TGR-1202 acts as an inhibitor of CK1ε. (A) Excerpt of kinome profiling data, showing the activity of various casein kinases when treated by 3 PI3Kδ inhibitors at the same condition of 1 μM, including TG, Ide, and duvelisib (Duv). The details are listed in supplemental Table 3. (B) Structural formulae of PF-4800567 and TGR-1202 with the CPA moiety circled, and central ring atoms numbered. The arrows denote the positions involved as hydrogen bonds donor (amine group) and acceptor (position 1). (C) Comparison of the cocrystallization of PF-4800567 and CK1ε to in silico docking of TGR-1202 in the active site binding pocket. (D) Interaction map of TGR-1202 with the active site amino acids of CK1ε with legend at the bottom. (E) Cell-free kinase activity assay of CK1ε measuring dose-activity curves of PF-4800567, TG, Ide, CUX-03173, and CUX-03166. EC₅₀ and R² values are listed in supplemental Figure 4F. (F) Cell-based autophosphorylation assay of CK1ε C terminus. LY7 cells were pretreated for 1 hour with the indicated drugs and then treated with the PP2A inhibitor calyculin-A (Caly A) for 0, 15, 30, and 60 minutes when lysates were collected and western blots were performed. CUX, CUX-03173; PF, PF4800567.