tamatinib   

GtoPdb Ligand ID: 5706

Synonyms: R 406 | R-406 | R406 free base
Compound class: Synthetic organic
Comment: Tamatinib (R406) is a potent ATP-competitive (Type I) Syk inhibitor. It is the active form of the prodrug fostamatinib.
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 7
Hydrogen bond donors 3
Rotatable bonds 7
Topological polar surface area 128.75
Molecular weight 470.17
XLogP 2.72
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES COc1cc(Nc2ncc(c(n2)Nc2ccc3c(n2)NC(=O)C(O3)(C)C)F)cc(c1OC)OC
Isomeric SMILES COc1cc(Nc2ncc(c(n2)Nc2ccc3c(n2)NC(=O)C(O3)(C)C)F)cc(c1OC)OC
InChI InChI=1S/C22H23FN6O5/c1-22(2)20(30)28-19-13(34-22)6-7-16(27-19)26-18-12(23)10-24-21(29-18)25-11-8-14(31-3)17(33-5)15(9-11)32-4/h6-10H,1-5H3,(H3,24,25,26,27,28,29,30)
InChI Key NHHQJBCNYHBUSI-UHFFFAOYSA-N
Bioactivity Comments
Autophosphorylation of FLT3 is inhibited by tamatinib [1]. Inhibition of RET by tamatinib is thought to be responsible for renal and ureteric agenesis observed in developmental toxicity tests carried out in rats and rabbits [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 Hs Inhibitor Inhibition 7.7 pKd - 3
pKd 7.7 (Kd 1.9x10-8 M) [3]
spleen associated tyrosine kinase Hs Inhibitor Inhibition 7.4 – 7.8 pIC50 - 1,4,6
pIC50 7.8 (IC50 1.7x10-8 M) [4]
Description: Measuring inhibition of the capacity of a truncated construct of Syk (aa 360-635) to phosphorylate a biotinylated peptide substrate.
pIC50 7.4 – 7.5 (IC50 4.1x10-8 – 3x10-8 M) [1,6]
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
ret proto-oncogene Hs Inhibitor Inhibition 8.3 pIC50 - 2
pIC50 8.3 (IC50 5x10-9 M) [2]