Use of the X-ray structure of the β2-adrenergic receptor for drug discovery. Part 2: Identification of active compounds

The recently published X-ray structures of the β2-adrenergic receptor are the first examples of ligand-mediated GPCR crystal structures. We have previously performed computational studies that examine the potential viability of these structures for use in drug design, exploiting known ligand activities. Our previous study and a newly reported β2/Timolol X-ray complex provide validation of the computational approaches. In the present work, we use the X-ray structures to extract, via in silico high-throughput docking, compounds from proprietary and commercial databases and demonstrate the successful identification of active compounds by radioligand binding.

Graphical abstractThe previous use of a β2-adrenergic receptor’s X-ray in docking studies is now validated with binding data and a recently published X-ray structure with Timolol.Figure optionsDownload full-size imageDownload as PowerPoint slide