Cathespin S Inhibitors
Small Molecule Cathespin S Inhibitors
Cathepsin S, found in most antigen-presenting cells.
The enzyme Cathepsin S promotes the loading of peptide into the MHC Class II molecule's binding groove by cleaving a molecule called the invariant chain which initially occupies the groove. Studies performed have revealed that inhibitors of Cathepsin S prevent peptide loading and subsequent presentation to and activation of T-cells. Peptimmune has a proprietary position in this field.
Mechanism of Action
Cathepsin S inhibitors prevent the degradation of a molecule called the invariant chain. By preventing this degradation, Cathespin S inhibitors prevent the loading of autoantigenic peptides to the MHC class II (MHC II) molecule and subsequently the initialization of MHC II restricted T-cell recognition.
Preclinical Studies
A lead series compound has been examined in a murine model of RA. Prophylactic oral administration of the compound in type II collagen-induced arthritis significantly suppressed disease development as measured by inflammation of individual digits on all four limbs and paws. In addition, an oral therapeutic dosing regimen resulted in a significant reduction in paw volume. Although the studies were not designed to measure the specific toxicological effects of compound on animals, no compound-related adverse effects were observed during the experimental period. A candidate drug will be selected based upon its favorable potency, selectivity, oral bioavailability, toxicology profile, and bioactivity.
Peptimmune has licensed its proprietary intellectual property and technology to Medivir AB, a Stockholm-based medicinal chemistry/biotechnology company, on a worldwide basis.
