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.