Recent developments in cathepsin K inhibitor design.

Cathepsin K is abundantly and selectively expressed in osteoclasts where it plays a critical role in bone degradation. Cathepsin K inhibitors are the first antiresorptive agents that prevent bone loss while allowing bone formation to continue, thereby enhancing the quality and ultimately the strength of bone. The development of cathepsin K inhibitors requires appropriate cell-based assays and animal models. Advances in reversible cathepsin K inhibitor design from January 2004 are reviewed herein.