ceritinib 🐶 Veterinary Use | 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:

DoseUnitRoute
0.45 g O

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
March 28, 2016 PMDA NOVARTIS PHARMA K.K.
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 434.66 31.82 153 2417 67971 50534583
Metastases to central nervous system 248.69 31.82 66 2504 11216 50591338
Diarrhoea 128.10 31.82 152 2418 588324 50014230
Nausea 93.07 31.82 143 2427 705255 49897299
Vomiting 78.89 31.82 106 2464 460652 50141902
Death 66.73 31.82 82 2488 325297 50277257
Neoplasm progression 47.25 31.82 25 2545 29132 50573422
Non-small cell lung cancer 45.26 31.82 13 2557 2924 50599630
Alanine aminotransferase increased 43.64 31.82 36 2534 88323 50514231
Pericardial effusion 41.62 31.82 22 2548 25567 50576987
Aspartate aminotransferase increased 38.97 31.82 32 2538 77966 50524588
Decreased appetite 36.81 31.82 48 2522 200875 50401679
Hepatic function abnormal 36.60 31.82 22 2548 32659 50569895
Metastases to meninges 36.01 31.82 10 2560 1992 50600562
Metastases to liver 34.73 31.82 18 2552 20086 50582468
Hyperglycaemia 34.41 31.82 22 2548 36383 50566171

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 341.95 39.25 136 1602 73723 29499066
Metastases to central nervous system 147.81 39.25 41 1697 7090 29565699
Diarrhoea 79.68 39.25 97 1641 332601 29240188
Nausea 52.80 39.25 74 1664 289181 29283608
Pericarditis 46.59 39.25 18 1720 8739 29564050
Metastases to liver 44.60 39.25 19 1719 11837 29560952

FDA Adverse Event Reporting System (Geriatric)

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 634.74 30.77 241 3615 112630 64382246
Metastases to central nervous system 333.44 30.77 90 3766 13822 64481054
Diarrhoea 145.14 30.77 195 3661 722509 63772367
Nausea 111.12 30.77 180 3676 785620 63709256
Vomiting 89.72 30.77 135 3721 550982 63943894
Metastases to liver 75.27 30.77 34 3822 23907 64470969
Death 71.04 30.77 113 3743 482592 64012284
Pericardial effusion 59.37 30.77 34 3822 39220 64455656
Neoplasm progression 55.40 30.77 33 3823 40931 64453945
Non-small cell lung cancer 52.40 30.77 17 3839 4873 64490003
Alanine aminotransferase increased 51.91 30.77 52 3804 138979 64355897
Pericarditis 51.70 30.77 37 3819 62479 64432397
Decreased appetite 51.40 30.77 73 3783 281216 64213660
Hepatic function abnormal 48.50 30.77 36 3820 64277 64430599
Aspartate aminotransferase increased 46.92 30.77 46 3810 119742 64375134
Blood alkaline phosphatase increased 45.83 30.77 33 3823 56246 64438630
Metastases to meninges 43.70 30.77 13 3843 2802 64492074
Hyperglycaemia 41.27 30.77 32 3824 60936 64433940
Abdominal pain 37.57 30.77 67 3789 312308 64182568
Gastrointestinal toxicity 31.90 30.77 12 3844 5310 64489566
Gamma-glutamyltransferase increased 31.82 30.77 25 3831 48485 64446391
Transaminases increased 31.46 30.77 24 3832 44570 64450306

FDA Adverse Event Reporting System (Pediatric)

None

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
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000185504 Cytochrome P450 2C9 Inhibitors
FDA MoA N0000190114 Cytochrome P450 3A Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agents
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
ALK fusion gene-positive non-small-cell lung cancer indication 830151004




