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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2D Structure
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Physico-chemical Properties
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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
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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+
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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 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
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