Figure 4.
Prospective prediction identifies irreversible kinase inhibitors
(A) Chemical structures and in vitro kinase activity assay IC50 values for nine prospective covalentizer predictions. See Figure S2 for the parent compounds, pose predictions, and RMSD values.
(B) Dose-response curves for each of the nine compounds. Each compound was tested against its corresponding target kinase. For compound 1, n = 3; for compounds 2, 4, 5, and 9, n = 2; error bars represent standard deviation.
(C) Deconvoluted mass spectra obtained by intact protein LC/MS of recombinant ERK2 (10 μM) incubated with 100 μM of 1 or 2 for 3 h at room temperature, shows full irreversible binding by both compounds.