Fig. (6).

The binding of selected inhibitors to TNKS1/TNKS2. Inhibitors binding to the nicotinamide subsite: A) CMP8 (PDB ID 4BUD), B) CMP11 (PDB ID 4IUE), and C) the general phramacophore of the inhibitors binding to this site. Hydrogen bond interactions of the compounds are shown in dashed lines. Hydrophobic features are shown as spheres and π-π stacking features are black discs. Inhibitors binding mainly to the adenosine subsite are shown in D) G007- LK (PDB ID 4HYF) and E) WIKI4 (PDB ID 4BFP), together with F) showing the common pharmacophoric features at this site. Compounds spanning both sites G) CMP4b (PDB ID 4I9I) and H) NVP-TNKS656-analog (PDB ID 4LI8) are shown as well as I) the combined pharmacophoric features of the dual binders.