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Further validation of Heptares' StaRT technology
Heptares Therapeutics Ltd, the drug discovery company focused on the design and development of novel drugs based on G-protein-coupled receptors (GPCRs), notes that a new academic publication by the research group led by one of its scientific founders (Ref. 1) further validates the potential of its proprietary technology for creating purified, functional and stable G-protein receptors (GPCRs) for drug discovery and structural studies.
GPCRs play a crucial role in many diseases and are targets of 25-30% of all modern drugs, therefore they represent a major focus for pharmaceutical companies. However, they are notoriously difficult to isolate from cell membranes in an active form and this has severely hampered efforts to study GPCRs using traditional drug discovery techniques.
The paper, which was published in August in the international peer-reviewed journal Proceedings of the National Academy of Sciences by Chris Tate and other researchers at the Medical Research Council Laboratory for Molecular Biology (MRC LMB) in Cambridge, UK, describes a method for stabilizing the adenosine A2a receptor in an active form outside the cell membrane. The A2a receptor is important for regulating blood flow, immune responses and the activity of neurones in the brain. It is the target for drugs to treat diseases such as asthma and Parkinson's disease.
The research team found that the adenosine A2a receptor could be stabilised in both agonist-bound and antagonist-bound conformations by inducing different point mutations in its structure. By combining certain mutations, the stability of the receptor can be increased even further while preserving its functional and drug-binding characteristics. This technique forms the basis of Heptares's core proprietary StaRT technology (Stabilised Receptor) and enables Heptares to apply drug discovery approaches such as molecular modeling, solution phase assays, coupling to surfaces (chips), crystallisation and structure-based design to the StaRs it generates.
Heptares' CEO, Dr Malcolm Weir, said: "This is the second published report of a GPCR drug target on which our StaR technology has been successfully applied in recent months, the first being the ß1 adrenergic receptor, which was the subject of a paper published in Nature in June this year (Ref. 2). This new publication further validates our unique technology and highlights its transferability across the GPCR target family.. Our congratulations go to Chris Tate and his research team in Cambridge."
References
1. Magnani, F. et al (2008) Proc. Natl. Acad. Sci. 105 (31), 10744-10749
2. Warne, T. et al (2008) Nature 454 (7203), 486-91
Notes to Editors
About GPCRs
There are nearly 800 known GPCRs and they belong to the largest family of membrane proteins in the human genome. Their function is to sense molecules outside the cell, hence 'receptors', and trigger cellular reactions. GPCRs have seven membrane-spanning domains and are essential for the body to complete a wide range of physiological responses. They allow us to process light and smells, regulate our behaviour, mood and immune response. They are essential in autonomic nervous system transmission. They also control blood pressure, heart rate and digestive processes. This means GPCRs play a crucial role in many diseases and are targets of 25-30% of all modern drugs, and therefore represent a major focus for pharmaceutical companies.
About Heptares Therapeutics Ltd
Heptares is a GPCR-focused drug discovery company deploying its proprietary StaRT technology principally in the Central Nervous System (CNS) and metabolic disease areas. GPCRs are the single most important family of drug targets in the human body, but because of their inherent instability they are intractable to structural studies and in vitro screening. StaRT technology enables the engineering of stabilised GPCRs, making them amenable to these vital drug discovery approaches. There are many clinically relevant GPCR targets across a wide range of therapeutic areas where discovery is advancing slowly and for which structural information, novel screening approaches and potential antibody therapeutics would greatly enhance progress.
StaRT technology arose out of the pioneering work of Heptares' founding scientists, Richard Henderson and Chris Tate at the MRC Laboratory of Molecular Biology, Cambridge, and of a wider group of MRC scientists, including Gebhard Schertler, and Ed Hulme of the National Institute for Medical Research, London. Heptares is managed by Malcolm Weir (Chief Executive Officer) and Fiona Marshall (Chief Scientific Officer) with John Berriman as Chairman, and is based in London. For more information, see www.heptares.com
Contact Information:
Heptares Therapeutics Ltd
Dr Malcolm Weir,
1-3 Burtonhole Lane,
Mill Hill,
London NW7 1AD
U.K.
E-mail: malcolm.weir@heptares.com
Phone: +44 (0)20 8906 7182
Mobile: +44 (0)7968 947268
Fax: +44 (0)20 8906 7200
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