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Atlas / Drug / Tepotinib

Tepotinib

drug
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Also known as EMD 1214063Emd-1214063EMD1214063MSC-2156119MSC-2156119JMSC2156119TEPOTINIB_EMD-1214063

Summary

Tepotinib (CHEMBL3402762) is an approved small molecule (ATC L01EX21) targeting MET; indicated across 8 conditions including neoplasm and non-small cell lung carcinoma; with CIViC clinical evidence for 7 variant-indication associations (e.g. MET Exon 14 Skipping Mutation in lung non-small cell carcinoma).

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: L01EX21
  • Targets: 1 (MET)
  • Indications: 8 conditions
  • Clinical trials: 24
  • Precision-oncology evidence (CIViC): 7 variant–indication associations
  • Chemistry: 492.6 Da · C29H28N6O2

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL3402762
NameTepotinib
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID25171648
ATCL01EX21
Molecular formulaC29H28N6O2
Molecular weight492.6
InChIKeyAHYMHWXQRWRBKT-UHFFFAOYSA-N

SMILES: CN1CCC(CC1)COC2=CN=C(N=C2)C3=CC=CC(=C3)CN4C(=O)C=CC(=N4)C5=CC=CC(=C5)C#N

IUPAC name: 3-[1-[[3-[5-[(1-methylpiperidin-4-yl)methoxy]pyrimidin-2-yl]phenyl]methyl]-6-oxopyridazin-3-yl]benzonitrile

Also known as: EMD 1214063, Emd-1214063, EMD-1214063, EMD1214063, MSC-2156119, MSC-2156119J, MSC2156119, Tepotinib, TEPOTINIB, TEPOTINIB_EMD-1214063

Parent form; salt/anhydrous children: CHEMBL4594292

Patent coverage: 537 distinct patent families (1,276 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,257 (99%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
METMET proto-oncogene, receptor tyrosine kinaseInhibition8.522.4%P08581

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Hepatocyte growth factor receptor, Ribosyldihydronicotinamide dehydrogenase [quinone].

Bioactivity

ChEMBL activities: 8 potent at pChembl ≥ 5 of 8 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
MET9.05IC500.9nMCHEMBL_ACT_29320099
MET9Kd1nMCHEMBL_ACT_17919103
MET8.52IC503nMCHEMBL_ACT_16466235
MET8.51IC503.1nMCHEMBL_ACT_24672080
MET8.4IC504nMCHEMBL_ACT_25527164
MET8.05IC509nMCHEMBL_ACT_25881925
MET7.92IC5012nMCHEMBL_ACT_15165455
NQO26.06Kd875nMCHEMBL_ACT_17922440

Target pathways

Aggregated over 1 target gene(s): MET.

Top Reactome pathways

44 total, by targets touching each:

PathwayTargetsGenes
PIP3 activates AKT signaling1MET
Developmental Biology1MET
Signal Transduction1MET
Disease1MET
Negative regulation of the PI3K/AKT network1MET
Generic Transcription Pathway1MET
PI3K/AKT Signaling in Cancer1MET
Constitutive Signaling by Aberrant PI3K in Cancer1MET
Semaphorin interactions1MET
Sema4D in semaphorin signaling1MET
Sema4D mediated inhibition of cell attachment and migration1MET
Axon guidance1MET
Diseases of signal transduction by growth factor receptors and second messengers1MET
Infectious disease1MET
RAF/MAP kinase cascade1MET
MAPK family signaling cascades1MET
MAPK1/MAPK3 signaling1MET
Signaling by MET1MET
MET Receptor Activation1MET
Negative regulation of MET activity1MET
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling1MET
RNA Polymerase II Transcription1MET
Gene expression (Transcription)1MET
MET activates RAS signaling1MET
MET activates PI3K/AKT signaling1MET
MET activates PTPN111MET
MET activates PTK2 signaling1MET
InlB-mediated entry of Listeria monocytogenes into host cell1MET
MET interacts with TNS proteins1MET
MET activates RAP1 and RAC11MET

Dominant GO biological processes

GO termTargets
endothelial cell morphogenesis1
liver development1
cell surface receptor signaling pathway1
cell surface receptor protein tyrosine kinase signaling pathway1
negative regulation of autophagy1
neuron differentiation1
pancreas development1
positive regulation of transcription by RNA polymerase II1
hepatocyte growth factor receptor signaling pathway1
branching morphogenesis of an epithelial tube1
positive chemotaxis1
excitatory postsynaptic potential1
semaphorin-plexin signaling pathway1
negative regulation of hydrogen peroxide-mediated programmed cell death1
positive regulation of endothelial cell chemotaxis1

Indications & clinical

Indications

8 indications (2 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
neoplasm4MONDO:0005070EFO:0000616
non-small cell lung carcinoma2MONDO:0005233EFO:0003060
colorectal neoplasm2MONDO:0005335EFO:0004142
lung adenocarcinoma2MONDO:0005061EFO:0000571
hepatocellular carcinoma1MONDO:0007256EFO:0000182
liver disorder1MONDO:0005154EFO:0001421
brain neoplasm1MONDO:0021211EFO:0003833

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 24.

