Cathepsins are a family of proteases that have been implicated in many diseases.
Virobay compounds are highly potent, orally active and drug-like; addressing common problems in the design of cathepsin inhibitors.
Autoimmune diseases, such as Crohn’s disease, SLE and psoriasis, occur when the body’s immune system mistakenly attacks healthy normal tissues. Cathepsin S performs a key step early in the development of autoimmune disease by activating a type of cell, CD4+ T, critical to the function of the immune system which is inappropriately activated in disease. When this step is blocked by a cathepsin S inhibitor, CD4+ T cells are not activated, and the autoimmune disease dependent on their activity is suppressed.
The specific step that cathepsin S performs is the cleavage of a protein called the invariant chain. Cleaving the invariant chain is a critical and necessary step in enabling the assembly of a specific cell surface protein receptor known as MHC Class II, which activates CD4+ T cells. Inhibition of cathepsin S activity will block this process and assembly of the receptor, preventing the activation of CD4+ T cells. We use biomarkers of this process to determine the level of cathepsin S inhibition and as such, guide dosing. Cathepsin S inhibition will not block other pathways of the immune system, including the pathways involved in the protective response against viruses. We believe that cathepsin S inhibitors such as VBY-036 will block the cleavage of the invariant chain, thereby suppressing autoimmune disease without fully suppressing the immune system.