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 418.43 32.95 150 2419 64776 46618717
Non-small cell lung cancer stage IV 265.43 32.95 38 2531 199 46683294
Non-small cell lung cancer 228.31 32.95 49 2520 3095 46680398
Metastases to central nervous system 225.13 32.95 62 2507 11159 46672334
Diarrhoea 116.28 32.95 147 2422 559455 46124038
Nausea 80.44 32.95 138 2431 687316 45996177
Vomiting 72.23 32.95 105 2464 452689 46230804
Death 49.22 32.95 75 2494 335473 46348020
Lung adenocarcinoma 43.71 32.95 14 2555 4190 46679303
Pericarditis 41.35 32.95 22 2547 23905 46659588
Pericardial effusion 40.00 32.95 22 2547 25521 46657972
Alanine aminotransferase increased 39.09 32.95 35 2534 88416 46595077
Neoplasm progression 36.41 32.95 21 2548 26662 46656831
Decreased appetite 35.14 32.95 48 2521 193788 46489705
Lung neoplasm malignant 34.78 32.95 17 2552 15472 46668021
Aspartate aminotransferase increased 34.49 32.95 31 2538 78669 46604824
Hyperglycaemia 33.55 32.95 22 2547 35049 46648444

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 329.32 38.95 130 1555 72157 29878636
Non-small cell lung cancer 235.67 38.95 52 1633 3678 29947115
Metastases to central nervous system 148.74 38.95 41 1644 7243 29943550
Non-small cell lung cancer stage IV 121.58 38.95 19 1666 189 29950604
Diarrhoea 61.85 38.95 84 1601 334019 29616774
Nausea 49.33 38.95 71 1614 296886 29653907
Pericarditis 47.66 38.95 18 1667 8588 29942205
Lung neoplasm malignant 44.10 38.95 20 1665 15112 29935681
Metastases to liver 41.92 38.95 18 1667 11947 29938846

Pharmacologic Action:

SourceCodeDescription
ATC L01ED02 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Anaplastic lymphoma kinase (ALK) inhibitors
FDA MoA N0000020001 Tyrosine Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
FDA MoA N0000185504 Cytochrome P450 2C9 Inhibitors
FDA MoA N0000190114 Cytochrome P450 3A Inhibitors
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:62434 alk inhibitor

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)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
150MG ZYKADIA NOVARTIS N205755 April 29, 2014 DISCN CAPSULE ORAL April 29, 2021 TREATMENT OF PATIENTS WITH ANULLPLASTIC LYMPHOMA KINULLSE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHO HAVE PROGRESSED ON OR ARE INTOLERANT TO CRIZOTINIB.
150MG ZYKADIA NOVARTIS N211225 March 18, 2019 RX TABLET ORAL April 29, 2021 FDA HAS NOT RECOGNIZED ORPHAN-DRUG EXCLUSIVITY (ODE) FOR THIS DRUG, BUT IT CONTAINS THE SAME ACTIVE MOIETY OR MOIETIES AS ANOTHER DRUG(S) THAT WAS ELIGIBLE FOR ODE, AND ALSO SHARES ODE-PROTECTED USE(S) OR INDICATION(S) WITH THAT DRUG(S). AN APPLICATION SEEKING APPROVAL FOR THE SAME ACTIVE MOIETY OR MOIETIES, INCLUDING AN ANDA THAT CITES THIS NDA AS ITS BASIS OF SUBMISSION, MAY NOT BE APPROVED FOR SUCH ODE-PROTECTED USE(S) AND INDICATION(S)
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 ANULLPLASTIC LYMPHOMA KINULLSE (ALK)-POSITIVE AS DETECTED BY AN FDA-APPROVED TEST
150MG ZYKADIA NOVARTIS N211225 March 18, 2019 RX TABLET ORAL May 26, 2024 FDA HAS NOT RECOGNIZED ORPHAN-DRUG EXCLUSIVITY (ODE) FOR THIS DRUG, BUT IT CONTAINS THE SAME ACTIVE MOIETY OR MOIETIES AS ANOTHER DRUG(S) THAT WAS ELIGIBLE FOR ODE, AND ALSO SHARES ODE-PROTECTED USE(S) OR INDICATION(S) WITH THAT DRUG(S). AN APPLICATION SEEKING APPROVAL FOR THE SAME ACTIVE MOIETY OR MOIETIES, INCLUDING AN ANDA THAT CITES THIS NDA AS ITS BASIS OF SUBMISSION, MAY NOT BE APPROVED FOR SUCH ODE-PROTECTED USE(S) AND INDICATION(S)

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
Fibroblast growth factor receptor 2 Kinase IC50 6.59 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 JAK2 Kinase IC50 6.21 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
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
4033301 VANDF
C3818721 UMLSCUI
CHEBI:78432 CHEBI
4MK PDB_CHEM_ID
CHEMBL2403108 ChEMBL_ID
DB09063 DRUGBANK_ID
C586847 MESH_SUPPLEMENTAL_RECORD_UI
57379345 PUBCHEM_CID
7397 IUPHAR_LIGAND_ID
9817 INN_ID
K418KG2GET UNII
1535457 RXNORM
219616 MMSL
30281 MMSL
d08255 MMSL
015504 NDDF
703146007 SNOMEDCT_US
704310000 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
ZYKADIA HUMAN PRESCRIPTION DRUG LABEL 1 0078-0640 CAPSULE 150 mg ORAL NDA 28 sections
ZYKADIA HUMAN PRESCRIPTION DRUG LABEL 1 0078-0694 TABLET, FILM COATED 150 mg ORAL NDA 28 sections