Product News: Addex Scientists Identify and Characterize the First Potent and Selective Small Molecule Negative Allosteric Modulator Targeting mGlu7 Receptor

20 Dec 2012

The discovery and characterization of a potent and selective small molecule negative allosteric modulator is a significant breakthrough in the validation of this GPCR target for the potential treatment of major neurological indications such as PTSD and OCD.

Addex Therapeutics Ltd, a leading company pioneering allosteric modulation-based drug discovery and development, announced today the publication of new scientific findings in the Journal of Pharmacology and Experimental Therapeutics, describing the discovery and characterization of ADX71743, a novel, potent and selective negative allosteric modulator (NAM) of the metabotropic glutamate receptor 7 (mGlu7).

"The discovery and characterization of ADX71743 offers an important and much needed new approach to understanding the role of mGlu7 in the underlying pathophysiology of psychiatric and neurologic disorders" said Professor Peter Flor, one of the scientists who identified the mGlu7 receptor and a pioneer in the field of mGlu7 pharmacology.

mGlu7 is one of the most expressed receptors within the family of eight mGlu receptors, and is thought to play a central role in multiple CNS functions, such as emotional and stress reactivity, learning, memory and attention. mGlu7 is considered a promising novel target for potential treatment of a variety of disorders, including post-traumatic stress disorder (PTSD), obsessive compulsive disorder (OCD), anxiety, depression, drug abuse and schizophrenia. Understanding the role of the mGlu7 receptor has been hampered by the lack of selective, bioavailable and brain-penetrant pharmacological agents. This publication describes the full characterization of ADX71743, a novel potent and selective mGlu7 NAM, in both in vitro and in vivo studies. The compound was active in rodent models of anxiety and of OCD. Novel chemical series of mGlu7 NAMs are currently being optimized to identify one or several compounds that Addex plans to advance into development.

Commenting on the data, Dr Robert Lütjens, Vice-President of Biology and co-author of the publication explained that "the identification of mGlu7 NAM combined with our success in identifying mGlu7 positive allosteric modulators (PAM) provides us with a powerful advantage in elucidating the importance of mGlu7 in disease processes and the development of potential new differentiated therapeutics."

"This is yet another validation and demonstrates the power of our innovative allosteric modulator drug discovery platform to identify novel small molecule allosteric modulators of a receptor that was difficult to address using conventional small molecule approaches," commented Graham Dixon, CSO at Addex.

Addex recently announced being awarded a grant from the Swiss Commission for Technology and Innovation (CTI) to develop allosteric modulator therapeutics for neurodegenerative and psychiatric diseases including further characterization of allosteric modulators against mGlu4 and mGlu7.