Inhibition of human cathepsin K by 22. Top: Monitoring
of the cathepsin K-catalyzed hydrolysis of Z-Leu-Arg-AMC in the presence
of increasing concentrations of compound 22 (closed circles,
0 pM; open circles, 400 pM; closed squares, 800 pM; open squares,
1200 pM; closed triangles, 1600 pM; open triangles, 2000 pM). Fluorescence
emission at 440 nm was measured after excitation at 360 nm. Bottom:
Plot of the rates obtained in duplicate measurements versus concentrations
of 22. Nonlinear regression gave an IC50 value
of 158 (±14) pM. Inset: Plot of the first-order rate constants kobs versus concentrations of 22. Linear regression gave a value kon/(1
+ [S]/Km) of 1.33 (±0.15)
× 10–6 pM–1 s–1.