Neratinib

Drug information

CovInDB Drug
DB11828
Name
Neratinib
Molecular Formula
C30H29ClN6O3
Molecular Weight
556.2 g/mol
Description
Neratinib was approved in July 2017 for use as an extended adjuvant therapy in Human Epidermal Growth Factor Receptor 2 (HER2) positive breast cancer. Approval was granted to Puma Biotechnology Inc. for the tradename Nerlynx. Neratinib is currently under investigation for use in many other forms of cancer.
Status
approved, investigational
Structure
2D structure
  Warhead   Similar Compounds
Indication
For use as an extended adjuvant treatment in adult patients with early stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.
Mechanism of action

Neratinib binds to and irreversibly inhibits EGFR, HER2, and HER4. This prevents auotphoshorylation of tyrosine residues on the receptor and reduces oncogenic signalling through the mitogen-activated protein kinase and Akt pathways.

IUPAC Name
(E)-N-[4-[3-chloro-4-(2-pyridylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide
InChI
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+
InChI Key
JWNPDZNEKVCWMY-VQHVLOKHSA-N
Canonical SMILES
CCOC1=C(NC(=O)\C=C\CN(C)C)C=C2C(NC3=CC=C(OCC4=CC=CC=N4)C(Cl)=C3)=C(C=NC2=C1)C#N
Reference
DrugBank



Covalent Inhibition


Warhead
Micheal Acceptor
Target

Epidermal growth factor receptor   [ UniProt: P00533 ]

Site
CYS-797
Inhibition Mechanism

Neratinib: First Global Approval




3D Structure

  Show Warhead


Calculated Properties

logP

4.72

Computed by ALOGPS

logS

-4.92

Computed by ALOGPS

Heavy Atom Count

40

Computed by RDKit

Ring Count

4

Computed by RDKit

Hydrogen Bond Acceptor Count

8

Computed by RDKit

Hydrogen Bond Donor Count

2

Computed by RDKit

Rotatable Bond Count

11

Computed by RDKit

Topological Polar Surface Area

112.4 Å2

Computed by RDKit




Similar compounds in Virtual Screening library

  Download

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Similar Natural compounds

No similar natural compounds found for this drug.