title: Cruzain : the path from target validation to the clinic.
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.
authors.affiliation: Afd. Parasitologie, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Sajid
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Robertson
authors.forename: Linda S
authors.initials: LS
authors.lastname: Brinen
authors.forename: James H
authors.initials: JH
authors.lastname: McKerrow
mesh_terms: D000595:Amino Acid Sequence; D014355:Chagas Disease / Q000188:drug therapy / Q000469:parasitology; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004151:Dipeptides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008969:Molecular Sequence Data; D010649:Phenylalanine / Q000031:analogs & derivatives; D010879:Piperazines; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D015203:Reproducibility of Results; D014105:Tosyl Compounds; D057170:Translational Research, Biomedical; D014753:Vinyl Compounds / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D010879:Piperazines; D015800:Protozoan Proteins; D014105:Tosyl Compounds; D014753:Vinyl Compounds; C487484:N-pip-phenylalanine-homophenylalanine-vinyl sulfone phenyl; D010649:Phenylalanine; D003546:Cysteine Endopeptidases; C074032:cruzain, Trypanosoma cruzi