Protease inhibitors and their peptidomimetic derivatives as potential drugs.

Precise spatial and temporal regulation of proteolytic activity is essential to human physiology. Modulation of protease activity with synthetic peptidomimetic inhibitors has proven to be clinically useful for treating human immunodeficiency virus (HIV) and hypertension and shows potential for medicinal application in cancer, obesity, cardiovascular, inflammatory, neurodegenerative diseases, and various infectious and parasitic diseases. Exploration of natural inhibitors and synthesis of peptidomimetic molecules has provided many promising compounds performing successfully in animal studies. Several protease inhibitors are undergoing further evaluation in human clinical trials. New research strategies are now focusing on the need for improved comprehension of protease-regulated cascades, along with precise selection of targets and improved inhibitor specificity. It remains to be seen which second generation agents will evolve into approved drugs or complementary therapies.