ceritinib Indications/Contra | FAERs | Orange Book | BioActivity |

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 4866 1032900-25-6

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • NVP-LDK378-NX
  • ceritinib
  • zykadia
  • LDK378
Ceritinib is a kinase inhibitor. Targets of ceritinib inhibition identified in either biochemical or cellular assays at clinically relevant concentrations include ALK, insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (InsR), and ROS1. Among these, ceritinib is most active against ALK. Ceritinib inhibited autophosphorylation of ALK, ALK-mediated phosphorylation of the downstream signaling protein STAT3, and proliferation of ALK-dependent cancer cells in in vitro and in vivo assays.
  • Molecular weight: 558.14
  • Formula: C28H36ClN5O3S
  • CLOGP: 6.41
  • LIPINSKI: 2
  • HAC: 8
  • HDO: 3
  • TPSA: 105.24
  • ALOGS: -5.40
  • ROTB: 9

Drug dosage:

None

Approvals:

DateAgencyCompanyOrphan
Feb. 26, 2015 EMA
April 29, 2014 FDA NOVARTIS PHARMS CORP

FDA Adverse Event Reporting System

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
Malignant neoplasm progression 1165.24 54.43 262 1029 28774 4608927
Diarrhoea 578.96 54.43 220 1071 149965 4487736
Non-small cell lung cancer 546.19 54.43 87 1204 1343 4636358
Nausea 511.84 54.43 211 1080 177122 4460579
Metastases to central nervous system 498.22 54.43 94 1197 4030 4633671
Non-small cell lung cancer stage IV 431.13 54.43 54 1237 105 4637596
Vomiting 353.88 54.43 146 1145 119553 4518148
Pericarditis 196.63 54.43 42 1249 3313 4634388
Death 180.18 54.43 109 1182 198054 4439647
Decreased appetite 172.22 54.43 71 1220 56326 4581375
Abdominal pain 154.64 54.43 67 1224 59957 4577744
Lung neoplasm malignant 146.77 54.43 38 1253 6868 4630833
Dyspnoea 137.45 54.43 81 1210 138904 4498797
Pericardial effusion 131.41 54.43 36 1255 8062 4629639
Alanine aminotransferase increased 129.79 54.43 48 1243 28325 4609376
General physical health deterioration 125.46 54.43 47 1244 28731 4608970
Fatigue 118.57 54.43 75 1216 145491 4492210
Neoplasm 118.13 54.43 26 1265 2345 4635356
Chest pain 115.50 54.43 52 1239 50648 4587053
Disease progression 109.32 54.43 47 1244 40964 4596737
Metastases to liver 105.17 54.43 28 1263 5614 4632087
Hyperglycaemia 102.44 54.43 32 1259 11290 4626411
Aspartate aminotransferase increased 102.34 54.43 39 1252 24899 4612802
Lung adenocarcinoma 99.97 54.43 21 1270 1516 4636185
Hepatic function abnormal 98.77 54.43 33 1258 14403 4623298
Blood creatinine increased 92.45 54.43 37 1254 26863 4610838
Pneumonia 83.42 54.43 53 1238 102762 4534939
Blood alkaline phosphatase increased 79.23 54.43 27 1264 12480 4625221
Weight decreased 78.83 54.43 41 1250 54423 4583278
Gamma-glutamyltransferase increased 70.11 54.43 24 1267 11230 4626471
C-reactive protein increased 63.31 54.43 23 1268 12789 4624912
Transaminases increased 61.84 54.43 21 1270 9585 4628116
Pleural effusion 61.70 54.43 27 1264 24371 4613330
Gastrointestinal toxicity 60.60 54.43 14 1277 1563 4636138
Gastrointestinal disorder 58.25 54.43 23 1268 16038 4621663
Renal impairment 57.52 54.43 26 1265 25312 4612389
Non-small cell lung cancer metastatic 57.19 54.43 10 1281 269 4637432
Neoplasm progression 55.58 54.43 19 1272 8836 4628865
Pyrexia 55.53 54.43 42 1249 107102 4530599
Liver disorder 55.47 54.43 21 1270 13077 4624624
Pneumonitis 54.85 54.43 19 1272 9191 4628510

Pharmacologic Action:

SourceCodeDescription
ATC L01XE28 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 N0000020001 Tyrosine Kinase Inhibitors
FDA MoA N0000190114 Cytochrome P450 3A Inhibitors
FDA MoA N0000185504 Cytochrome P450 2C9 Inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Non-small cell lung cancer indication 254637007 DOID:3908

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 10.21 Basic
pKa2 2.49 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
150MG ZYKADIA NOVARTIS N205755 April 29, 2014 DISCN CAPSULE ORAL 8377921 Nov. 20, 2027 TREATMENT OF A CANCER MEDIATED BY AN ANAPLASTIC LYMPHOMA KINASE (ALK)
150MG ZYKADIA NOVARTIS N211225 March 18, 2019 RX TABLET ORAL 8377921 Nov. 20, 2027 TREATMENT OF A CANCER MEDIATED BY AN ANAPLASTIC LYMPHOMA KINASE (ALK)
150MG ZYKADIA NOVARTIS N205755 April 29, 2014 DISCN CAPSULE ORAL 8703787 Feb. 2, 2032 TREATMENT OF A CANCER MEDIATED BY AN ANAPLASTIC LYMPHOMA KINASE (ALK)
150MG ZYKADIA NOVARTIS N211225 March 18, 2019 RX TABLET ORAL 8703787 Feb. 2, 2032 TREATMENT OF A CANCER MEDIATED BY AN ANAPLASTIC LYMPHOMA KINASE (ALK)

