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 453.07 35.92 158 2529 81963 63404372
Metastases to central nervous system 265.26 35.92 69 2618 13036 63473299
Diarrhoea 129.70 35.92 154 2533 715212 62771123
Nausea 99.11 35.92 148 2539 854323 62632012
Vomiting 84.02 35.92 110 2577 559507 62926828
Death 69.47 35.92 82 2605 374299 63112036
Neoplasm progression 49.11 35.92 26 2661 36402 63449933
Non-small cell lung cancer 45.01 35.92 13 2674 3582 63482753
Alanine aminotransferase increased 44.32 35.92 36 2651 103734 63382601
Pericardial effusion 42.06 35.92 22 2665 30036 63456299
Hepatic function abnormal 40.37 35.92 23 2664 37119 63449216
Aspartate aminotransferase increased 39.98 35.92 32 2655 90245 63396090
Disease progression 39.06 35.92 36 2651 122722 63363613
Decreased appetite 38.36 35.92 50 2637 251002 63235333

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 344.94 36.14 139 1681 87907 34867204
Metastases to central nervous system 156.23 36.14 43 1777 8162 34946949
Diarrhoea 83.19 36.14 101 1719 389811 34565300
Nausea 56.42 36.14 78 1742 339830 34615281
Metastases to liver 44.22 36.14 19 1801 13644 34941467
Pericarditis 43.72 36.14 18 1802 11627 34943484
Vomiting 41.16 36.14 57 1763 247564 34707547

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 651.60 30.90 247 3788 135743 79604610
Metastases to central nervous system 357.42 30.90 95 3940 16280 79724073
Diarrhoea 147.95 30.90 200 3835 880289 78860064
Nausea 117.88 30.90 188 3847 957008 78783345
Vomiting 97.45 30.90 142 3893 665686 79074667
Metastases to liver 75.24 30.90 34 4001 28280 79712073
Death 72.96 30.90 114 3921 566400 79173953
Pericardial effusion 59.46 30.90 34 4001 46203 79694150
Neoplasm progression 58.54 30.90 35 4000 51647 79688706
Decreased appetite 57.14 30.90 78 3957 342340 79398013
Alanine aminotransferase increased 54.22 30.90 53 3982 162517 79577836
Hepatic function abnormal 52.04 30.90 37 3998 73070 79667283
Non-small cell lung cancer 50.80 30.90 17 4018 6343 79734010
Blood alkaline phosphatase increased 49.46 30.90 34 4001 63630 79676723
Aspartate aminotransferase increased 47.71 30.90 46 3989 138595 79601758
Metastases to meninges 42.68 30.90 13 4022 3588 79736765
Hyperglycaemia 41.94 30.90 32 4003 70303 79670050
Pericarditis 40.48 30.90 37 3998 104199 79636154
Transaminases increased 38.69 30.90 27 4008 51716 79688637
Abdominal pain 36.21 30.90 68 3967 389501 79350852
Gamma-glutamyltransferase increased 32.86 30.90 25 4010 54655 79685698
Metastases to bone 31.48 30.90 18 4017 24409 79715944

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
ZYKADIA HUMAN PRESCRIPTION DRUG LABEL 1 0078-0694 TABLET, FILM COATED 150 mg ORAL NDA 30 sections