论文信息 - To Bind or Not to Bind: Unravelling GPCR Polypharmacology

To Bind or Not to Bind: Unravelling GPCR Polypharmacology

Interaction of a single drug with multiple targets through "polypharmacology" is increasingly recognized as necessary for treatment of complex diseases, such as schizophrenia. G protein-coupled receptors (GPCRs) are major medicinal targets, and understanding the structural basis of both GPCR drug selectivity and promiscuity could provide novel avenues for drug development.

Arthur Christopoulos | Patrick M. Sexton | P. Sexton | A. Christopoulos

[1] J. Wess,et al. M1 muscarinic allosteric modulators slow prion neurodegeneration and restore memory loss , 2016, The Journal of clinical investigation.

[2] R. Abagyan,et al. RETRACTED ARTICLE: Orphan receptor ligand discovery by pickpocketing pharmacological neighbors , 2016, Nature Chemical Biology.

[3] M. Babu,et al. Molecular signatures of G-protein-coupled receptors , 2013, Nature.

[4] Nicholas W. Frankel,et al. Building a Stable Relationship: Ensuring Homeostasis among Cell Types within a Tissue , 2018, Cell.

[5] Angela D. Wilkins,et al. Evolutionary action and structural basis of the allosteric switch controlling β2AR functional selectivity , 2017, Nature Communications.

[6] David E. Gloriam,et al. 5-HT2C Receptor Structures Reveal the Structural Basis of GPCR Polypharmacology , 2018, Cell.

[7] B. Roth,et al. Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia , 2004, Nature Reviews Drug Discovery.

[8] L. Bohn,et al. Bias Factor and Therapeutic Window Correlate to Predict Safer Opioid Analgesics , 2017, Cell.

[9] Bryan L Roth,et al. Discovery of new GPCR ligands to illuminate new biology. , 2017, Nature chemical biology.

[10] Chris de Graaf,et al. A Molecular Pharmacologist’s Guide to G Protein–Coupled Receptor Crystallography , 2015, Molecular Pharmacology.