amuvatinib   Click here for help

GtoPdb Ligand ID: 7932

Synonyms: MP 470 | MP-470 | MP470
Compound class: Synthetic organic
Comment: Amuvatinib is an orally bioavailable, multitargeted receptor tyrosine kinase inhibitor. Some bioactivity data may be associated with the hydrochloride salt (PubChem CID 67254077).

amuvatinib is commercially available from our sponsors

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 5
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 107.98
Molecular weight 447.14
XLogP 3.86
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 S=C(N1CCN(CC1)c1ncnc2c1oc1c2cccc1)NCc1ccc2c(c1)OCO2
Isomeric SMILES S=C(N1CCN(CC1)c1ncnc2c1oc1c2cccc1)NCc1ccc2c(c1)OCO2
InChI InChI=1S/C23H21N5O3S/c32-23(24-12-15-5-6-18-19(11-15)30-14-29-18)28-9-7-27(8-10-28)22-21-20(25-13-26-22)16-3-1-2-4-17(16)31-21/h1-6,11,13H,7-10,12,14H2,(H,24,32)
InChI Key FOFDIMHVKGYHRU-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
A Phase 2 clinical trial for small cell lung cancer (in combination with platinum-etoposide chemotherapy) was registered with ClinicalTrials.gov, but details have not been updated since 2012.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Amuvatinib binds to and inhibits the activity of mutant forms of the stem cell factor receptor (c-Kit, mutant forms of which are often associated with tumor chemoresistance [2]), AXL [2] and other receptor tyrosine kinases, such as c-Met, Ret oncoprotein, and mutant forms of Flt3 and PDGFRα, which are frequently dysregulated in variety of tumours. In addition, this compound suppresses the induction of the DNA repair protein RAD51 recombinase (HGNC ID 9817), thereby potentiating the activities of DNA damage-inducing agents [3-4].