Cysteine proteases as therapeutic targets

Protease-targeted drugs are not common, although metalloprotease inhibitors have been favored in recent years. Cysteine proteases of the papain superfamily have been viewed as less attractive drug targets until recently, due to the former view that they were unspecific and ubiquitously distributed. However, many novel findings on papain-like cysteine proteases have been made. Presently there are at least 12 human proteases of the papain family from which sequences have been obtained (cathepsins B, L, H, S, O, K, C, W, F, V(L2), Z(X) and bleomycin hydrolase). Several of these new enzymes have a restricted tissue distribution, which implies specific cellular functions, and thus would allow a specific targeting of there activities without interfering with the general lysosomal protein degradation. The cathepsins have been found to participate in a number of diseases such as osteoporosis, rheumatoid arthritis, osteoarthritis and cancer, as well as in immune response and neurodegeneration.