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Heptares Solves First Family B GPCR Structure
Date:9/10/2012

WELWYN GARDEN CITY, England and BOSTON, September 10, 2012 /PRNewswire/ --

Update on novel structures and product pipeline to be presented at Biochemical Society and Royal Society of Chemistry meetings

 

Heptares Therapeutics today announces that it has used its StaR® technology to solve entirely in-house the first structure of a Family B sub-class G protein-coupled receptor (GPCR). Chief Scientific Officer, Fiona Marshall and Chief Executive Officer, Malcolm Weir, will present views of a high resolution X-ray crystal structure of the Corticotropin Releasing Factor (CRF-1) receptor, together with information about additional novel in-house GPCR structures and Heptares pipeline programmes, at upcoming scientific conferences.*

CRF-1, a drug target for depression and anxiety, is a member of the Family B sub-class of nearly 50 GPCRs, which includes many targets such as GLP-1 (diabetes), PTH (bone) and CGRP (migraine) that have proven intractable to small molecule chemistry. Novel and unexpected insights into receptor topology, conformation and compound binding have been revealed, showing major differences compared to the many already known Family A structures, such as beta-adrenergic receptor. Owing to the close relationship among Family B GPCRs, these insights from the CRF structure will allow high-quality structural models to be generated to the entire family and provide new avenues for discovery, which are being leveraged by the Company using its proprietary structure-based drug design platform.

Heptares is also reporting the first structure for the Muscarinic M1 receptor in the agonist conformation, and the first structure for the Orexin-2 receptor in an antagonist confirmation. The M1 structure shows conformational and subtype differences in the ligand binding site compared to muscarinic antagonist-bound structures, and is central to Heptares' selective orthosteric agonist programme for the treat
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SOURCE Heptares Therapeutics
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