mivavotinib   Click here for help

GtoPdb Ligand ID: 9600

Synonyms: compound 3b [PMID: 27839918] | TAK-659 | TAK659
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Mivavotinib (TAK-659) an orally available inhibitor of spleen tyrosine kinase (SYK), which is in clinical development for solid tumour and lymphoma malignancies. We have drawn the structure as represented in [1].
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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 3
Rotatable bonds 3
Topological polar surface area 97.86
Molecular weight 344.18
XLogP 1.44
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 NC1CCCCC1Nc1nc(c2cnn(c2)C)c2c(c1F)CNC2=O
Isomeric SMILES N[C@H]1CCCC[C@H]1Nc1nc(c2cnn(c2)C)c2c(c1F)CNC2=O
InChI InChI=1S/C17H21FN6O/c1-24-8-9(6-21-24)15-13-10(7-20-17(13)25)14(18)16(23-15)22-12-5-3-2-4-11(12)19/h6,8,11-12H,2-5,7,19H2,1H3,(H,20,25)(H,22,23)/t11-,12+/m0/s1
InChI Key MJHOMTRKVMKCNE-NWDGAFQWSA-N
Bioactivity Comments
TAK-659 was chosen as the primary clinical lead from a set of SAR analogues as it has favourable kinase selectivity for SYK, exhibits a good in vitro profile, and is devoid of CYP or hERG liabilities [1]. The effect of TAK-659 on the proliferation and survival of chronic lymphocytic leukemia (CLL) cells is reported by Purroy et al. (2017) [2].
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
spleen associated tyrosine kinase Primary target of this compound Hs Inhibitor Inhibition 8.0 pEC50 - 1
⤷ pEC50 8.0 (EC50 9.8x10-9 M) [1]
Description: Cellular potency
spleen associated tyrosine kinase Primary target of this compound Hs Inhibitor Inhibition 8.5 pIC50 - 1
⤷ pIC50 8.5 (IC50 3.2x10-9 M) [1]
Description: Enzyme inhibition in vitro.
zeta chain of T cell receptor associated protein kinase 70 Hs Inhibitor Inhibition 7.1 pIC50 - 1
⤷ pIC50 7.1 (IC50 7.5x10-8 M) [1]
Description: Measured in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay.
Janus kinase 3 Hs Inhibitor Inhibition 6.9 pIC50 - 1
⤷ pIC50 6.9 (IC50 1.15x10-7 M) [1]
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
fms related receptor tyrosine kinase 3 Hs Inhibitor Inhibition 8.3 pIC50 - 1
⤷ pIC50 8.3 (IC50 4.6x10-9 M) [1]
Description: In vitro potency
kinase insert domain receptor Hs Inhibitor Inhibition 6.9 pIC50 - 1
⤷ pIC50 6.9 (IC50 1.35x10-7 M) [1]
Description: Measured in a caliper-based electrophoretic mobility shift assay.