Development of cysteine protease inhibitors as chemotherapy for parasitic diseases: insights on safety, target validation, and mechanism of action.
Cysteine proteases have been identified as promising targets for the development of antiparasitic chemotherapy. An attractive aspect of these enzymes is their widespread importance in both protozoan and helminth parasites of domestic animals and humans. Concerns about the ability to selectively inhibit parasite proteases without affecting host homologues have been addressed in recent studies of Trypanosoma cruzi and Plasmodium falciparum. Significant data on half-life, metabolism, pharmacokinetics and safety have been accumulated. Differential uptake of proteases by parasitic organisms versus host cells, and relatively less redundancy in parasite protease gene families, may be two factors which contribute to the successful treatment of animal models of infection.
McKerrow
J H
JH
Department of Pathology, UCSF/VA Medical Center, San Francisco, CA 94121, USA. jmck@cgl.ucsf.edu
D000818:Animals; D000977:Antiparasitic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000981:Antiprotozoal Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015853:Cysteine Proteinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D056890:Eukaryota / Q000187:drug effects; D006373:Helminthiasis / Q000188:drug therapy; D006376:Helminths / Q000187:drug effects; D006801:Humans; D010272:Parasitic Diseases / Q000188:drug therapy*; D011528:Protozoan Infections / Q000188:drug therapy*; D012556:Schistosomicides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
D000977:Antiparasitic Agents; D000981:Antiprotozoal Agents; D015853:Cysteine Proteinase Inhibitors; D012556:Schistosomicides