What are GPCRs

 

GPCRs are a super-family of integral cell membrane proteins that are present on cells and tissues throughout the body. GPCRs are involved in signalling pathways that influence a wide range of biological processes and are important drug targets implicated in many human diseases and disorders.

GPCRs are targeted by approximately 34% of currently marketed drugs, which account for around 27% of the global market share of pharmaceutical sales. GPCRs form the largest human membrane protein family, with around 400 receptors*, of which approximately 224 remain yet to be explored, offering broad untapped potential.

*Non-olfactory

The Problem

Despite GPCRs representing one of the most important groups of drug targets for modern medicine, drug design specifically targeting GPCRs, rather than traditional random compound-screening approaches, remains challenging. Historically, mapping the structure of GPCRs when they are isolated from the cell membrane has been difficult as GPCRs are unstable in isolation, often preventing structure determination.

Our Solution

Our proprietary StaR® / SBDD platform can overcome these hurdles and address this major opportunity for the generation of small molecules, peptides and therapeutic antibodies targeting challenging or previously undruggable GPCRs.

Our technology enables us to discover and design very selective, high-affinity drug candidates. StaR® is currently the only technology that can remove the GPCR structure from the cell membrane while retaining its original three-dimensional integrity and enabling co-structure determination with multiple small molecules, including those with low affinity.

We have succeeded in generating the world’s first X-ray crystal structures of more than 15 receptors, and have also succeeded in elucidating over 200 structures for these receptors bound to drug molecules, a vital step in a viable SBDD process. Many members of the GPCR family have been difficult to drug with molecules discovered using other technologies, but our technologies enable the design of drug candidates that have not previously existed.

We believe that our approach will improve the chances of designing safer and more selective drugs targeting GPCRs, overcoming low selectivity and poor pharmacokinetic profiles or toxicity, often present in existing compounds identified by other means. Our approach has led to the generation of highly differentiated candidates to multiple challenging or intractable targets, as had been widely documented in scientific literature.

Structure of GPCR thermostabilized in the agonist conformation and in complex with endogenous agonist ligand (grey)



Our unique and powerful platform capability enables determination of 3D structures of GPCRs and complexes with bound ligands by X-ray crystallography, Cryo-EM and Biophysical Mapping™