Potency assay, off target (cells):
GSK215 was further assessed by multiplexed proteome dynamics profiling (mPDP): In mature proteins, GSK215 showed dose dependent degradation of FAK, with selective degradation observed up to 10 nM GSK215 after 6 h. At concentrations above 100 nM levels of additional mature proteins were reduced, primarily kinases CDK7, RPS6KA3, MET and GAK. All members of the CAK complex (CDK7, MNAT1 and CCNH) were degraded.
Probe Selectivity in
Cell:
After 24 h treatment, the selectivity of degradation for GSK215 was maintained up to 10 nM while at higher concentrations additional targets of induced degradation were observed, with pronounced downstream regulatory effects on nascent protein levels at 100 nM.
