The National Institute on Drug Abuse (NIDA) - one of the US National Institutes of Health (NIH) – awarded Heptares Therapeutics $5.5m (€4.9m) this week to aid development of a first-in-class Orexin-1 inhibitor to treat cocaine dependency and addiction.
“The Orexin-1 - also known as hypocretin - receptor regulates the substance seeking and reward pathways in the mid-brain that underlie addiction and craving” a spokesperson from the company told in-Pharmatechnologist.com.
“Pre-clinical experiments have demonstrated that blocking the Orexin-1 receptor using prototypical tool molecules, blocks drug seeking behaviours.”
The firm, a subsidiary of Japanese pharma company Sosei Group Corporation, will undertake the development of such a compound at its R&D facility in Welwyn Garden City, UK, and will use its proprietary GPCR structure-based drug discovery platform.
“Heptares’ tech has been used to stabilise the Orexin-1 receptor from which detailed info on the receptor binding site has been determined. Several Orexin-1 antagonists (blockers) have been discovered and will now be optimised to take forward into clinical trials.”
GPCRs are expressed in every type of cell in the body where their function is to transmit signals across the membrane, and, if targeted successfully by small molecule or biological inhibitor drugs, can address a range of diseases.
For example, GLP-1 (glucagon-like peptide-1) inhibitors have been approved as effective treatments in type 2 diabetes, and according to Heptares over a quarter of all drugs currently on the market target GPCR receptors.
Blocking the Orexin-1 receptor is a new approach to addiction, and while this grant focuses on treating cocaine addicts, such an inhibitor is also being tested to treat nicotine addiction and compulsive disorders like binge eating and gambling.