ceritinib Indications/Contra | FAERs-F | FAERs-M | Orange Bk | 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

  • Status: ONP

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

Drug dosage:

None

ADMET properties:

None

Approvals:

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

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
Malignant neoplasm progression 618.27 56.80 129 493 11999 2345464
Diarrhoea 391.35 56.80 134 488 83430 2274033
Nausea 330.50 56.80 128 494 112061 2245402
Non-small cell lung cancer stage IV 302.55 56.80 36 586 48 2357415
Metastases to central nervous system 281.77 56.80 51 571 2097 2355366
Vomiting 249.07 56.80 93 529 71509 2285954
Non-small cell lung cancer 248.53 56.80 38 584 535 2356928
Decreased appetite 126.72 56.80 45 577 28846 2328617
Pericarditis 109.86 56.80 22 600 1518 2355945
Death 104.90 56.80 53 569 81415 2276048
Abdominal pain 101.11 56.80 40 582 34334 2323129
Alanine aminotransferase increased 93.44 56.80 30 592 14002 2343461
Dyspnoea 88.99 56.80 47 575 78686 2278777
General physical health deterioration 85.06 56.80 28 594 14111 2343352
Fatigue 80.12 56.80 45 577 84828 2272635
Aspartate aminotransferase increased 79.97 56.80 26 596 12586 2344877
Pericardial effusion 78.89 56.80 20 602 3989 2353474
Hyperglycaemia 70.24 56.80 19 603 4866 2352597
Chest pain 66.27 56.80 28 594 28109 2329354
Hepatic function abnormal 66.09 56.80 19 603 6073 2351390
Lung neoplasm malignant 63.90 56.80 16 606 3026 2354437
Metastases to liver 59.44 56.80 15 607 2926 2354537

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
Malignant neoplasm progression 465.66 54.29 110 377 14048 1732246
Non-small cell lung cancer 255.26 54.29 41 446 621 1745673
Diarrhoea 176.70 54.29 72 415 53780 1692514
Metastases to central nervous system 176.29 54.29 34 453 1511 1744783
Nausea 152.36 54.29 64 423 51132 1695162
Non-small cell lung cancer stage IV 136.48 54.29 18 469 55 1746239
Vomiting 90.50 54.29 41 446 38274 1708020
Pericarditis 76.17 54.29 17 470 1521 1744773
Lung neoplasm malignant 68.69 54.29 18 469 3161 1743133
Chest pain 55.31 54.29 24 463 19890 1726404

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