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 441.40 34.72 156 2571 73431 56215909
Non-small cell lung cancer stage IV 272.40 34.72 38 2689 186 56289154
Metastases to central nervous system 251.71 34.72 67 2660 12069 56277271
Non-small cell lung cancer 238.43 34.72 51 2676 3607 56285733
Diarrhoea 123.69 34.72 152 2575 638355 55650985
Nausea 90.78 34.72 144 2583 764034 55525306
Vomiting 76.24 34.72 106 2621 498122 55791218
Death 66.61 34.72 82 2645 341344 55947996
Lung adenocarcinoma 48.49 34.72 15 2712 4559 56284781
Neoplasm progression 46.15 34.72 25 2702 31991 56257349
Alanine aminotransferase increased 43.28 34.72 36 2691 93626 56195714
Pericardial effusion 41.35 34.72 22 2705 27153 56262187
Aspartate aminotransferase increased 38.68 34.72 32 2695 82570 56206770
Lung neoplasm malignant 38.00 34.72 18 2709 17378 56271962
Hepatic function abnormal 36.42 34.72 22 2705 34536 56254804
Disease progression 35.79 34.72 34 2693 105139 56184201
Decreased appetite 35.28 34.72 48 2679 219183 56070157
Metastases to meninges 35.23 34.72 10 2717 2260 56287080

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 341.98 39.04 139 1739 78859 31616607
Non-small cell lung cancer 238.72 39.04 54 1824 4055 31691411
Metastases to central nervous system 149.21 39.04 42 1836 7594 31687872
Non-small cell lung cancer stage IV 141.63 39.04 22 1856 198 31695268
Diarrhoea 77.63 39.04 99 1779 352310 31343156
Nausea 53.06 39.04 77 1801 307870 31387596
Pericarditis 45.36 39.04 18 1860 9298 31686168
Metastases to liver 43.15 39.04 19 1859 12708 31682758
Lung neoplasm malignant 41.76 39.04 20 1858 16210 31679256

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 645.36 32.12 247 3865 121492 70802840
Non-small cell lung cancer stage IV 402.58 32.12 57 4055 255 70924077
Non-small cell lung cancer 384.32 32.12 86 4026 6261 70918071
Metastases to central nervous system 338.54 32.12 92 4020 14942 70909390
Diarrhoea 140.35 32.12 197 3915 783144 70141188
Nausea 109.62 32.12 184 3928 851904 70072428
Vomiting 88.07 32.12 137 3975 592974 70331358
Metastases to liver 73.73 32.12 34 4078 25844 70898488
Death 68.92 32.12 113 3999 509948 70414384
Lung adenocarcinoma 68.21 32.12 23 4089 7667 70916665
Pericardial effusion 58.37 32.12 34 4078 41742 70882590
Neoplasm progression 55.86 32.12 34 4078 45194 70879138
Lung neoplasm malignant 53.76 32.12 27 4085 24715 70899617
Alanine aminotransferase increased 52.48 32.12 53 4059 147427 70776905
Decreased appetite 48.61 32.12 73 4039 304707 70619625
Hepatic function abnormal 47.69 32.12 36 4076 67960 70856372
Aspartate aminotransferase increased 45.83 32.12 46 4066 126932 70797400
Blood alkaline phosphatase increased 45.57 32.12 33 4079 58488 70865844
Pericarditis 42.76 32.12 37 4075 84668 70839664
Metastases to meninges 42.71 32.12 13 4099 3123 70921209
Hyperglycaemia 40.46 32.12 32 4080 64640 70859692
Non-small cell lung cancer metastatic 36.71 32.12 9 4103 965 70923367
Transaminases increased 35.43 32.12 26 4086 46992 70877340
Abdominal pain 34.67 32.12 67 4045 342060 70582272
Non-small cell lung cancer stage IIIB 32.58 32.12 5 4107 42 70924290

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 | Suggest Off label Use Form| |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