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J Med Chem. 2002 Dec 5;45(25):5471-82.

Design and synthesis of dipeptide nitriles as reversible and potent Cathepsin S inhibitors.

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Boehringer Ingelheim Pharmaceuticals, Inc. 900 Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877-0368, USA.

Erratum in

  • J Med Chem. 2003 Feb 27;46(5):882.. Giradot Marc [corrected to Girardot Marc].


The specificity of the immune response relies on processing of foreign proteins and presentation of antigenic peptides at the cell surface. Inhibition of antigen presentation, and the subsequent activation of T-cells, should, in theory, modulate the immune response. The cysteine protease Cathepsin S performs a fundamental step in antigen presentation and therefore represents an attractive target for inhibition. Herein, we report a series of potent and reversible Cathepsin S inhibitors based on dipeptide nitriles. These inhibitors show nanomolar inhibition of the target enzyme as well as cellular potency in a human B cell line. The first X-ray crystal structure of a reversible inhibitor cocrystallized with Cathepsin S is also reported.

[Indexed for MEDLINE]

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