Discussion

Despite significant effort spanning many decades traditional screening approaches such as high-throughput screening have failed to fully unlock the potential of the GPCR superfamily and new, complementary approaches to GPCR drug discovery are required.
Heptares have tackled this challenge developing an integrated drug discovery platform around a unique ability, using stabilised receptor (StaR®) technology, to stabilise receptors in precisely defined biologically-relevant conformations. StaRs® are amenable to a number of techniques that cannot be readily used with wild-type GPCRs, including biophysical and biochemical fragment screening, kinetic profiling using surface-plasmon resonance (SPR), crystallographic studies and Biophysical Mapping. Structure-based drug discovery is now a reality for this family, and the impact of new structures for GPCR drug discovery will be discussed.