This molecule is recommended for isolated enzyme, cell, 3D-cell spheroid and animal work for the specific ALK mutant described (ALK L1196M). There is a convincing package of on- and off-target selectivity, cell, biophysical and mouse data. Multiple lines of evidence demonstrate direct inhibition of the enzyme (biochemical, competition experiments, biophysical and X-ray) and exceptional selectivity for this ATP-competitive kinase inhibitor (only 3 kinases - ALK, GAK, LTK are inhibited >50% at 10 nM across a 402 kinase panel). Extended exposure results from a single dose in mice (high 70% oral bioavailability with 8.6 h half life).
31 Dec 2016 )