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Details

Stereochemistry ABSOLUTE
Molecular Formula C24H25ClFN5O3.2C4H4O4
Molecular Weight 718.083
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 3
Charge 0

SHOW SMILES / InChI
Structure of AFATINIB DIMALEATE

SMILES

OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.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=USNRYVNRPYXCSP-JUGPPOIOSA-N
InChI=1S/C24H25ClFN5O3.2C4H4O4/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;2*5-3(6)1-2-4(7)8/h3-6,10-12,14,16H,7-9,13H2,1-2H3,(H,30,32)(H,27,28,29);2*1-2H,(H,5,6)(H,7,8)/b4-3+;2*2-1-/t16-;;/m0../s1

HIDE SMILES / InChI

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

Molecular Formula C4H4O4
Molecular Weight 116.0722
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description

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

Approval Year

PubMed

PubMed

TitleDatePubMed
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
2010 Nov 24
Phase I trial of the irreversible EGFR and HER2 kinase inhibitor BIBW 2992 in patients with advanced solid tumors.
2010 Sep 1
Irreversible EGFR inhibitor EKB-569 targets low-LET γ-radiation-triggered rel orchestration and potentiates cell death in squamous cell carcinoma.
2011
Afatinib (BIBW 2992) development in non-small-cell lung cancer.
2011 Jul
Cysteine mapping in conformationally distinct kinase nucleotide binding sites: application to the design of selective covalent inhibitors.
2011 Mar 10
Genotype-driven therapies for non-small cell lung cancer: focus on EGFR, KRAS and ALK gene abnormalities.
2011 May
Comprehensive analysis of kinase inhibitor selectivity.
2011 Oct 30
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.
Substance Class Chemical
Created
by admin
on Mon Oct 21 23:46:44 UTC 2019
Edited
by admin
on Mon Oct 21 23:46:44 UTC 2019
Record UNII
V1T5K7RZ0B
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AFATINIB DIMALEATE
MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN  
Official Name English
AFATINIB DIMALEATE [MI]
Common Name English
BIBW-2992MA2
Code English
AFATINIB DIMALEATE [USAN]
Common Name English
BIBW-2992 MA2
Code English
GILOTRIF
Brand Name English
2-BUTENAMIDE, N-(4-((3-CHLORO-4-FLUOROPHENYL)AMINO)-7-(((3S)-TETRAHYDRO-3-FURANYL)OXY)-6-QUINAZOLINYL)-4-(DIMETHYLAMINO)-, (2E)-, (2Z)-2-BUTENEDIOATE (1:2)
Common Name English
BIBW2992 MA2
Code English
(2E)-N-(4-((3-CHLORO-4-FLUOROPHENYL)AMINO)-7-(((3S)-TETRAHYDROFURAN-3-YL)OXY)QUINAZOLIN- 6-YL)-4-(DIMETHYLAMINO)BUT-2-ENAMIDE BIS(HYDROGEN (2Z)-BUT-2-ENEDIOATE)
Common Name English
AFATINIB MALEATE
JAN  
JAN  
Official Name English
BIBW-2992-MA2
Code English
AFATINIB DIMALEATE [VANDF]
Common Name English
BIBW2992-MA2
Code English
AFATINIB DIMALEATE [ORANGE BOOK]
Common Name English
AFATINIB DIMALEATE [WHO-DD]
Common Name English
GIOTRIF
Brand Name English
AFATINIB MALEATE [JAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Mon Oct 21 23:46:44 UTC 2019 , Edited by admin on Mon Oct 21 23:46:44 UTC 2019
NCI_THESAURUS C2167
Created by admin on Mon Oct 21 23:46:44 UTC 2019 , Edited by admin on Mon Oct 21 23:46:44 UTC 2019
Code System Code Type Description
CAS
850140-73-7
Created by admin on Mon Oct 21 23:46:44 UTC 2019 , Edited by admin on Mon Oct 21 23:46:44 UTC 2019
PRIMARY
MERCK INDEX
M1439
Created by admin on Mon Oct 21 23:46:44 UTC 2019 , Edited by admin on Mon Oct 21 23:46:44 UTC 2019
PRIMARY Merck Index
NCI_THESAURUS
C97273
Created by admin on Mon Oct 21 23:46:44 UTC 2019 , Edited by admin on Mon Oct 21 23:46:44 UTC 2019
PRIMARY
JAPANESE REVIEW
GIOTRIF
Created by admin on Mon Oct 21 23:46:44 UTC 2019 , Edited by admin on Mon Oct 21 23:46:44 UTC 2019
PRIMARY APPROVED JANUARY 2014
RXCUI
1430441
Created by admin on Mon Oct 21 23:46:44 UTC 2019 , Edited by admin on Mon Oct 21 23:46:44 UTC 2019
PRIMARY RxNorm
ChEMBL
CHEMBL1173655
Created by admin on Mon Oct 21 23:46:44 UTC 2019 , Edited by admin on Mon Oct 21 23:46:44 UTC 2019
PRIMARY
EVMPD
SUB121316
Created by admin on Mon Oct 21 23:46:44 UTC 2019 , Edited by admin on Mon Oct 21 23:46:44 UTC 2019
PRIMARY
CAS
936631-70-8
Created by admin on Mon Oct 21 23:46:44 UTC 2019 , Edited by admin on Mon Oct 21 23:46:44 UTC 2019
NON-SPECIFIC STEREOCHEMISTRY
PUBCHEM
15606394
Created by admin on Mon Oct 21 23:46:44 UTC 2019 , Edited by admin on Mon Oct 21 23:46:44 UTC 2019
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY