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.
Neuropathic pain originates from nerve damage and can be a chronic and debilitating condition. This nerve damage may arise from mechanical, immunological or chemical injury, including, for example, chemotherapy. A pivotal process involved in developing neuropathic pain is the release of fractalkine, a protein that triggers the release of inflammatory signals that in turn communicate a pain message to the neuron. Cathepsin S cleaves fractalkine from the membrane to which it is bound, releasing it to trigger inflammatory signals.
A compound such as VBY-036, which inhibits the activity of cathepsin S and blocks the release of fractalkine, should therefore prevent or substantially reduce pain. Many existing therapeutics directly inhibit nerve signal transmission, which may lead to serious side effects. We believe that inhibiting the cathepsin S pathway provides a fundamental advantage over current therapies because it reduces the source of the neuroinflammation that generates pain messages in the nervous system.