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:3/28/2017)... , ... March 28, 2017 , ... ... Phase II Small Business Innovation Research (SBIR) grant from the National Science Foundation ... over two years to develop a suite of BioGel™ biopolymer materials for hygiene ...
(Date:3/28/2017)... Summary This report provides all ... its partnering interests and activities since 2010. Description The ... insight into the partnering activity of one of the world,s ... are prepared upon purchase to ensure inclusion of the most ... report will be delivered in PDF format within 1 working ...
(Date:3/28/2017)... Belgium , March 28, 2017 ... (NYSE MKT: VNRX), today announced the engagement of Deborah ... LLC, as a strategic consultant. Dr. Vollmer Dahlke,s ... securing non-dilutive funding in the State of Texas ... . Dr. Vollmer Dahlke has significant experience ...
(Date:3/28/2017)... , March 28, 2017  Viking Therapeutics, Inc. ... the development of novel therapies for metabolic and endocrine ... Brian Lian , Ph.D., will deliver a corporate presentation ... NASH Investor Conference, being held April 3, 2017 at ... Details for this presentation are as follows: ...
Breaking Biology Technology:
(Date:3/20/2017)... At this year,s CeBIT Chancellor Dr. Angela Merkel ... came to the DERMALOG stand together with the Japanese Prime Minster Shinzo ... At the largest German biometrics company the two government leaders could see ... as well as DERMALOG´s multi-biometrics system.   Continue ... ...
(Date:3/13/2017)... Future of security: Biometric Face Matching software  ... ... DERMALOGs Face Matching enables to match face pictures against each other or against ... (PRNewsFoto/Dermalog Identification Systems) ... Matching" is the fastest software for biometric Face Matching on the market. The ...
(Date:3/7/2017)... Brandwatch , the leading social intelligence company, today announces that ... uncover insights to support its reporting, help direct future campaigns, and ... youth charity will be using Brandwatch Analytics social listening and analytics ... of the topics and issues that are a priority for its ... "Until recently ...
Breaking Biology News(10 mins):