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Details

Stereochemistry ACHIRAL
Molecular Formula C30H29ClN6O3
Molecular Weight 557.043
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of NERATINIB

SMILES

CCOC1=CC2=C(C=C1NC(=O)\C=C\CN(C)C)C(NC3=CC(Cl)=C(OCC4=CC=CC=N4)C=C3)=C(C=N2)C#N

InChI

InChIKey=JWNPDZNEKVCWMY-VQHVLOKHSA-N
InChI=1S/C30H29ClN6O3/c1-4-39-28-16-25-23(15-26(28)36-29(38)9-7-13-37(2)3)30(20(17-32)18-34-25)35-21-10-11-27(24(31)14-21)40-19-22-8-5-6-12-33-22/h5-12,14-16,18H,4,13,19H2,1-3H3,(H,34,35)(H,36,38)/b9-7+

HIDE SMILES / InChI

Description

Neratinib (HKI-272) is a pan-HER inhibitor, this irreversible tyrosine kinase inhibitor binds and inhibits the tyrosine kinase activity of epidermal growth factor receptors, EGFR (or HER1), HER2 and HER4, which leads to reduced phosphorylation and activation of downstream signaling pathways. Neratinib is a modified form of the discontinued compound pelitinib, and was originally being develoAdditionally, phase II development of oral neratinib as a neoadjuvant therapy for breast cancer, as a second-line therapy for non-small cell lung cancer, and for other solid tumours is also in progress in numerous countries worldwide. ped by Wyeth (later Pfizer). Oral neratinib is awaiting approval as an extended adjuvant therapy for breast cancer in the EU and in the US. Blocking HER2 function by a small molecule kinase inhibitor, such as neratinib, represents an attractive alternate strategy for the growth inhibition of HER2-positive tumours.

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
2010 Nov 24
Comprehensive analysis of kinase inhibitor selectivity.
2011 Oct 30
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
2013 Nov
Patents

Sample Use Guides

In Vivo Use Guide
Patients who received 40, 80, or 120 mg experienced no dose-limiting toxicities. The study determined the maximum tolerated dose at 320 mg, with 240 mg being the therapeutic dose.
Route of Administration: Oral
In Vitro Use Guide
both very low (10 nM) and physiologically attainable concentrations of neratinib (133 nM) significantly inhibited the autophosphorylation of HER2/neu and activation of S6 in primary carcinosarcoma cells
Name Type Language
NERATINIB
INN   MART.   MI   USAN   WHO-DD  
INN   USAN  
Official Name English
2-BUTENAMIDE, N-(4-((3-CHLORO-4-(2-PYRIDINYLMETHOXY)PHENYL)AMINO)-3-CYANO-7-ETHOXY-6-QUINOLINYL)-4-(DIMETHYLAMINO)-, (2E)-
Systematic Name English
HKI-272
Code English
CDP-820
Code English
NERATINIB [WHO-DD]
Common Name English
NERATINIB [MART.]
Common Name English
NERATINIB [MI]
Common Name English
NERATINIB [USAN]
Common Name English
NERATINIB [INN]
Common Name English
(2E)-N-(4-((3-CHLORO-4-((PYRIDIN-2-YL)METHOXY)PHENYL)AMINO)-3-CYANO-7-ETHOXYQUINOLIN-6-YL)-4-(DIMETHYLAMINO)BUT-2-ENAMIDE
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C1967
Created by admin on Mon Oct 21 23:45:06 UTC 2019 , Edited by admin on Mon Oct 21 23:45:06 UTC 2019
NCI_THESAURUS C129825
Created by admin on Mon Oct 21 23:45:06 UTC 2019 , Edited by admin on Mon Oct 21 23:45:06 UTC 2019
WHO-ATC L01XE45
Created by admin on Mon Oct 21 23:45:06 UTC 2019 , Edited by admin on Mon Oct 21 23:45:06 UTC 2019
NDF-RT N0000175605
Created by admin on Mon Oct 21 23:45:06 UTC 2019 , Edited by admin on Mon Oct 21 23:45:06 UTC 2019
Code System Code Type Description
WIKIPEDIA
NERATINIB
Created by admin on Mon Oct 21 23:45:06 UTC 2019 , Edited by admin on Mon Oct 21 23:45:06 UTC 2019
PRIMARY
ChEMBL
CHEMBL180022
Created by admin on Mon Oct 21 23:45:06 UTC 2019 , Edited by admin on Mon Oct 21 23:45:06 UTC 2019
PRIMARY
PUBCHEM
9915743
Created by admin on Mon Oct 21 23:45:06 UTC 2019 , Edited by admin on Mon Oct 21 23:45:06 UTC 2019
PRIMARY
EVMPD
SUB32232
Created by admin on Mon Oct 21 23:45:06 UTC 2019 , Edited by admin on Mon Oct 21 23:45:06 UTC 2019
PRIMARY
EPA CompTox
698387-09-6
Created by admin on Mon Oct 21 23:45:06 UTC 2019 , Edited by admin on Mon Oct 21 23:45:06 UTC 2019
PRIMARY
INN
8878
Created by admin on Mon Oct 21 23:45:06 UTC 2019 , Edited by admin on Mon Oct 21 23:45:06 UTC 2019
PRIMARY
RXCUI
1940643
Created by admin on Mon Oct 21 23:45:06 UTC 2019 , Edited by admin on Mon Oct 21 23:45:06 UTC 2019
PRIMARY
CAS
698387-09-6
Created by admin on Mon Oct 21 23:45:06 UTC 2019 , Edited by admin on Mon Oct 21 23:45:06 UTC 2019
PRIMARY
NCI_THESAURUS
C49094
Created by admin on Mon Oct 21 23:45:06 UTC 2019 , Edited by admin on Mon Oct 21 23:45:06 UTC 2019
PRIMARY
MERCK INDEX
M7827
Created by admin on Mon Oct 21 23:45:06 UTC 2019 , Edited by admin on Mon Oct 21 23:45:06 UTC 2019
PRIMARY Merck Index