ceritinib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | 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

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
kinase-safety-class AAK1,ABL1,ABL2,ACVR2A,ACVR2B,AKT3,ALK,AURKA,AURKB,AURKC,AXL,BLK,BMX,BRAF,BTK,CAMK1,CAMK2A,CAMK2B,CAMK2D,CAMK2G,CDK1,CDK14,CDK16,CDK19,CDK2,CDK3,CDK4,CDK7,CDK9,CHEK1,CHEK2,CLK1,CLK2,CLK4,CSF1R,CSK,CSNK2A2,DDR1,DYRK1A,DYRK1B,EGFR,EIF2AK3,EPHA2,EPHB1,EPHB4,ERBB2,ERBB4,FGFR1,FGFR4,FLT1,FLT3,FLT4,FYN,GAK,GRK1,GRK2,GSK3A,GSK3B,HASPIN,HIPK2,IGF1R,INSR,INSRR,IRAK1,IRAK3,IRAK4,ITK,JAK1,JAK2,JAK3,KDR,KIT,LCK,LRRK2,LYN,MAP2K1,MAP2K4,MAP2K6,MAP3K1,MAP3K10,MAP3K11,MAP3K14,MAP3K19,MAP3K21,MAP3K7,MAP3K9,MAP4K1,MAP4K2,MAP4K3,MAP4K5,MAPK1,MAPK10,MAPK15,MAPK3,MAPK7,MAPK9,MARK1,MARK2,MARK3,MARK4,MELK,MET,MINK1,MKNK1,MKNK2,MST1R,MYLK,NTRK1,NTRK2,NUAK1,PAK1,PAK2,PAK4,PAK5,PDGFRB,PDK1,PDK2,PDK4,PDPK1,PIK3CA,PIM1,PIM3,PLK1,PLK2,PLK3,PLK4,PRKAA1,PRKAA2,PRKACA,PRKCA,PRKCD,PRKCI,PRKCQ,PRKCZ,PRKD1,PRKDC,PTK2,PTK6,RET,RIPK3,ROCK1,ROCK2,RPS6KA1,SIK2,SIK3,SRC,SRPK1,STK10,STK16,STK17A,STK3,STK33,STK4,SYK,TBK1,TEK,TNIK,TNK1,TTK,UHMK1,ULK1,ULK2,YES1,ZAP70 164
kinase-selectivity-class AAK1,ABL2,ACVR2B,ALK,AURKA,AXL,BLK,BTK,CAMK2A,CAMK2B,CAMK2D,CDK1,CDK7,CDK9,CHEK1,CLK2,CLK4,CSF1R,DDR1,DYRK1A,DYRK1B,DYRK2,EGFR,EIF2AK3,EPHB4,ERBB2,ERBB4,FGFR1,FGFR4,FLT1,FLT3,FYN,GAK,IGF1R,INSR,IRAK1,IRAK3,IRAK4,JAK1,JAK2,JAK3,KDR,KIT,LCK,LRRK2,LYN,MAP3K10,MAP3K11,MAP3K14,MAP3K21,MAP3K7,MAP3K9,MAP4K1,MAP4K3,MAPK7,MARK1,MARK2,MARK4,MELK,MET,MINK1,MKNK1,MKNK2,NTRK1,NUAK1,PAK4,PDGFRB,PDK1,PDK4,PIM3,PLK1,PLK4,PRKAA1,PRKAA2,PRKCD,PTK2,RET,RIPK3,SIK2,SIK3,SRC,STK10,STK33,STK4,SYK,TNIK,TNK1,TTK,ULK1,ULK2,YES1 91
pfas-class PFAS structural alert (1 = True, 0 = False) 0

