Navigation Links
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 treatment of Alzheimer's disease and other disorders involving cognitive impairment.

The Orexin-2 structure shows substantial topological differences compared to other peptide Family A receptors, and enables selective drug design to both Orexin-2 (chronic insomnia) and Orexin-1 (anti-craving in addiction and compulsive disorders) subtypes, and modelling of receptor activation.

The Heptares platform is nucleated around its unique ability, using its StaR® technology, to stabilise GPCRs in precisely defined, biologically-relevant conformations. These StaRs® can then be used, based on receptor structural information from X-ray crystallography and Biophysical Mapping™, to design and build (atom-by-atom) small molecules with specified drug action and properties, creating an unparalleled medicinal chemistry capability for addressing extremely difficult GPCR targets.

"No Family B GPCR trans-membrane domain structures have been solved until now, highlighting the power of our StaR® technology. This is a fundamental discovery for GPCR drug design, and for our understanding of the mechanism of action and function of these biologically important receptors," said Fiona Marshall, CSO of Heptares Therapeutics.

"These exciting new structural insights are allowing Heptares to deliver potentially ground-breaking new medicines, which is our sole focus. We have a robust platform and pipeline, with our industry-first selective Muscarinic M1 agonist expected to enter clinical development next year and further programmes for additional CNS and metabolic disorders advancing well," said Malcolm Weir, CEO of Heptares Therapeutics.

 

*Conference details

G-protein-coupled-receptors: from structural insights to functional mechanisms
12-14 September 2012
Monash University Prato Centre, Italy

4th RSC/SCI Symposium on GPCRs in Medicinal Chemistry
17-19 September 2012
Lilly UK, Erl Wood, Windlesham, Surrey, UK

About Heptares Therapeutics

Heptares discovers and develops new medicines targeting GPCRs (G protein-coupled receptors), a super-family of drug targets linked to a wide range of human diseases.  Our pharmaceutical partners include Shire, AstraZeneca, MedImmune and Takeda, and we have raised $40M from MVM Life Science Partners, Clarus Ventures, Novartis Venture Fund and Takeda Ventures.

Heptares is pioneering the application of structure-based drug design to the GPCR superfamily of targets and is focused on creating molecules that modulate high-value, yet historically undruggable or challenging, GPCRs.  Our platform incorporates proprietary technologies for engineering stabilised GPCRs in their natural pharmacological conformations, identifying previously unknown chemistries for GPCR protein-drug interactions, and deploying advanced fragment-based approaches to GPCR target space for the first time.

Using this approach, we have generated a broad pipeline of drug candidates for the treatment of serious disorders, including Alzheimer's disease, Parkinson's disease, schizophrenia, depression, chronic insomnia, addiction disorders, and diabetes.  For more information about Heptares, please visit http://www.heptares.com.


'/>"/>
SOURCE Heptares Therapeutics
Copyright©2012 PR Newswire.
All rights reserved

Related biology technology :

1. Heptares Grants Shire an Exclusive Worldwide Licence to Develop and Commercialise Novel Drug Candidate for CNS Disorders
2. Palatin Technologies, Inc. to Report Fiscal Year 2012 First Quarter Results; Teleconference and Webcast to be held on November 15, 2011
3. Avaxia Biologics, Inc. Raises $2.2 Million in First Closing of Series A Financing to Advance Oral Antibodies for Inflammatory Bowel Disease
4. Palatin Technologies, Inc. Reports First Quarter Fiscal Year 2012 Results; Teleconference and Webcast to be held on November 15, 2011
5. Fitzsimons Redevelopment Authority Rolls Out First Phase of Strategic Refocus With Appointment of Four Key Leaders in The Bioscience Industry to Its Board of Directors
6. Webcor Builders Selected as the General Contractor for First Phase of LA BioMeds New Campus Master Plan
7. China Cord Blood Corporation to Report Second Quarter and First Half of Fiscal 2012 Financial Results
8. Tiger Woods Gives Exclusive First Interview Since POWERED by FUSE Announcement!
9. The Pharmabiotic Research Institute (PRI) is Preparing to Publish its First Works on the Therapeutic and Medicinal Potential of Probiotics
10. Eye Surgery Center of Michigan First in Southeast Michigan to Perform Bladeless Cataract Surgery Using New LenSx® Laser Technology
11. Amgen Announces 2012 First Quarter Dividend
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/23/2017)... ... February 23, 2017 , ... The Greater Gift ... new partnership with Compass Research . GGI's mission is to advance global health ... a child in need in honor of each clinical trial volunteer. The vision of ...
(Date:2/23/2017)... ... February 22, 2017 , ... Seventy-one members ... named Fellows of the Society this year, the Fellows Committee has announced. The ... of optics, photonics, and imaging as well as their service to the Society ...
(Date:2/22/2017)... SAN DIEGO , Feb. 22, 2017  PrimeVax ... , will be presenting at the Annual Biocom Global ... on March 2, at 11:15 AM, at the Torrey ... are thankful to the organizers at Biocom who have ... this international symposium of biotechnology companies, investors, and clinical ...
(Date:2/22/2017)... ... February 22, 2017 , ... LabRoots , ... from around the world, is pleased to announce the 2nd annual Precision Medicine ... This premier, online-only conference focused on the development and advancements in precision medicine. ...
Breaking Biology Technology:
(Date:2/6/2017)... Feb. 6, 2017 According to Acuity ... driving border authorities to continue to embrace biometric ... are 2143 Automated Border Control (ABC) eGates and ... at more than 163 ports of entry across ... 2016 achieving a combined CAGR of 37%. APC ...
(Date:2/2/2017)... TOKYO , Feb. 1, 2017  Central ... innovative and meaningful advances worldwide, The Japan Prize ... Japan Prize, who have pushed the envelope in ... Information and Communication. Three scientists are being recognized ... outstanding achievements that not only contribute to the ...
(Date:1/26/2017)... 2017  Acuity Market Intelligence today released the ... Identity".  Acuity characterizes 2017 as a "breakout" year ... reflects a new understanding of the potential benefits ... digital identity are often perceived as threats to ... Principal of Acuity Market intelligence. "However, taken together ...
Breaking Biology News(10 mins):