehringer-ingelheim.ca/sites/ca/files/documents/giotrifpmen.pdf
40 mg 1 times / day multiple, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000MedR.pdf	unhealthy, median age 61.5 years Health Status: unhealthy Age Group: median age 61.5 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000MedR.pdf	Other AEs: Rash, Paronychia... Other AEs: Rash (grade 3, 16%) Paronychia (grade 3, 11%) Cystitis (grade 3, 1%) Decreased appetite (grade 3, 4%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000MedR.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252 inducer 1087	inhibitor 2438 inducer 440	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741 BCRP 910 CYP1A 70 CYP2A6 879 CYP2B6 926 CYP2C8 1057 CYP2C19 2057 CYP2E1 1060 CYP4A11 21	P-gp 2052 FMO3 77 BCRP 697	CYP1A2 832 CYP2B6 669 CYP2C8 198 CYP2C19 329

Drug as perpetrator

Target	Modality	Activity
CYP1A 122	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=41 Page: -	no
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=42 Page: -	no
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=41 Page: -	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=42 Page: -	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=41 Page: -	no
CYP2C19 2141	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=42 Page: -	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=41 Page: -	no
CYP2C8 1117	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=42 Page: -	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=41 Page: -	no
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=42 Page: -	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=41 Page: -	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=41 Page: -	no
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=41 Page: -	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=42 Page: -	no
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=41 Page: -	no
CYP4A11 25	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=41 Page: -	no
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=44 Page: -	yes [IC50 0.75 uM]
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=15 Page: -	yes [Ki 3.4 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=32 Page: -	minor
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=15 Page: -	yes [Km 30 uM]	yes (co-administration study) Comment: Afatinib is a substrate and inhibitor (Ki=3.4 μM) for P-gp transporter and exposure to afatinib was changed when it was administered with a P-gp inhibitor, ritonavir (AUC increased by 48%) or with a P-gp inducer, rifampicin (AUC decreased by 34%). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=15 Page: -
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=44 Page: -	yes
FMO3 77	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000ClinPharmR.pdf#page=32 Page: -	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/201292Orig1s000PharmR.pdf#page=5 Page: -

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:61390	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:61390
ChemicalBook	CB12470923	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB12470923
ChemicalBook	CB62507657	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB62507657
MolPort	MolPort-009-679-394	https://www.molport.com/shop/molecule-link/MolPort-009-679-394
Selleck Chemicals	BIBW2992	http://www.selleckchem.com/products/BIBW2992.html
ZINC	ZINC000003976838	http://zinc15.docking.org/substances/ZINC000003976838

PubMed

Title	Date	PubMed
		252160239
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.	2010 Nov 24	21095574
Phase I trial of the irreversible EGFR and HER2 kinase inhibitor BIBW 2992 in patients with advanced solid tumors.	2010 Sep 1	20679611
Irreversible EGFR inhibitor EKB-569 targets low-LET γ-radiation-triggered rel orchestration and potentiates cell death in squamous cell carcinoma.	2011	22242139
Afatinib (BIBW 2992) development in non-small-cell lung cancer.	2011 Jul	21732753
Cysteine mapping in conformationally distinct kinase nucleotide binding sites: application to the design of selective covalent inhibitors.	2011 Mar 10	21322567
Genotype-driven therapies for non-small cell lung cancer: focus on EGFR, KRAS and ALK gene abnormalities.	2011 May	21904575
Comprehensive analysis of kinase inhibitor selectivity.	2011 Oct 30	22037378

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose is 40 mg orally once daily.

Route of Administration: Oral

In Vitro Use Guide

In cellular in vitro assays, afatinib was able to inhibit phosphorylation and/or proliferation of multiple cell lines representing models of overexpression of wild type EGFR, constitutively active HER2, and EGFR exon 19 deletion mutations, including an exon 19/T790M double mutant. Concentrations of afatinib required for activity in these models ranged from approximately 10 to 100 nM; effects on exon 19/T790M double mutants typically occurred at the high end of this range.

Name

Type

Language

TOVOK

Preferred Name

English

AFATINIB

Official Name

English

Afatinib [WHO-DD]

Common Name

English

AFATINIB [MI]

Common Name

English

AFATINIB [USAN]

Common Name

English

BIBW 2992

Common Name

English

AFATINIB [VANDF]

Common Name

English

(2E)-N-(4-(3-CHLORO-4-FLUOROANILINO)-7-(((3S)-OXOLAN-3-YL)OXY)QUINOXAZOLIN-6-YL)-4-(DIMETHYLAMINO)BUT-2-ENAMIDE

Common Name

English

TOMTOVOK

Brand Name

English

BIBW2992

Code

English

afatinib [INN]

Common Name

English

BIBW-2992

Code

English

AFATINIB [MART.]

Common Name

English

NSC-750691

Code

English

2-BUTENAMIDE, N-(4-((3-CHLORO-4-FLUOROPHENYL)AMINO)-7-(((3S)-TETRAHYDRO-3-FURANYL)OXY)- 6-QUINAZOLINYL)-4-(DIMETHYLAMINO)-, (2E)-

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175605