Phase distribution

PhaseTrials
PHASE29
PHASE19
PHASE1/PHASE25
PHASE31

Top trials by phase / activity

NCTPhaseStatusTitle
NCT06908993PHASE3RECRUITINGTepotinib vs Standard Treatment in Patients With Advanced MET Exon 14 Mutated Non-Small Cell Lung Cancer Previously Treated
NCT02864992PHASE2ACTIVE_NOT_RECRUITINGTepotinib Phase II in NSCLC Harboring MET Alterations (VISION)
NCT02925234PHASE2RECRUITINGThe Drug Rediscovery Protocol (DRUP Trial)
NCT03940703PHASE2ACTIVE_NOT_RECRUITINGA Study of Tepotinib Plus Osimertinib in Osimertinib Relapsed MET Amplified NSCLC (INSIGHT 2)
NCT05159245PHASE2RECRUITINGThe Finnish National Study to Facilitate Patient Access to Targeted Anti-cancer Drugs
NCT06031688PHASE2RECRUITINGTargeted Treatment for Advanced Non-Small Cell Lung Cancer That Has a MET Exon 14 Skipping Gene Change (An Expanded Lung-MAP Treatment Trial)
NCT06083857PHASE1/PHASE2ACTIVE_NOT_RECRUITINGPhI/II Study of Amivantamab and Tepotinib Combo in MET-altered Non-small Cell Lung Cancer
NCT06106802PHASE2RECRUITINGLazertinib & Tepotinib for EGFR Mutant NSCLC in MET Overexpressed or Amplified Who Progressed After Lazertinib Treatment
NCT01982955PHASE1/PHASE2COMPLETEDTepotinib With Gefitinib in Participants With Locally Advanced or Metastatic NSCLC (INSIGHT)
NCT01988493PHASE1/PHASE2COMPLETEDEfficacy, Safety, and Pharmacokinetic of MSC2156119J in Asian Participants With Hepatocellular Carcinoma
NCT02115373PHASE1/PHASE2COMPLETEDc-Met Second-Line Hepatocellular Carcinoma
NCT04515394PHASE2TERMINATEDStudy of Tepotinib Combined With Cetuximab in Participants With Left-Sided RAS/BRAF Wild Type Metastatic Colorectal Cancer (PERSPECTIVE)
NCT04591431PHASE2UNKNOWNThe Rome Trial From Histology to Target: the Road to Personalize Target Therapy and Immunotherapy
NCT04647838PHASE2UNKNOWNTepotinib in Solid Tumors Harboring MET Alterations
NCT04739358PHASE1/PHASE2TERMINATEDCNS Dose Escalation/Expansion of Tepotinib in MET-driven NSCLC
NCT05782361PHASE1ACTIVE_NOT_RECRUITINGPOTENT - Tepotinib in Combination With Pembrolizumab in NSCLC
NCT03492437PHASE1COMPLETEDEffect of Tepotinib on the PK of the P-gp Substrate Dabigatran Etexilate
NCT03531762PHASE1COMPLETEDEffect of a Proton Pump Inhibitor on the PK of Tepotinib
NCT03546608PHASE1COMPLETEDTepotinib Hepatic Impairment Trial
NCT03628339PHASE1COMPLETEDEffect of Tepotinib on PK of CYP3A Substrate Midazolam
NCT03629223PHASE1COMPLETEDBioequivalence of TF3 and TF2 and Effect of Food on the PK of Tepotinib
NCT04204902PHASE1COMPLETEDBioequivalence of 5 Tablets of 100 mg Versus 2 Tablets of 250 mg TF3 of Tepotinib
NCT05120960PHASE1WITHDRAWNA Phase 1a/1b Study to Determine the Recommended Phase 2 Dose, of Tepotinib in Participants With MET Alterations and Brain Tumors
NCT05213481PHASE1COMPLETEDTepotinib Drug-Drug Interaction Study With Carbamazepine in Healthy Participants

Clinical evidence (CIViC)

Variant × indication × effect (7 predictive associations from 15 curated evidence items):

