March 18, 2013
Scientific paper published in Molecular Pharmacology
Heptares Therapeutics, the leading GPCR drug discovery and development company, announces the publication of a new paper describing how 'reverse pharmacology', enabled by its StaR® technology, can be applied to and accelerate GPCR-based drug discovery. The paper has been published in
(ref. 1) and is available online by clicking
The authors from Heptares describe for the first time how StaR technology enables the study of isolated GPCRs locked in conformations that correspond to agonist or antagonist pharmacology, and the elucidation of their respective 3D structures.
These StaRs and structures can be used to select and design compounds with specific pharmacologies, such as inverse agonist, partial agonist or full agonist, based on their ability to bind differentially to the agonist and antagonist StaRs. For example a full agonist will preferentially bind to the agonist StaR.
This approach is termed 'reverse pharmacology' since classically compounds are made and tested in cells and tissues, and only then can their preferred receptor conformation and activity be determined, a process subject to variation depending on the assay system and lacking precision.
"The ability to predict whether a compound will behave as an agonist, inverse agonist or antagonist in an
setting is a very powerful tool for drug discovery," said
, Heptares' Chief Scientific Officer. "Combining this approach with our unique StaR technology is enabling Heptares to advance our pipeline of novel compounds targeting important GPCR targets, and those of our partners, towards the clinic."
- Bennett, K.A. et al. Pharmacology and Structure of Isolated Adenosine A2A Receptor Define Ligand Efficacy, 2013, Mol. Pharmacol. doi:10.1124/mol.112.084509
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