compound 6g [PMID: 30633509]   Click here for help

GtoPdb Ligand ID: 10194

Compound class: Synthetic organic
Comment: Compound 6g was desigend as a dual epidermal growth factor receptor (EGFR) kinase and tubulin polymerization inhibitor [1]. It binds to the colchicine site on tubulin which is expected to translate to antimitotic activity and it should mediate a vascular-disrupting effect via EGFR inhibition.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 3
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 93.74
Molecular weight 407.13
XLogP 4.01
No. Lipinski's rules broken 0
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Canonical SMILES COc1cc(cc(c1OC)OC)Nc1ncnc2c1sc(c2)c1ccc(cc1)C
Isomeric SMILES COc1cc(cc(c1OC)OC)Nc1ncnc2c1sc(c2)c1ccc(cc1)C
InChI InChI=1S/C22H21N3O3S/c1-13-5-7-14(8-6-13)19-11-16-21(29-19)22(24-12-23-16)25-15-9-17(26-2)20(28-4)18(10-15)27-3/h5-12H,1-4H3,(H,23,24,25)
Bioactivity Comments
Compound 6g inhibits EGFR kinase activity with an IC50 of 30 nM and inhibits tubulin assembly with an IC50 of 710 nM .[1]. It induces apoptosis and produces potent (1-20 nM IC50) cell growth inhibitory effects in vitro, across a range of cell lines.
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
epidermal growth factor receptor Hs Inhibitor Inhibition 7.5 pIC50 - 1
pIC50 7.5 (IC50 3x10-8 M) [1]