lenvatinib   Click here for help

GtoPdb Ligand ID: 7426

Synonyms: E 7080 | ER-203492-00 | Kisplyx® | Lenvima®
Approved drug PDB Ligand
lenvatinib is an approved drug (FDA & EMA (2015))
Compound class: Synthetic organic
Comment: Lenvatinib is a potent inhibitor of VEGFR-2 (KDR) and VEGFR-3 (FLT4) [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

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View more information in the IUPHAR Pharmacology Education Project: lenvatinib

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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 3
Rotatable bonds 8
Topological polar surface area 115.57
Molecular weight 426.11
XLogP 2.47
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES COc1cc2nccc(c2cc1C(=O)N)Oc1ccc(c(c1)Cl)NC(=O)NC1CC1
Isomeric SMILES COc1cc2nccc(c2cc1C(=O)N)Oc1ccc(c(c1)Cl)NC(=O)NC1CC1
InChI InChI=1S/C21H19ClN4O4/c1-29-19-10-17-13(9-14(19)20(23)27)18(6-7-24-17)30-12-4-5-16(15(22)8-12)26-21(28)25-11-2-3-11/h4-11H,2-3H2,1H3,(H2,23,27)(H2,25,26,28)
InChI Key WOSKHXYHFSIKNG-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Lenvatinib's first approval (in 2015) was for use in treating patients with progressive, differentiated thyroid cancer.
Marketed formulations contain lenvatinib mesylate (PubChem CID 11237762).
In May 2016, the US FDA expanded approval to include treatment (in combination with everolimus) of advanced renal cell carcinoma following one prior anti-angiogenic therapy. FDA approval was further expanded in August 2018 to include use as a first-line treatment for unresectable hepatocellular carcinoma (HCC), based on results from trial NCT01761266 [1]. These results showed that lenvatinib was non-inferior to sorafenib in these patients. In Europe lenvatinib was granted EMA orphan designation as an HCC therapy in 2015.
Visit ClinicalTrials.gov to view currently registered drug trials assessing lenvatinib's effectiveness in treating additional types of cancer.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Lenvatinib is an inhibitor of all three VEGFR tyrosine kinases [2]. Inhibits vascular endothelial growth factor (VEGF)-stimulated neo-angiogenesis and may therefore reduce the vascularisation which underpins and supports tumour development and growth.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01761266 A Multicenter, Open-Label, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib (E7080) Versus Sorafenib in First-line Treatment of Participants With Unresectable Hepatocellular Carcinoma Phase 3 Interventional Eisai Inc.
External links Click here for help
For extended ADME data see the following:

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