Chronic Neuropathic Pain and Cathepsin S

Pain has been defined as ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage’ (International Association for the Study of Pain^®).  Neuropathic pain is pain associated with the nervous system.  Many instances of chronic neuropathic pain are a result of other conditions such as injury, cancer, viral infection (Herpes Zoster; Shingles); multiple sclerosis, diabetes, etc.  The incidence of chronic neuropathic pain is ~10 million in the USA (2005) and ~8 million in Europe; with an estimated global rate of ~8%. Recent advances in the elucidation of the molecular mechanism of chronic neuropathic pain have implicated cathepsin S as an essential mediator (Barclay, et al., (2007). Probe inhibitors of cathepsin S have demonstrated efficacy in a disease-related animal model of chronic neuropathic pain (Clark, et al., (2007).

General information on pain: link here

International Associated for the Study of Pain^®: link here

Amura has developed low nanomolar inhibitors of cathepsin S with excellent selectivity against other cathepsins and attractive drug-like properties, with AM-3840  identified as the development candidate. In an in vivo sciatic nerve ligature model, multiple compounds demonstrated a rapid and marked inhibition of mechanical hyperalgesia that was dose-dependant and fully reversible.  This candidate has the potential to be a first-in-class fast-acting oral agent for the relief of chronic neuropathic pain.

In addition to the in vivo PoC data, the quality of the molecules is confirmed by a comprehensive pre-clinical package which includes pharmacokinetic data, selectivity and safety assessment. The lead molecule and a first rate back-up molecule are now available for partnering.

These drugs are the product of Amura’s AMcore™ platform which  has reproducibly provided ‘fast-on, slow-off rate’ enzyme inhibitors with good pharmacokinetic half-lives and a very strong IP position. 

Full Compound Information Summaries are available under Confidentiality Agreement.