VariantIndicationEffectTherapyLevelCIViC
MET Exon 14 Skipping MutationLung Non-small Cell CarcinomaSensitivity/ResponseTepotinibCIViC AEID11766 +3
EGFR Mutation AND ( MET Amplification OR MET Overexpression )Lung Non-small Cell CarcinomaSensitivity/ResponseTepotinib + GefitinibCIViC BEID11456
MET Exon 14 Skipping MutationLung AdenocarcinomaSensitivity/ResponseTepotinibCIViC CEID11464 +3
MET Exon 14 Skipping Mutation AND CD274 OverexpressionLung AdenocarcinomaSensitivity/ResponseTepotinibCIViC CEID11460 +2
EGFR L858R AND EGFR T790M AND MET Exon 14 Skipping MutationLung AdenocarcinomaSensitivity/ResponseTepotinibCIViC CEID11486
MET Splice Site (c.3028+2T>C)Lung AdenocarcinomaSensitivity/ResponseCapmatinib + TepotinibCIViC CEID11412
MET H1094LCancerSensitivity/ResponseTepotinibCIViC DEID7958

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

83 molecules share ≥1 primary target. Top 60 by shared-target count:

MoleculeSourceStatusShared targets
AFATINIBChEMBL + PubChemPhase 4 (approved)MET
CRIZOTINIBChEMBL + PubChemPhase 4 (approved)MET
PAZOPANIBChEMBL + PubChemPhase 4 (approved)MET
AFATINIB DIMALEATEChEMBLPhase 4 (approved)MET
AXITINIBChEMBLPhase 4 (approved)MET
BOSUTINIBChEMBLPhase 4 (approved)MET
BRIGATINIBChEMBLPhase 4 (approved)MET
CABOZANTINIBChEMBLPhase 4 (approved)MET
CABOZANTINIB S-MALATEChEMBLPhase 4 (approved)MET
CAPMATINIBChEMBLPhase 4 (approved)MET
CERITINIBChEMBLPhase 4 (approved)MET
DABRAFENIBChEMBLPhase 4 (approved)MET
ENSARTINIBChEMBLPhase 4 (approved)MET
ENTRECTINIBChEMBLPhase 4 (approved)MET
ERLOTINIBChEMBLPhase 4 (approved)MET
FEDRATINIBChEMBLPhase 4 (approved)MET
GEFITINIBChEMBLPhase 4 (approved)MET
INFIGRATINIBChEMBLPhase 4 (approved)MET
MIDOSTAURINChEMBLPhase 4 (approved)MET
NERATINIBChEMBLPhase 4 (approved)MET
NINTEDANIBChEMBLPhase 4 (approved)MET
PALBOCICLIBChEMBLPhase 4 (approved)MET
SORAFENIBChEMBLPhase 4 (approved)MET
SUNITINIBChEMBLPhase 4 (approved)MET
TIVOZANIBChEMBLPhase 4 (approved)MET
VANDETANIBChEMBLPhase 4 (approved)MET
CANERTINIBChEMBLPhase 3MET
CEDIRANIBChEMBLPhase 3MET
DACTOLISIBChEMBLPhase 3MET
ENZASTAURINChEMBLPhase 3MET
EPIGALOCATECHIN GALLATEChEMBLPhase 3MET
LESTAURTINIBChEMBLPhase 3MET
LINIFANIBChEMBLPhase 3MET
LINSITINIBChEMBLPhase 3MET
POZIOTINIBChEMBLPhase 3MET
QUERCETINChEMBLPhase 3MET
RIGOSERTIBChEMBLPhase 3MET
SAVOLITINIBChEMBLPhase 3MET
SITRAVATINIBChEMBLPhase 3MET
TIVANTINIBChEMBLPhase 3MET
ALTIRATINIBChEMBLPhase 2MET
AMG-208ChEMBLPhase 2MET
AMG-337ChEMBLPhase 2MET
AT-9283ChEMBLPhase 2MET
BEMCENTINIBChEMBLPhase 2MET
BI-2536ChEMBLPhase 2MET
BMS-754807ChEMBLPhase 2MET
BMS-777607ChEMBLPhase 2MET
CENISERTIBChEMBLPhase 2MET
CEP-32496ChEMBLPhase 2MET
DALMELITINIBChEMBLPhase 2MET
DECERNOTINIBChEMBLPhase 2MET
DEFOSBARASERTIBChEMBLPhase 2MET
ELLAGIC ACIDChEMBLPhase 2MET
ELZOVANTINIBChEMBLPhase 2MET
ENVONALKIBChEMBLPhase 2MET
FORETINIBChEMBLPhase 2MET
GLESATINIBChEMBLPhase 2MET
GOLVATINIBChEMBLPhase 2MET
GUMARONTINIBChEMBLPhase 2MET

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot