Ligand id: 9222

Name: EAI045

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 5
Topological polar surface area 110.77
Molecular weight 383.07
XLogP 3.17
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

Bioactivity Comments
EAI045 inhibits L858R/T790M mutant EGFR with an IC50 of 3nM and is >1000-fold selective for this mutant compared to wild-type receptor [1]. In screening panels EAI045 did not inhibit any other kinases by >20% (at 1000nM EAI045), or show any liability against non-kinase targets. In animal models EAI045 is most effective in combination wih cetuximab, a monoclonal antibody which effectively blocks ligand-induced EGFR dimerization and enhances the population of receptor subunits susceptible to the allosteric inhibitor [1]. In xenograft models EAI045 is effective against EGFR(L858R/T790M/C797S) tumours, a mutation profile that is resistant to all currently available ATP-competitive EGFR tyrosine kinase inhibitors.