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
150MG ZYKADIA NOVARTIS N205755 April 29, 2014 DISCN CAPSULE ORAL May 26, 2020 INFORMATION ADDED TO LABELING REGARDING THE TREATMENT OF PATIENTS WITH ALK-POSITIVE NON-SMALL CELL LUNG CANCER (NSCLC) WHO HAD NOT RECEIVED PRIOR SYSTEMIC THERAPY FOR METASTATIC DISEASE.
150MG ZYKADIA NOVARTIS N205755 April 29, 2014 DISCN CAPSULE ORAL April 29, 2021 TREATMENT OF PATIENTS WITH ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHO HAVE PROGRESSED ON OR ARE INTOLERANT TO CRIZOTINIB.
150MG ZYKADIA NOVARTIS N205755 April 29, 2014 DISCN CAPSULE ORAL May 26, 2024 TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS ARE ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE AS DETECTED BY AN FDA-APPROVED TEST

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
ALK tyrosine kinase receptor Kinase INHIBITOR IC50 9.70 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Insulin receptor Kinase AGONIST IC50 8.15 SCIENTIFIC LITERATURE
Testis-specific serine/threonine-protein kinase 1 Kinase IC50 7.64 SCIENTIFIC LITERATURE
Tyrosine-protein kinase JAK2 Kinase IC50 6.21 CHEMBL
Tyrosine-protein kinase ABL1 Kinase IC50 5.90 CHEMBL
Receptor-type tyrosine-protein kinase FLT3 Kinase IC50 7.22 CHEMBL
Epidermal growth factor receptor Kinase IC50 6.05 CHEMBL
Proto-oncogene tyrosine-protein kinase Src Kinase IC50 5.77 CHEMBL
Vascular endothelial growth factor receptor 2 Kinase IC50 5.38 CHEMBL
Fibroblast growth factor receptor 3 Kinase IC50 6.37 CHEMBL
Fibroblast growth factor receptor 4 Kinase IC50 6.02 CHEMBL
Platelet-derived growth factor receptor alpha Kinase IC50 5.94 CHEMBL
Hepatocyte growth factor receptor Kinase IC50 5.87 CHEMBL
Tyrosine-protein kinase JAK1 Kinase IC50 5.43 CHEMBL
Tyrosine-protein kinase SYK Kinase IC50 5.52 CHEMBL
Tyrosine-protein kinase BTK Kinase IC50 5.47 CHEMBL
Tyrosine-protein kinase Fgr Kinase IC50 5.71 CHEMBL
Tyrosine-protein kinase JAK3 Kinase IC50 5.10 CHEMBL
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 5.90 CHEMBL
High affinity nerve growth factor receptor Kinase IC50 5.56 CHEMBL
Fibroblast growth factor receptor 2 Kinase IC50 6.59 CHEMBL
Mast/stem cell growth factor receptor Kit Kinase IC50 5.89 CHEMBL
MAP kinase-interacting serine/threonine-protein kinase 2 Kinase IC50 5.65 CHEMBL
Tyrosine-protein kinase Lyn Kinase IC50 6.08 CHEMBL
Tyrosine-protein kinase ZAP-70 Kinase IC50 5.01 CHEMBL
Cyclin-dependent kinase 2 Kinase IC50 5.40 CHEMBL
Proto-oncogene tyrosine-protein kinase ROS Kinase IC50 6.85 CHEMBL
Rho-associated protein kinase 2 Kinase IC50 5.90 CHEMBL
Transcription factor ETV6 Transcription factor IC50 5.49 CHEMBL
Proto-oncogene tyrosine-protein kinase receptor Ret Kinase IC50 6.40 CHEMBL
Tyrosine-protein kinase Lck Kinase IC50 6.25 CHEMBL
BDNF/NT-3 growth factors receptor Kinase IC50 5.74 CHEMBL
Insulin-like growth factor 1 receptor Kinase IC50 8.10 SCIENTIFIC LITERATURE
Cyclin-dependent kinase 4 Kinase IC50 5.33 CHEMBL

External reference:

IDSource
D10551 KEGG_DRUG
4033301 VUID
N0000190753 NUI
C3818721 UMLSCUI
704310000 SNOMEDCT_US
015504 NDDF
30281 MMSL
d08255 MMSL
4033301 VANDF
703146007 SNOMEDCT_US
1535457 RXNORM
57379345 PUBCHEM_CID
CHEBI:78432 CHEBI
K418KG2GET UNII
9817 INN_ID
4MK PDB_CHEM_ID
DB09063 DRUGBANK_ID
7397 IUPHAR_LIGAND_ID
CHEMBL2403108 ChEMBL_ID
C586847 MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
ZYKADIA HUMAN PRESCRIPTION DRUG LABEL 1 0078-0640 CAPSULE 150 mg ORAL NDA 16 sections
ZYKADIA HUMAN PRESCRIPTION DRUG LABEL 1 0078-0694 TABLET, FILM COATED 150 mg ORAL NDA 16 sections