neratinib Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 5252 698387-09-6

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • neratinib
  • neratinib maleate
  • HKI-272
  • nerlynx
Neratinib is a kinase inhibitor that irreversibly binds to Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), and HER4. In vitro, neratinib reduces EGFR and HER2 autophosphorylation, downstream MAPK and AKT signaling pathways, and showed antitumor activity in EGFR and/or HER2 expressing carcinoma cell lines. Neratinib human metabolites M3, M6, M7 and M11 inhibited the activity of EGFR, HER2 and HER4 in vitro. In vivo, oral administration of neratinib inhibited tumor growth in mouse xenograft models with tumor cell lines expressing HER2 and EGFR.
  • Molecular weight: 557.05
  • Formula: C30H29ClN6O3
  • CLOGP: 5.00
  • LIPINSKI: 1
  • HAC: 9
  • HDO: 2
  • TPSA: 112.40
  • ALOGS: -4.92
  • ROTB: 11

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
Aug. 8, 2018 EMA PUMA BIOTECH INC
July 17, 2017 FDA PUMA BIOTECH INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Diarrhoea 78.63 48.13 25 70 83539 2274451
Hypokalaemia 63.66 48.13 14 81 10640 2347350

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event

Pharmacologic Action:

SourceCodeDescription
ATC L01XE45 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Protein kinase inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000175082 Kinase Inhibitors
FDA MoA N0000185503 P-Glycoprotein Inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
HER2-positive carcinoma of breast indication 427685000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 10.4 acidic
pKa2 8.94 Basic
pKa3 6.11 Basic
pKa4 3.66 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 40MG BASE NERLYNX PUMA BIOTECH N208051 July 17, 2017 RX TABLET ORAL 7982043 Oct. 8, 2025 EXTENDED ADJUVANT TREATMENT OF ADULT PATIENTS WITH EARLY STAGE HER2-OVEREXPRESSED/AMPLIFIED BREAST CANCER, TO FOLLOW ADJUVANT TRASTUZUMAB BASE THERAPY
EQ 40MG BASE NERLYNX PUMA BIOTECH N208051 July 17, 2017 RX TABLET ORAL 10035788 Oct. 15, 2028 EXTENDED ADJUVANT TREATMENT OF ADULT PATIENTS WITH EARLY STAGE HER2-OVEREXPRESSED/AMPLIFIED BREAST CANCER, TO FOLLOW ADJUVANT TRASTUZUMAB BASE THERAPY
EQ 40MG BASE NERLYNX PUMA BIOTECH N208051 July 17, 2017 RX TABLET ORAL 9139558 Oct. 15, 2028 EXTENDED ADJUVANT TREATMENT OF ADULT PATIENTS WITH EARLY STAGE HER2-OVEREXPRESSED/AMPLIFIED BREAST CANCER, TO FOLLOW ADJUVANT TRASTUZUMAB BASE THERAPY
EQ 40MG BASE NERLYNX PUMA BIOTECH N208051 July 17, 2017 RX TABLET ORAL 9630946 Oct. 15, 2028 EXTENDED ADJUVANT TREATMENT OF ADULT PATIENTS WITH EARLY STAGE HER2-OVEREXPRESSED/AMPLIFIED BREAST CANCER, TO FOLLOW ADJUVANT TRASTUZUMAB BASE THERAPY
EQ 40MG BASE NERLYNX PUMA BIOTECH N208051 July 17, 2017 RX TABLET ORAL 9211291 March 24, 2030 EXTENDED ADJUVANT TREATMENT OF ADULT PATIENTS WITH EARLY STAGE HER2-OVEREXPRESSED/AMPLIFIED BREAST CANCER, TO FOLLOW ADJUVANT TRASTUZUMAB BASE THERAPY
EQ 40MG BASE NERLYNX PUMA BIOTECH N208051 July 17, 2017 RX TABLET ORAL 8790708 Nov. 5, 2030 EXTENDED ADJUVANT TREATMENT OF ADULT PATIENTS WITH EARLY STAGE HER2-OVEREXPRESSED/AMPLIFIED BREAST CANCER, TO FOLLOW ADJUVANT TRASTUZUMAB BASE THERAPY
EQ 40MG BASE NERLYNX PUMA BIOTECH N208051 July 17, 2017 RX TABLET ORAL 8518446 Nov. 20, 2030 EXTENDED ADJUVANT TREATMENT OF ADULT PATIENTS WITH EARLY STAGE HER2-OVEREXPRESSED/AMPLIFIED BREAST CANCER, TO FOLLOW ADJUVANT TRASTUZUMAB BASE THERAPY

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 40MG BASE NERLYNX PUMA BIOTECH N208051 July 17, 2017 RX TABLET ORAL July 17, 2022 NEW CHEMICAL ENTITY
EQ 40MG BASE NERLYNX PUMA BIOTECH N208051 July 17, 2017 RX TABLET ORAL Feb. 25, 2023 USE IN COMBINATION WITH CAPECITABINE, FOR THE TREATMENT OF ADULT PATIENTS WITH ADVANCED OR METASTATIC HER2-POSITIVE BREAST CANCER WHO HAVE RECEIVED TWO OR MORE PRIOR ANTI-HER2 BASED REGIMENS IN THE METASTATIC SETTING

