Welwyn Garden City, UK. 29 June 2011 – Heptares Therapeutics has published an overview of Biophysical Mapping™ and its application to G-protein coupled receptor (GPCR) drug targets in the Journal of Medicinal Chemistry (Ref. 1). Biophysical Mapping™ is a new technology, invented by scientists at Heptares, for elucidating and characterizing the interactions between GPCRs and small molecule ligands that bind to these receptors. Biophysical Mapping™ is one of several advanced drug discovery approaches created and implemented by Heptares, a technology pioneer in GPCR drug discovery.

Building upon Heptares’ transformational technology for generating stabilised GPCRs, or StaRs®, Biophysical Mapping™ works by measuring the strength and rate of binding of arrays of small molecules to many StaR® variants immobilised on biosensor chips. The wealth of information collected via Biophysical Mapping™ can then be used to produce high-quality three-dimensional pictures of ligands binding to various sites on GPCRs and to facilitate structure-based design of new and superior drug compounds targeting these proteins.

“Biophysical Mapping™ was specifically designed to augment classical analytical methods such as x-ray crystallography by providing direct insight into the energetic and kinetic elements of specific interactions between receptors and their ligands, information not provided by crystallography,” said Malcolm Weir, CEO of Heptares. “In addition, Biophysical Mapping™ rapidly offers high quality structural biology information, which combined with power of our revolutionary StaR® technology, enables GPCR drug discovery campaigns to be significantly accelerated.”

GPCRs are a super-family of drug targets linked to a broad range of diseases. Historically, the rational design of GPCR-targeted drugs has significantly lagged behind the rational design of drugs aimed at other target families. Heptares scientists have recently reviewed the progress in GPCR drug discovery and the growing potential of using structure-based drug discovery approaches (Ref. 2).

A key obstacle to progress in GPCR drug discovery has been the instability of GPCRs when removed from their natural locations on the surface of cells, which has made it difficult or impossible to determine the structure of many GPCR targets and to design novel small molecules optimised to bind to these targets. Heptares has overcome this obstacle by stabilising the natural GPCR into a StaR® form, enabling the GPCR’s structure to be determined using both novel techniques like Biophysical Mapping™ and classical methods such as x-ray crystallography.

References

1)     Biophysical Mapping of Adenosine A_2A Receptor (Article). A. Zhukov et al. (2011) J. Med. Chem. DOI: 10.1021/jm2003798

2)     Progress in Structure Based Drug Design for G Protein-Coupled Receptors (Perspective). M. Congreve et al. (2011) J. Med. Chem. DOI: 10.1021/jm200371q