Impact of GPCR Structures on Drug Discovery.

By M. Congreve, Chris de Graaf, N. Swain, C. Tate. 2020

296 citations recorded by the source corpus.

Structures of 70 unique G protein-coupled receptors (GPCRs) have been determined, with over 370 structures in total bound to different ligands and the receptors in various conformational states. Structure-based drug design has been applied to an increasing number of GPCR targets over the past decade and now a few of these drug candidates have entered clinical trials. Given the length of time required for a drug to reach the market, there are no documented examples of licensed drugs being developed with the aid of a structure, but this is likely to change as current efforts come to fruition.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology, Radiology, Nuclear Medicine and Imaging

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. Michael Feig
2. Lim Heo
3. Jens Meiler
4. Vsevolod Katritch

In Molecular Biology

1. Lim Heo
2. Michael Feig
3. Jens Meiler
4. Davide Sala
5. Peter W. Hildebrand
6. Anastasiia V. Sadybekov
7. Vsevolod Katritch
8. David Baker

In Radiology, Nuclear Medicine and Imaging

1. Jens Meiler
2. Peter W. Hildebrand
3. Davide Sala
4. Lim Heo
5. Michael Feig

Citations in the corpus

• Multi-State Modeling of G-protein Coupled Receptors at Experimental Accuracy (2021, background): “The number of experimental GPCR structures has steadily increased since.(2) As of July 29, 2021, 574 GPCR structures have been deposited to the protein data bank (PDB).”
• Computational approaches streamlining drug discovery (2023, background): “In silico screening by docking molecules of the virtual library into a receptor structure and predicting its ‘binding score’ is a well-established approach to hit and lead discovery and had a key role in recent drug discovery success stories 11,17,51 .”
• Biasing AlphaFold2 to predict GPCRs and kinases with user-defined functional or structural properties (2022, background): “For structure-based drug discovery and design, having at least one high-accuracy structure is essential (Congreve et al., 2020).”