Addex Scientists Discover and Characterize the First Potent and Selective Small Molecule Negative Allosteric Modulator Targeting mGlu7 receptor
Geneva, Switzerland, 20 December 2012 – (SIX: ADXN), 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). (Kalinichev et al, 2012, JPET fast forward online publication December 21, 2012).
“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 of CHF700,000 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.
Addex Therapeutics (www.addextherapeutics.com) discovers and develops an emerging class of small molecule drugs, called allosteric modulators, which have the potential to be more specific and confer significant therapeutic advantages over conventional "orthosteric" small molecule or biological drugs. The Company uses its proprietary discovery platform to address receptors and other proteins that are recognized as attractive targets for modulation of important diseases with unmet medical needs. The Company's two lead products are being investigated in Phase 2 clinical testing: dipraglurant (ADX48621, an mGlu5 negative allosteric modulator or NAM) is being developed by Addex to treat Parkinson's disease levodopa-induced dyskinesia (PD-LID); and ADX71149 (mGlu2 positive allosteric modulator or PAM) is being developed in collaboration with Janssen Pharmaceuticals Inc. to treat schizophrenia and anxiety seen in patients suffering from major depressive disorder. Addex also is advancing several preclinical programs including: GABA-BR PAM for spasticity in MS, OAB and other disorders; mGlu4 PAM for Parkinson's, MS, anxiety and other diseases. In addition, Addex is applying its proprietary discovery platform to identify highly selective and potent allosteric modulators of a number of both GPCR and non-GPCR targets that are implicated in diseases of significant unmet medical need.
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Disclaimer: The foregoing release may contain forward-looking statements that can be identified by terminology such as "not approvable", "continue", "believes", "believe", "will", "remained open to exploring", "would", "could", or similar expressions, or by express or implied discussions regarding Addex Therapeutics, formerly known as, Addex Pharmaceuticals, its business, the potential approval of its products by regulatory authorities, or regarding potential future revenues from such products. Such forward-looking statements reflect the current views of Addex Therapeutics regarding future events, future economic performance or prospects, and, by their very nature, involve inherent risks and uncertainties, both general and specific, whether known or unknown, and/or any other factor that may materially differ from the plans, objectives, expectations, estimates and intentions expressed or implied in such forward-looking statements. Such may in particular cause actual results with allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-BR or other therapeutic targets to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-BR or other therapeutics targets will be approved for sale in any market or by any regulatory authority. Nor can there be any guarantee that allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-BR or other therapeutic targets will achieve any particular levels of revenue (if any) in the future. In particular, management's expectations regarding allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-BR or other therapeutic targets could be affected by, among other things, unexpected actions by our partners, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; competition in general; government, industry and general public pricing pressures; the company's ability to obtain or maintain patent or other proprietary intellectual property protection. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Addex Therapeutics is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise, except as may be required by applicable laws.