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.
Cathepsins are part of a larger enzyme family called proteases, which are well known therapeutic targets. Proteases selectively cleave proteins by cutting the peptide bonds that link specific amino acids. Proteases are involved in a wide range of biological processes which are relevant to human disease, and are the target of many successfully marketed therapies. Some examples of protease inhibitors that have become commercially successful drugs include angiotensin-converting enzyme inhibitors, human immunodeficiency virus protease inhibitors, hepatitis C protease inhibitors and Factor Xa inhibitors. There are at least 460 proteases in the human genome, 11 of which are cysteine cathepsin proteases, and we are currently focused on the development of inhibitors of two of these proteases, cathepsins S and B. Our employees and others have discovered that cathepsins S and B play critical roles in chronic conditions, including neuropathic pain, autoimmune diseases and fibrosis. In addition, we believe our knowledge of cathepsin biology and the breadth, specificity and potency of our diverse inhibitor library will enable us to develop inhibitors that target other cysteine cathepsins that play a role in important diseases.
Cathepsins S and B are attractive targets due to their extensive biological validation and their well- defined sites for binding small-molecule drugs. Like other validated drug targets, such as kinases, G protein-coupled receptors, ion channels and hydrolases, cathepsins S and B play a critical role in a range of diseases. In contrast to such targets, cathepsins S and B are members of a relatively small family of proteases which are easily distinguished from one another. The smaller number of related family members and their unique structures enabled the development of our selective inhibitors that we believe will not interact with other proteases and thereby exhibit selectivity and safety.