capmatinib   Click here for help

GtoPdb Ligand ID: 7904

Synonyms: INC280 | INCB28060 | Tabrecta®
Approved drug
capmatinib is an approved drug (FDA (2020), EMA (2022))
Compound class: Synthetic organic
Comment: Capmatinib (NCB28060) is a novel, oral, ATP-competitive inhibitor of c-MET that was developed by Novartis [2].
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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 1
Rotatable bonds 5
Topological polar surface area 85.07
Molecular weight 412.14
XLogP 3.28
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 CNC(=O)c1ccc(cc1F)c1cnc2n(n1)c(cn2)Cc1ccc2c(c1)cccn2
Isomeric SMILES CNC(=O)c1ccc(cc1F)c1cnc2n(n1)c(cn2)Cc1ccc2c(c1)cccn2
InChI InChI=1S/C23H17FN6O/c1-25-22(31)18-6-5-16(11-19(18)24)21-13-28-23-27-12-17(30(23)29-21)10-14-4-7-20-15(9-14)3-2-8-26-20/h2-9,11-13H,10H2,1H3,(H,25,31)
InChI Key LIOLIMKSCNQPLV-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
Capmatinib was advanced to clinical trial for various types of cancer either alone or in combination with other antineoplastics. Targeted indications include recurrent gliobastoma, advanced hepatocellular carcinoma, advanced non-small cell lung cancer, papillary renal cell cancer and advanced BRAF melanoma. For example capmatinib + nivolumab (an approved anti-PD-1 mAb) is being evaluated in study NCT02323126 (Phase 2 for previously treated NSCLC). NCT02795429 (Phase 1/2 in advanced HCC) is evaluating capmatinib + spartalizumab (PDR001, an investigational anti-PD-1 mAb). Click here to link to ClinicalTrials.gov's complete listing of capmatinib trials.
In March 2019, the FDA granted capmatinib orphan drug designation for the treament of MET-mutated advanced NSCLC [1]. Full authorisaton, delivered through the FDA's accelerated approval process, was granted in May 2020, with capmatinib indicated for metastatic NSCLC with a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping. The FoundationOne CDx assay was approved at the same time as a companion diagnostic that must be used to confirm the presence of mutation. EMA authorisation as a NSCLC treatment followed in 2022.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02323126 Study of Efficacy and Safety of Nivolumab in Combination With EGF816 and of Nivolumab in Combination With INC280 in Patients With Previously Treated Non-small Cell Lung Cancer Phase 2 Interventional Novartis
NCT02795429 Phase Ib/II Study of INC280 + PDR001 or PDR001 Single Agent in Advanced HCC Phase 1/Phase 2 Interventional Novartis