tepotinib   Click here for help

GtoPdb Ligand ID: 8293

Synonyms: compound 22 [PMID: 25736998] | EMD 1214063 | EMD-1214063 | MSC2156119 | MSC2156119J | Tepmetko®
Approved drug PDB Ligand
tepotinib is an approved drug (FDA, EMA & UK MHRA (2021))
Compound class: Synthetic organic
Comment: Tepotinib is a potent and selective, orally available inhibitor of MET tyrosine kinase [1]. It was designed to inhibit the pro-oncogenic signalling caused by MET gene alterations that occur in 3-5% of NSCLC cases, and which correlate with poor prognosis.

Novel tepotinib derivatives are being assessed for antiproliferative activity [4].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 6
Hydrogen bond donors 0
Rotatable bonds 7
Topological polar surface area 96.93
Molecular weight 492.23
XLogP 4.13
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES N#Cc1cccc(c1)c1ccc(=O)n(n1)Cc1cccc(c1)c1ncc(cn1)OCC1CCN(CC1)C
Isomeric SMILES N#Cc1cccc(c1)c1ccc(=O)n(n1)Cc1cccc(c1)c1ncc(cn1)OCC1CCN(CC1)C
InChI InChI=1S/C29H28N6O2/c1-34-12-10-21(11-13-34)20-37-26-17-31-29(32-18-26)25-7-3-5-23(15-25)19-35-28(36)9-8-27(33-35)24-6-2-4-22(14-24)16-30/h2-9,14-15,17-18,21H,10-13,19-20H2,1H3
InChI Key AHYMHWXQRWRBKT-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
Tepotinib (research code MSC2156119J) was advanced to clinical evaluations in patients with various types of solid tumours. Having already been designated for SAKIGAKE 'fast-track' evaluation in Japan (2018), Merck announced that the FDA had granted tepotinib 'Breakthrough Therapy Designation' for the treatment of metastatic NSCLC with MET exon 14-skipping alterations (September 2019). This latter designation was based on evidence from Phase 2 trial NCT02864992. Click here to link to ClinicalTrials.gov's full list of tepotinib studies.
Full FDA approval was granted in February 2021, as a treatment for metastatic NSCLC with MET exon 14-skipping alterations. EMA authorisation for this indication followed at the end of 2021.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
MET plays key roles in tumour cell proliferation, survival, invasion, metastasis and tumour angiogenesis, and it is overexpressed or mutated in many human malignancies including cancers of the lung, kidney, stomach, liver, and brain. Mutations include MET exon 14-skipping alterations and MET amplifications that correlate with poor prognosis. Tepotinib is designed to inhibit aberrant over-activity of MET in affected cancers to bring about anti-tumour effects.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02864992 Tepotinib Phase II in Non-small Cell Lung Cancer (NSCLC) Harboring MET Alterations Phase 2 Interventional EMD Serono 2-3
External links Click here for help
For extended ADME data see the following:

Electronic Medicines Compendium (eMC)
Drugs.com
European Medicines Agency (EMA)