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

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, 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
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
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 5.90 CHEMBL
Multidrug resistance protein 1 Transporter EC50 7.05 CHEMBL
Tyrosine-protein kinase ABL1 Kinase IC50 5.90 CHEMBL
Mast/stem cell growth factor receptor Kit Kinase IC50 5.89 CHEMBL
Epidermal growth factor receptor Kinase IC50 6.05 CHEMBL
Proto-oncogene tyrosine-protein kinase Src Kinase IC50 5.77 CHEMBL
Tyrosine-protein kinase Lck Kinase IC50 6.25 CHEMBL
Receptor-type tyrosine-protein kinase FLT3 Kinase IC50 7.22 CHEMBL
Proto-oncogene tyrosine-protein kinase receptor Ret Kinase IC50 6.40 CHEMBL
Vascular endothelial growth factor receptor 2 Kinase IC50 5.38 CHEMBL
Platelet-derived growth factor receptor alpha Kinase IC50 5.94 CHEMBL
Cyclin-dependent kinase 2 Kinase IC50 5.40 CHEMBL
Fibroblast growth factor receptor 3 Kinase IC50 6.37 CHEMBL
Focal adhesion kinase 1 Kinase Kd 6.66 CHEMBL
Tyrosine-protein kinase JAK1 Kinase IC50 5.43 CHEMBL
High affinity nerve growth factor receptor Kinase IC50 5.56 CHEMBL
Tyrosine-protein kinase JAK2 Kinase IC50 6.21 CHEMBL
Rho-associated protein kinase 2 Kinase IC50 5.90 CHEMBL
Tyrosine-protein kinase SYK Kinase IC50 5.52 CHEMBL
Hepatocyte growth factor receptor Kinase IC50 5.87 CHEMBL
Tyrosine-protein kinase Lyn Kinase IC50 6.08 CHEMBL
Tyrosine-protein kinase Fer Kinase Kd 6.67 CHEMBL
Serine/threonine-protein kinase PLK4 Kinase Kd 5.15 CHEMBL
Fibroblast growth factor receptor 2 Kinase IC50 6.59 CHEMBL
Tyrosine-protein kinase Fgr Kinase IC50 5.71 CHEMBL
Dual specificity protein kinase CLK1 Kinase Kd 5.97 CHEMBL
Activated CDC42 kinase 1 Kinase Kd 6.03 CHEMBL
MAP kinase-interacting serine/threonine-protein kinase 2 Kinase IC50 5.65 CHEMBL
Calcium/calmodulin-dependent protein kinase kinase 2 Kinase Kd 5.26 CHEMBL
Tyrosine-protein kinase ZAP-70 Kinase IC50 5.01 CHEMBL
Tyrosine-protein kinase BTK Kinase IC50 5.47 CHEMBL
BDNF/NT-3 growth factors receptor Kinase IC50 5.74 CHEMBL
Non-receptor tyrosine-protein kinase TNK1 Kinase Kd 7.57 CHEMBL
Protein-tyrosine kinase 2-beta Kinase Kd 4.74 CHEMBL
Calcium/calmodulin-dependent protein kinase type IV Kinase Kd 6.20 CHEMBL
Mitogen-activated protein kinase 7 Kinase Kd 5.01 CHEMBL
Tyrosine-protein kinase Fes/Fps Kinase Kd 5.76 CHEMBL
Fibroblast growth factor receptor 4 Kinase IC50 6.02 CHEMBL
Proto-oncogene tyrosine-protein kinase ROS Kinase IC50 6.85 CHEMBL
Ribosomal protein S6 kinase alpha-1 Kinase Kd 4.67 CHEMBL
Tyrosine-protein kinase JAK3 Kinase IC50 5.10 CHEMBL
Transcription factor ETV6 Transcription factor IC50 5.49 CHEMBL
Insulin-like growth factor 1 receptor Kinase IC50 8.10 SCIENTIFIC LITERATURE
Insulin receptor Kinase AGONIST IC50 8.16 SCIENTIFIC LITERATURE
Testis-specific serine/threonine-protein kinase 1 Kinase IC50 7.64 SCIENTIFIC LITERATURE
Cyclin-dependent kinase 4 Kinase IC50 5.33 CHEMBL

External reference:

IDSource
K418KG2GET UNII
D10551 KEGG_DRUG
4033301 VUID
N0000190753 NUI
4033301 VANDF
C3818721 UMLSCUI
CHEBI:78432 CHEBI
4MK PDB_CHEM_ID
CHEMBL2403108 ChEMBL_ID
57379345 PUBCHEM_CID
DB09063 DRUGBANK_ID
9817 INN_ID
C586847 MESH_SUPPLEMENTAL_RECORD_UI
7397 IUPHAR_LIGAND_ID
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 0078-0694 TABLET, FILM COATED 150 mg ORAL NDA 30 sections
ZYKADIA HUMAN PRESCRIPTION DRUG LABEL 1 0078-0694 TABLET, FILM COATED 150 mg ORAL NDA 30 sections