savolitinib   Click here for help

GtoPdb Ligand ID: 9918

Synonyms: AZD-6094 | AZD6094 | compound 28 [PMID: 25148209] | HMPL-504 | HMPL504 | Orpathys® | volitinib
Approved drug PDB Ligand
savolitinib is an approved drug (China (2021))
Compound class: Synthetic organic
Comment: Savolitinib is a potent and selective, ATP-competitive mesenchymal-epithelial transition factor (c-Met) inhibitor that was designed for anti-cancer potential [2]. In this discovery report it was called volitinib, but the designated INN is savolitinib. Research codes are HMPL-504 and AZD6094.
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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 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 0
Rotatable bonds 3
Topological polar surface area 91.61
Molecular weight 345.15
XLogP 2.77
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 Cn1ncc(c1)c1cnc2c(n1)n(nn2)C(c1ccc2n(c1)ccn2)C
Isomeric SMILES Cn1ncc(c1)c1cnc2c(n1)n(nn2)[C@H](c1ccc2n(c1)ccn2)C
InChI InChI=1S/C17H15N9/c1-11(12-3-4-15-18-5-6-25(15)10-12)26-17-16(22-23-26)19-8-14(21-17)13-7-20-24(2)9-13/h3-11H,1-2H3/t11-/m0/s1
InChI Key XYDNMOZJKOGZLS-NSHDSACASA-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/)
Bioactivity Comments
Savolitinib is reported to show exquisite selectivity for c-Met (including Met mutations) amongst 274 kinases tested [2]. At 1 μM savolitinib PAK3 is the only kinase tested that is inhibited by >50%, and is only 51% inhibited at this concentration of inhibitor.
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
MET proto-oncogene, receptor tyrosine kinase Hs Inhibitor Inhibition 8.3 pIC50 - 2
⤷ pIC50 8.3 (IC50 5x10-9 M) [2]