Description
WRR-483, an analogue of K-11777, is a potent and selective cysteine protease inhibitor with trypanocidal activity in cell culture and animal model with comparable efficacy to K11777. WRR-483 demonstrates good potency against cruzain with sensitivity to pH conditions and high efficacy in the cell culture assay. Furthermore, WRR-483 also eradicates parasite infection in a mouse model of acute Chagas' disease. WRR-483 binds covalently to the active site cysteine of the protease in a similar manner as other vinyl sulfone-based inhibitors. WRR-483 has potential to be developed as a treatment for Chagas' disease.
Uses
WRR-483 is an analog of K11777, an inhibitor of cruzain, used to inhibit the proliferation of Trypanosoma cruzi in cell culture. WRR-483 can eradicate parasitic infection in an acute Chagas disease mouse model. WRR-483 is an irreversible cysteine protease inhibitor that shows pH-dependent high affinity and potent trypanocidal activity against cruzain and T. cruzi infection, and is expected to inhibit Chagas disease.
References
[1] In Vitro and In Vivo Studies of the Trypanocidal Properties of WRR-483 against Trypanosoma cruzi
