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.
Liver fibrosis is the scarring of the liver in response to chronic injury or disease. While such a process is normal in the context of wound healing, it becomes pathological when the liver suffers repeated injuries and scar tissue accumulates to the point of causing dysfunction. These repeat injuries arise from various sources such as chronic infection with Hepatitis B or HCV, high fat diets, excessive alcohol or other chemical exposures or autoimmune attacks. Cathepsin B activity plays a role in both triggering the fibrotic process and in initiating the destruction of important liver cells. The combination of these activities results in the deposition of fibrotic scar tissue. Over time, unconstrained cathepsin B activity can lead to fibrotic liver diseases and cirrhosis of the liver. We believe inhibition of this activity may reduce and potentially reverse liver fibrosis in patients with these chronic liver diseases.
PBC is a chronic liver disease in which the small bile ducts of the liver are slowly destroyed by chronic autoimmune attack. Significant damage to the bile ducts is accompanied by liver fibrosis which can, in turn, advance to cirrhosis and liver failure. As described in the previous paragraphs, cathepsin S plays a role in autoimmune disease and cathepsin B in fibrosis. We believe blocking their activity may be effective in treating PBC by suppressing the autoimmune attack on the liver and reducing or even reversing liver fibrosis.