Chapter

Cysteine Proteases of Pathogenic Organisms

Volume 712 of the series Advances in Experimental Medicine and Biology pp 100-115

Cruzain

The Path from Target Validation to the Clinic
  • Mohammed SajidAffiliated withAfd. Parasitologie, Leiden University Medical Center
  • , Stephanie A. RobertsonAffiliated withSandler Center for Drug Discovery, University of California— San Francisco
  • , Linda S. BrinenAffiliated withSandler Center for Drug Discovery, University of California— San FranciscoDepartment of Cellular and Molecular Pharmacology, University of California— San Francisco
  • , James H. McKerrowAffiliated withSandler Center for Drug Discovery, University of California— San Francisco

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Abstract

Cruzain is the major papain-like cysteine protease of Trypanosoma cruzi, the etiological agent causing Chagas’ disease in humans in South America. Cruzain is indispensable for the survival and propagation of this protozoan parasite and therefore, it has attracted considerable interest as a potential drug target. This chapter charts the path from the initial identification of this proteases activity and its validation as a bone fide drug target to the arduous task of the discovery of an inhibitor targeting this protease and finally the path towards the clinic.