compound 8i [PMID: 22765894]   Click here for help

GtoPdb Ligand ID: 9905

Compound class: Synthetic organic
Comment: Compound 8i is a multi-target receptor tyrosine kinase inhibitor [1]. The chemical structure matches that ascribed to the Exelixis compound XL999 presented by MedKoo, but there is no peer reviewed confirmation of this nomenclature linkage.
Compound 8i does not alter c-MET activity, so its effects can be compared to those of foretinib and/or cabozantinib which are c-MET inhibitors, to help assess the contribition that inhibition of the different kinases makes to measured outcomes (e.g. antiproliferative effect).
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 3
Rotatable bonds 5
Topological polar surface area 73.05
Molecular weight 445.23
XLogP 3.77
No. Lipinski's rules broken 0
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Canonical SMILES CCN1CCC(CC1)Nc1ccc2c(c1)C(=C(c1ncc([nH]1)C)c1cccc(c1)F)C(=O)N2
Isomeric SMILES CCN1CCC(CC1)Nc1ccc2c(c1)/C(=C(/c1ncc([nH]1)C)\c1cccc(c1)F)/C(=O)N2
InChI InChI=1S/C26H28FN5O/c1-3-32-11-9-19(10-12-32)30-20-7-8-22-21(14-20)24(26(33)31-22)23(25-28-15-16(2)29-25)17-5-4-6-18(27)13-17/h4-8,13-15,19,30H,3,9-12H2,1-2H3,(H,28,29)(H,31,33)/b24-23-
Bioactivity Comments
Compound 8i is potent inhibitor of key receptor tyrosine kinases (e.g. FGFR, VEGFRs and PDGFRs) that are implicated in the development and maintenance of tumour vasculature, and in the proliferation of some tumour cell types. Potent inhibition of FLT3 by compound 8i may be effective in down-modulating leukemia cell proliferation in AML.
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 9.1 pIC50 - 2
pIC50 9.1 (IC50 8x10-10 M) [2]
platelet derived growth factor receptor beta Hs Inhibitor Inhibition 8.8 pIC50 - 2
pIC50 8.8 (IC50 1.5x10-9 M) [2]
platelet derived growth factor receptor alpha Hs Inhibitor Inhibition 8.7 pIC50 - 1
pIC50 8.7 (IC50 2x10-9 M) [1]
fms related receptor tyrosine kinase 4 Hs Inhibitor Inhibition 8.5 pIC50 - 2
pIC50 8.5 (IC50 3x10-9 M) [2]
kinase insert domain receptor Hs Inhibitor Inhibition 8.4 – 8.6 pIC50 - 1-2
pIC50 8.6 (IC50 2.6x10-9 M) [2]
pIC50 8.4 (IC50 4x10-9 M) [1]
AXL receptor tyrosine kinase Hs Inhibitor Inhibition 8.3 pIC50 - 2
pIC50 8.3 (IC50 4.6x10-9 M) [2]
fibroblast growth factor receptor 1 Hs Inhibitor Inhibition 8.2 – 8.4 pIC50 - 1-2
pIC50 8.4 (IC50 4x10-9 M) [1]
pIC50 8.2 (IC50 6.2x10-9 M) [2]
KIT proto-oncogene, receptor tyrosine kinase Hs Inhibitor Inhibition 7.9 pIC50 - 2
pIC50 7.9 (IC50 1.38x10-8 M) [2]
fms related receptor tyrosine kinase 1 Hs Inhibitor Inhibition 7.5 – 7.7 pIC50 - 1-2
pIC50 7.7 (IC50 2x10-8 M) [1]
pIC50 7.5 (IC50 2.9x10-8 M) [2]
macrophage stimulating 1 receptor Hs Inhibitor Inhibition 6.9 pIC50 - 2
pIC50 6.9 (IC50 1.24x10-7 M) [2]
TEK receptor tyrosine kinase Hs Inhibitor Inhibition 6.6 pIC50 - 2
pIC50 6.6 (IC50 2.7x10-7 M) [2]
MET proto-oncogene, receptor tyrosine kinase Hs Inhibitor Inhibition 6.3 pIC50 - 2
pIC50 6.3 (IC50 4.63x10-7 M) [2]