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

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 5424 1100598-32-0

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • tepotinib
  • tepotinib hydrochloride
  • tepmetko
  • EMD-1214063
  • MSC-2156119
  • MSC-2156119J
Tepotinib is a MET (mesenchymal-epithelial transition factor) tyrosine kinase inhibitor being developed for the treatment of solid tumours. It selectively binds to MET and inhibits MET phosphorylation disrupting the oncogenic MET receptor signalling caused by MET gene alterations, including both MET exon 14 (METex14) skipping alterations and MET protein overexpression. This results in cell death in tumour cells overexpressing MET protein or expressing constitutively activated MET protein.
  • Molecular weight: 492.58
  • Formula: C29H28N6O2
  • CLOGP: 3.40
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 0
  • TPSA: 94.71
  • ALOGS: -4.69
  • ROTB: 7

  • 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
azlogd74 LogD at pH 7.4 2.413 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 4.487 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 7.516 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 20.606 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 5.520 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 16.250 % High 1
herg hERG pIC50 5.870 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 4.853 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 46.881 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 3.750 % High 1
kinase-safety-class ACVR2B,AXL,CAMK2D,EIF2AK3,GRK2,ITK,MET,PDK1,PDK2,PDK4,PRKDC 11
kinase-selectivity-class CAMK2D,EIF2AK3,MET 3
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 12.417 High 1
mh-clint Mouse hepatocyte intrinsic clearance 29.923 High 1
mppb Mouse plasma protein binding (% unbound) 3.910 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 52 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 9.150 % High 1
rat-kpuu-brain Rat brain Kpuu 0.019 % High 1
rh-clint Rat hepatocyte intrinsic clearance 26.002 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 19.970 % High 1
rppb Rat plasma protein binding (% unbound) 3.630 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 61.660 uM High 1

Approvals:

DateAgencyCompanyOrphan
March 25, 2020 PMDA Merck KGaA
Feb. 3, 2021 FDA EMD SERONO INC
Feb. 16, 2022 EMA Merck Europe B.V.

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
Oedema peripheral 106.49 69.08 39 317 257876 90370215
Death 78.60 69.08 37 319 456514 90171577

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
Oedema peripheral 102.69 68.75 39 312 136037 42484947
Renal impairment 73.52 68.75 29 322 110199 42510785

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
Oedema peripheral 146.88 63.19 59 595 328601 110260044
Renal impairment 124.05 63.19 45 609 188400 110400245
Oedema 73.95 63.19 32 622 209944 110378701
Disease progression 72.50 63.19 33 621 244001 110344644

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EP02 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Cellular-mesenchymal-epithelial transition factor (c-MET) kinase inhibitors
MeSH PA D000970 Antineoplastic Agents
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000185503 P-Glycoprotein Inhibitors
FDA MoA N0000193929 Mesenchymal Epithelial Transition Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent

Related Drugs by ATC class:

L01EP Cellular-mesenchymal-epithelial transition factor (c-MET) kinase inhibitors 1 drug

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Non-small cell lung cancer indication 254637007 DOID:3908
Metastatic non-small cell lung cancer indication




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 225MG BASE TEPMETKO EMD SERONO INC N214096 Feb. 3, 2021 RX TABLET ORAL 8658643 July 4, 2028 TREATING A SOLID TUMOR, INCLUDING LUNG CANCER, WITH A MET ALTERATION(S), OR STABILIZING OR IMPROVING SYMPTOMS ASSOCIATED WITH HAVING A SOLID TUMOR, INCLUDING LUNG CANCER, WITH A MET ALTERATION(S), BY ADMINISTERING AN EFFECTIVE AMOUNT OF TEPOTINIB
EQ 225MG BASE TEPMETKO EMD SERONO INC N214096 Feb. 3, 2021 RX TABLET ORAL 9403799 July 4, 2028 TREATING A SOLID TUMOR, INCLUDING LUNG CANCER, WITH A MET ALTERATION(S), OR STABILIZING OR IMPROVING SYMPTOMS ASSOCIATED WITH HAVING A SOLID TUMOR, INCLUDING LUNG CANCER, WITH A MET ALTERATION(S), BY ADMINISTERING AN EFFECTIVE AMOUNT OF TEPOTINIB
EQ 225MG BASE TEPMETKO EMD SERONO INC N214096 Feb. 3, 2021 RX TABLET ORAL 8927540 July 21, 2028 TREATING A SOLID TUMOR, INCLUDING LUNG CANCER, HAVING A MET KINASE ALTERATION(S) BY ADMINISTERING AN EFFECTIVE AMOUNT OF TEPOTINIB

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 225MG BASE TEPMETKO EMD SERONO INC N214096 Feb. 3, 2021 RX TABLET ORAL Feb. 3, 2026 NEW CHEMICAL ENTITY
EQ 225MG BASE TEPMETKO EMD SERONO INC N214096 Feb. 3, 2021 RX TABLET ORAL Feb. 3, 2028 TREATMENT OF ADULT PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) HARBORING MESENCHYMAL-EPITHELIAL TRANSITION (MET) EXON 14 SKIPPING ALTERATIONS

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Hepatocyte growth factor receptor Kinase INHIBITOR IC50 8.77 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Ribosyldihydronicotinamide dehydrogenase [quinone] Enzyme Kd 6.06 CHEMBL
Interleukin-1 receptor-associated kinase 4 Kinase INHIBITOR IC50 6.21 SCIENTIFIC LITERATURE

External reference:

IDSource
D11073 KEGG_DRUG
1IJV77EI07 UNII
1946826-82-9 SECONDARY_CAS_RN
C4287799 UMLSCUI
CHEBI:755350 CHEBI
3E8 PDB_CHEM_ID
CHEMBL3402762 ChEMBL_ID
25171648 PUBCHEM_CID
DB15133 DRUGBANK_ID
CHEMBL4594292 ChEMBL_ID
9934 INN_ID
C000707607 MESH_SUPPLEMENTAL_RECORD_UI
C582858 MESH_SUPPLEMENTAL_RECORD_UI
8293 IUPHAR_LIGAND_ID
1148537007 SNOMEDCT_US
1148545002 SNOMEDCT_US
1148549008 SNOMEDCT_US
4040036 VANDF
4040037 VANDF
343294 MMSL
39305 MMSL
d09709 MMSL
018627 NDDF
018628 NDDF
2477103 RXNORM
1IJV77EI07 INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
TEPMETKO HUMAN PRESCRIPTION DRUG LABEL 1 44087-5000 TABLET 225 mg ORAL NDA 31 sections