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 472.57 33.48 161 2640 106709 90518937
Metastases to central nervous system 281.46 33.48 72 2729 17470 90608176
Diarrhoea 141.79 33.48 158 2643 939032 89686614
Nausea 112.61 33.48 153 2648 1110163 89515483
Vomiting 81.51 33.48 110 2691 788183 89837463
Death 80.84 33.48 84 2717 456467 90169179
Neoplasm progression 54.88 33.48 27 2774 44459 90581187
Disease progression 49.54 33.48 40 2761 156575 90469071
Alanine aminotransferase increased 47.88 33.48 35 2766 118303 90507343
Non-small cell lung cancer 46.50 33.48 13 2788 4368 90621278
Pericardial effusion 44.37 33.48 22 2779 36811 90588835
Aspartate aminotransferase increased 42.90 33.48 31 2770 102906 90522740
Decreased appetite 42.40 33.48 55 2746 376485 90249161
Hepatic function abnormal 42.39 33.48 23 2778 46265 90579381
Hyperglycaemia 37.66 33.48 22 2779 50948 90574698
Metastases to liver 37.06 33.48 18 2783 28789 90596857
Blood alkaline phosphatase increased 36.17 33.48 21 2780 48058 90577588
Metastases to meninges 34.75 33.48 10 2791 3725 90621921

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 357.72 35.69 146 1808 108254 42511127
Metastases to central nervous system 174.64 35.69 48 1906 10307 42609074
Diarrhoea 84.69 35.69 104 1850 460745 42158636
Nausea 60.73 35.69 82 1872 396717 42222664
Metastases to liver 49.87 35.69 21 1933 16305 42603076
Pericarditis 43.43 35.69 18 1936 13426 42605955
Vomiting 41.29 35.69 58 1896 289665 42329716

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 687.74 31.96 255 3979 174312 110410753
Metastases to central nervous system 376.08 31.96 100 4134 22717 110562348
Diarrhoea 162.16 31.96 207 4027 1139298 109445767
Nausea 132.58 31.96 196 4038 1235494 109349571
Vomiting 95.09 31.96 143 4091 910532 109674533
Metastases to liver 83.57 31.96 36 4198 35350 110549715
Death 83.35 31.96 117 4117 698752 109886313
Decreased appetite 64.67 31.96 85 4149 475761 110109304
Neoplasm progression 63.02 31.96 36 4198 64559 110520506
Pericardial effusion 61.55 31.96 34 4200 57183 110527882
Alanine aminotransferase increased 61.31 31.96 53 4181 183720 110401345
Blood alkaline phosphatase increased 59.89 31.96 36 4198 70899 110514166
Hepatic function abnormal 59.51 31.96 39 4195 89256 110495809
Non-small cell lung cancer 55.81 31.96 18 4216 7917 110577148
Aspartate aminotransferase increased 53.07 31.96 46 4188 159890 110425175
Metastases to meninges 45.96 31.96 14 4220 5114 110579951
Hyperglycaemia 44.47 31.96 32 4202 85058 110500007
Transaminases increased 42.98 31.96 28 4206 63362 110521703
Abdominal pain 37.63 31.96 69 4165 512920 110072145
Gamma-glutamyltransferase increased 36.55 31.96 25 4209 61284 110523781
Blood creatinine increased 33.39 31.96 38 4196 182851 110402214
Pleural effusion 32.57 31.96 37 4197 177672 110407393
Non-small cell lung cancer metastatic 32.38 31.96 8 4226 1344 110583721
Metastases to bone 31.96 31.96 18 4216 31354 110553711

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 D000092004 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 agent
CHEBI has role CHEBI:62434 EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor

Related Drugs by ATC class:

L01ED Anaplastic lymphoma kinase (ALK) inhibitors 4 drugs
alectinibbrigatinibcrizotiniblorlatinib

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)
150MG ZYKADIA NOVARTIS N211225 March 18, 2019 RX TABLET ORAL 12357630 Dec. 13, 2037 TREATMENT OF ADULT PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS ARE ANAPLASTIC LYMPHOMA KINASE (ALK)-POSITIVE AS DETECTED BY AN FDA-APPROVED TEST

Orange Book exclusivity data (new drug applications)

None

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
K418KG2GET INXIGHT DRUGS

Pharmaceutical products:

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