neratinib   Click here for help

GtoPdb Ligand ID: 5686

Synonyms: HKI 272 | HKI-272 | Nerlynx®
Approved drug
neratinib is an approved drug (FDA (2017), EMA (2018))
Compound class: Synthetic organic
Comment: Neratinib is an irreversible inhibitor of the receptor tyrosine kinase (RTK), ErbB2 [4]. It also inhibits the related RTK, EGFR.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Click here for structure editor
Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 7
Hydrogen bond donors 2
Rotatable bonds 12
Topological polar surface area 112.4
Molecular weight 556.2
XLogP 3.87
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES CCOc1cc2ncc(c(c2cc1NC(=O)C=CCN(C)C)Nc1ccc(c(c1)Cl)OCc1ccccn1)C#N
Isomeric SMILES CCOc1cc2ncc(c(c2cc1NC(=O)/C=C/CN(C)C)Nc1ccc(c(c1)Cl)OCc1ccccn1)C#N
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
No information available.
Summary of Clinical Use Click here for help
In July 2017 the FDA granted marketing approval for neratinib's use as an extended adjuvant treatment of early-stage, HER2-positive breast cancer, in patients previously treated with drugs including trastuzumab. Neratinib therapy lowers the risk of cancer recurrence in this patient group. EMA approval followed in August 2018. Visit ClinicalTrials.gov to view currently registered neratinib trials.

Neratinib is one of the drugs being assessed in a new type of clinical trial, called adaptive trials being performed as part of the public/private partnership I-SPY trials which aim to streamline drug testing by targeting drugs to patients by assessing their cancer-specific genetic markers, so that the most useful drugs are used in those patients most likely to respond to them. The I-SPY trials are 'adaptive' in the sense that early data from current patients is used to guide treatment regimens for the next patients entering the trial. It is hoped that this more thoughtful and flexible trial framework will expedite identification of drugs and drug combinations with the most positive outcome in those patients in most need. Positive results from an I-SPY 2 trial (Phase 2) of neratinib in HER2-positive, hormone-receptor-negative breast cancer were reported in 2016 [3].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01808573 A Study of Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in Patients With HER2+ Metastatic Breast Cancer Who Have Received Two or More Prior HER2 Directed Regimens in the Metastatic Setting Phase 3 Interventional Puma Biotechnology, Inc. Neratinib + capecitabine was FDA approved in February 2020 for patients indicated by results from this trial. This drug combination has emerged as an effective regimen for the management of HER2+ve metastatic breast cancer patients with brain metastasis. 2
External links Click here for help
For extended ADME data see the following:

Drugs.com
European Medicines Agency (EMA)