3.1 NVP-BHG712 is a small molecule compound that targets CTSK.
We used a novel strategy to identify potential active small molecule compounds that target CTSK, and we ultimately identified NVP-BHG712 as a potential bioactive compound from the Selleckchem compound library.
As mentioned above in the Methods, the molecular docking method was used to search for small molecule compounds that target CTSK. First, we downloaded crystal conformations of human CTSK from the PDB database. According to the binding of the CTSK active pocket with known ligands, the ligands 7AS and OLC bind to CTSK in an L-shape, with part in the pocket and part extending upward, and the binding of the ligands KWZ and I37 to CTSK occurs in both upward and downward conformations (Fig. 1A, B). Analysis showed that I37 had the weakest binding strength among the four ligands because the molecule was small and the interaction with CTSK was weak, but its binding strength could reach an order of nM. Therefore, we selected these four molecular conformations of CTSK for molecular docking to search for new small molecule compounds that bind to CTSK. According to the results of molecular docking analysis with molDockTools software, a small molecule compound was identified to bind to the four conformations of CTSK (Fig. 1C), and the compound was NVP-BHG712 (Fig. 1D). Moreover, through a literature review, we did not find any reports of an effect of NVP-BHG712 on CTSK and osteoclast formation. Therefore, we next focused on the effects of NVP-BHG712 on CTSK and osteoclast formation.