JBJ-09-063   Click here for help

GtoPdb Ligand ID: 12001

Compound class: Synthetic organic
Comment: JBJ-09-063 is a negative allosteric modulator (inhibitor) of mutant-epidermal growth factor receptor (EGFR) in tumours [1]. It was designed to provide efficacy in in EGFR-mutant cancers with resistance to existing ATP-competitive receptor tyrosine kinase inhibitors.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 7
Topological polar surface area 114.01
Molecular weight 556.19
XLogP 4.12
No. Lipinski's rules broken 0
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Canonical SMILES CN1CCC(CC1)c1ccc(cc1)c1ccc2c(c1)C(=O)N(C2)C(c1cc(F)ccc1O)C(=O)Nc1nccs1
Isomeric SMILES CN1CCC(CC1)c1ccc(cc1)c1cc2c(CN(C(C(=O)Nc3nccs3)c3c(O)ccc(F)c3)C2=O)cc1
InChI InChI=1S/C31H29FN4O3S/c1-35-13-10-21(11-14-35)19-2-4-20(5-3-19)22-6-7-23-18-36(30(39)25(23)16-22)28(26-17-24(32)8-9-27(26)37)29(38)34-31-33-12-15-40-31/h2-9,12,15-17,21,28,37H,10-11,13-14,18H2,1H3,(H,33,34,38)
Bioactivity Comments
JBJ-09-063 is effective in vivo in osimertinib-resistant tumour models [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
epidermal growth factor receptor Hs Allosteric modulator Negative 10.1 pIC50 - 1
pIC50 10.1 (IC50 8.3x10-11 M) [1]
Description: Inhibition of enzyme activity of triple mutant EGFR L858R/T790M/C797S