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Epidermal growth factor receptor Kinase INHIBITOR IC50 7.04 SCIENTIFIC LITERATURE DRUG LABEL
Receptor tyrosine-protein kinase erbB-2 Kinase INHIBITOR IC50 7.23 SCIENTIFIC LITERATURE DRUG LABEL
Receptor tyrosine-protein kinase erbB-4 Kinase INHIBITOR Kd 8.62 SCIENTIFIC LITERATURE DRUG LABEL
Vascular endothelial growth factor receptor 2 Kinase IC50 6.07 CHEMBL
Tyrosine-protein kinase ABL1 Kinase Kd 5.22 CHEMBL
Macrophage colony-stimulating factor 1 receptor Kinase Kd 6.17 CHEMBL
Tyrosine-protein kinase Fer Kinase Kd 6.29 CHEMBL
Tyrosine-protein kinase Fgr Kinase Kd 5.72 CHEMBL
Cyclin-G-associated kinase Kinase Kd 6.60 CHEMBL
Tyrosine-protein kinase Lck Kinase Kd 6.92 CHEMBL
Proto-oncogene tyrosine-protein kinase Src Kinase Kd 5.39 CHEMBL
Tyrosine-protein kinase receptor Tie-1 Kinase Kd 6.41 CHEMBL
Tyrosine-protein kinase Yes Kinase Kd 6.62 CHEMBL
Serine/threonine-protein kinase D3 Kinase Kd 5.62 CHEMBL
Mitogen-activated protein kinase kinase kinase 4 Kinase Kd 7.41 CHEMBL
Serine/threonine-protein kinase 10 Kinase Kd 7.89 CHEMBL
Cyclin-dependent kinase 16 Kinase Kd 5.64 CHEMBL
Serine/threonine-protein kinase 3 Kinase Kd 7.24 CHEMBL
Serine/threonine-protein kinase 4 Kinase Kd 6.57 CHEMBL
Mitogen-activated protein kinase kinase kinase 12 Kinase Kd 6.43 CHEMBL
Serine/threonine-protein kinase 25 Kinase Kd 7.92 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 5 Kinase Kd 9.19 CHEMBL
Mitogen-activated protein kinase kinase kinase 2 Kinase Kd 6.35 CHEMBL
Insulin receptor-related protein Kinase Kd 5.34 CHEMBL
STE20-like serine/threonine-protein kinase Kinase Kd 7.18 CHEMBL
Maternal embryonic leucine zipper kinase Kinase Kd 5.80 CHEMBL
NUAK family SNF1-like kinase 1 Kinase Kd 5.82 CHEMBL
Microtubule-associated serine/threonine-protein kinase 1 Kinase Kd 5.26 CHEMBL
TRAF2 and NCK-interacting protein kinase Kinase Kd 6.85 CHEMBL
Serine/threonine-protein kinase SIK2 Kinase Kd 5.48 CHEMBL
Serine/threonine-protein kinase 36 Kinase Kd 5.28 CHEMBL
Serine/threonine-protein kinase TAO3 Kinase Kd 5.38 CHEMBL
Serine/threonine-protein kinase D2 Kinase Kd 5.96 CHEMBL
Serine/threonine-protein kinase 26 Kinase Kd 8.13 CHEMBL
Serine/threonine-protein kinase 32B Unclassified Kd 5.19 CHEMBL
Serine/threonine-protein kinase PAK 6 Kinase Kd 5.13 CHEMBL
Calcium/calmodulin-dependent protein kinase type 1D Kinase Kd 5.25 CHEMBL
Ribosomal protein S6 kinase alpha-2 Kinase Kd 5.39 CHEMBL
Mitogen-activated protein kinase kinase kinase 19 Kinase Kd 7.80 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 2 Kinase Kd 7.59 CHEMBL
Serine/threonine-protein kinase 33 Kinase Kd 6.03 CHEMBL
NUAK family SNF1-like kinase 2 Kinase Kd 6.85 CHEMBL
Mitogen-activated protein kinase kinase kinase 9 Kinase Kd 5.27 CHEMBL
Serine/threonine-protein kinase 35 Kinase Kd 5.35 CHEMBL
Mitogen-activated protein kinase kinase kinase MLT Kinase Kd 5.82 CHEMBL
Homeodomain-interacting protein kinase 4 Kinase Kd 5.82 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 5 Kinase Kd 7.20 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 7 Kinase Kd 6.28 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 4 Kinase Kd 6.48 CHEMBL
Tyrosine-protein kinase Fyn Kinase Kd 5.19 CHEMBL
Focal adhesion kinase 1 Kinase Kd 5.72 CHEMBL
Protein-tyrosine kinase 2-beta Kinase Kd 5.10 CHEMBL
Serine/threonine-protein kinase SIK1 Kinase Kd 6.66 CHEMBL
