Serentrix is developing compounds for multiple indications that involve TRPV1 receptors. NSAIDs (non-steroidal anti-inflammatory drugs), opiates and other analgesics are useful drugs for many patients, but exhibit dose-limiting side effects, inadequate tolerability profiles and diminished efficacy over time. Consequently, pain is often under treated.

TRPV1 is perhaps the most important signal integrator in sensory nociceptors, is well established as an intriguing novel target for the treatment of pain. Extensive preclinical profiling of small-molecule inhibitors of TRPV1 provides intriguing evidence that TRPV1 blockade can be a useful therapeutic approach for inflammatory, and possibly neuropathic pain.

TRPV1 antagonism represents one of several novel mechanistic approaches to pain relief that might qualify as the next-generation analgesic. But although most of the drugs in development target the inflammatory system and the propagation and transmission of signals to the spinal cord, TRPV1 antagonists target the key mediator of nociceptive transduction. Because of TRPV1’s integrative signaling properties in response to inflammatory stimuli, TRPV1 antagonists are predicted to inhibit the sensation of ongoing or burning pain (spontaneous pain) that is reported by patients suffering from chronic pain, therefore, offering an unprecedented advantage in selectively inhibiting painful signaling without mechanistic limitations.

Company’s lead product has been successfully tested in 91 human subjects in 3 separate phase 1 studies.

Ref.: The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist proof of concept. Szallasi A., Cortright D.N., Blum C A., Eid S. R. Nature Reviews, Drug Discovery, Vol. 6, May 2007, page 357