Figure 5
From: PKIS deep dive yields a chemical starting point for dark kinases and a cell active BRSK2 inhibitor
Structural- and activity-based comparisons of GW296115 to related compounds. (A) Structures of staurosporine, K-252a, midostaurin, SB 218078, bisindolylmaleimide IV, bisindolylmaleimide I, Gö 6983, Arcyriaflavin A, CDK4 inhibitor, Gö 6976, and K-252c versus GW296115. (B) Selectivity of compounds shown in panel A when profiled against 300 (staurosporine, K-252a, midostaurin, SB 218078, bisindolylmaleimide IV, bisindolylmaleimide I, Gö 6983, CDK4 inhibitor, and Gö 6976) or 403 (GW296115) wild type human kinases and NanoBRET data for most inhibitors in panel A (N = 3). (C) Alignment of key residues corresponding to CAMK kinases potently inhibited by GW296115 and CHEK1. Residues colored green demonstrate homology shared with BRSK2 and residue numbers listed below correspond with those discussed with respect to SB 218078 binding to CHEK1 (also boxed). (D) Inhibition data corresponding with those CAMK kinases (and CHEK1) included in profiling of inhibitors listed in panel A. Python version 3.8 was used to make heatmap in (D).