Wee1-like protein kinase 2 Kinase Kd 5.89 CHEMBL
Dual serine/threonine and tyrosine protein kinase Kinase Kd 5.19 CHEMBL
Tyrosine-protein kinase Mer Kinase Kd 6.40 CHEMBL
Tyrosine-protein kinase BTK Kinase Kd 6.80 CHEMBL
Insulin receptor Kinase Kd 5.52 CHEMBL
Tyrosine-protein kinase JAK3 Kinase Kd 5.70 CHEMBL
Hepatocyte growth factor receptor Kinase Kd 5.40 CHEMBL
Angiopoietin-1 receptor Kinase Kd 5.52 CHEMBL
Serine/threonine-protein kinase Chk2 Kinase Kd 6.07 CHEMBL
Activated CDC42 kinase 1 Kinase Kd 6.17 CHEMBL
Eukaryotic translation initiation factor 2-alpha kinase 4 Kinase Kd 7.02 CHEMBL
Misshapen-like kinase 1 Kinase Kd 7.54 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 1 Kinase Kd 7.03 CHEMBL
Serine/threonine-protein kinase Chk1 Kinase Kd 5.24 CHEMBL
Casein kinase I isoform gamma-2 Kinase Kd 5.18 CHEMBL
Interleukin-1 receptor-associated kinase 1 Kinase Kd 5.64 CHEMBL
Tyrosine-protein kinase receptor UFO Kinase Kd 6.72 CHEMBL
Tyrosine-protein kinase Blk Kinase Kd 7.07 CHEMBL
Cyclin-dependent kinase 7 Kinase Kd 5.29 CHEMBL
Casein kinase I isoform epsilon Kinase Kd 6.54 CHEMBL
Receptor tyrosine-protein kinase erbB-3 Kinase Kd 8.11 CHEMBL
Tyrosine-protein kinase Fes/Fps Kinase Kd 6.23 CHEMBL
Tyrosine-protein kinase HCK Kinase Kd 6.31 CHEMBL
Tyrosine-protein kinase Lyn Kinase Kd 6.09 CHEMBL
Mitogen-activated protein kinase kinase kinase 3 Kinase Kd 6.89 CHEMBL
Mitogen-activated protein kinase kinase kinase 11 Kinase Kd 5.24 CHEMBL
Mitogen-activated protein kinase kinase kinase 10 Kinase Kd 5.34 CHEMBL
Macrophage-stimulating protein receptor Kinase Kd 5.08 CHEMBL
Serine/threonine-protein kinase Nek2 Kinase Kd 6.60 CHEMBL
Serine/threonine-protein kinase Nek3 Kinase Kd 5.62 CHEMBL
Serine/threonine-protein kinase PAK 1 Kinase Kd 6.68 CHEMBL
Serine/threonine-protein kinase PAK 2 Kinase Kd 7.10 CHEMBL
Serine/threonine-protein kinase D1 Kinase Kd 6.09 CHEMBL
Mitogen-activated protein kinase 8 Kinase Kd 5.48 CHEMBL
Mitogen-activated protein kinase 10 Kinase Kd 5.60 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 1 Kinase Kd 7.85 CHEMBL
Ribosomal protein S6 kinase alpha-1 Kinase Kd 5.13 CHEMBL
Tyrosine-protein kinase SYK Kinase Kd 5.29 CHEMBL
Tyrosine-protein kinase TXK Kinase Kd 5.32 CHEMBL
Wee1-like protein kinase Kinase Kd 5.39 CHEMBL
Serine/threonine-protein kinase 24 Kinase Kd 8.19 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 3 Kinase Kd 8.11 CHEMBL
Receptor-type tyrosine-protein kinase FLT3 Kinase Kd 5.51 CHEMBL
Serine/threonine-protein kinase 17B Kinase Kd 5.96 CHEMBL
Tyrosine-protein kinase CSK Kinase Kd 6.26 CHEMBL
Casein kinase I isoform gamma-3 Kinase Kd 5.11 CHEMBL
Ephrin type-B receptor 6 Kinase Kd 5.55 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 2 Kinase Kd 6.66 CHEMBL
Mitogen-activated protein kinase kinase kinase 13 Kinase Kd 6.13 CHEMBL
Serine/threonine-protein kinase 17A Kinase Kd 6.47 CHEMBL

External reference:

IDSource
763563007 SNOMEDCT_US
017280 NDDF
1940643 RXNORM
d08621 MMSL
4036844 VANDF
736632003 SNOMEDCT_US
9RM7XY23ZS UNII
915942-22-2 SECONDARY_CAS_RN
9915743 PUBCHEM_CID
CHEBI:61397 CHEBI
CHEMBL180022 ChEMBL_ID
D08950 KEGG_DRUG
8878 INN_ID
DB11828 DRUGBANK_ID
CHEMBL3989921 ChEMBL_ID
5686 IUPHAR_LIGAND_ID
C487932 MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Nerlynx HUMAN PRESCRIPTION DRUG LABEL 1 70437-240 TABLET 40 mg ORAL NDA 18 sections