Narrowing the GPCR space

For some time, GPCRs have been considered relatively easy drug targets. But despite success as a class, only a fraction of the total number of GPCRs is being therapeutically exploited. This is because GPCRs, sometimes referred to as seven transmembrane (7TM) receptors, are generally very difficult to produce in sufficient amounts and quality for crystallization and X-ray structure determination, when compared with soluble proteins.

Conventional drug discovery on GPCRs has been based on design from endogenous ligands, serendipitous findings, or via high throughput screening. However, even HTS with GPCRs is not a trivial exercise. It requires large investments in chemical libraries, the development of robust assays, and substantial post-HTS work to sort out genuine hits from false positives. ...