Journal ArticleDOI
Emerging paradigms in GPCR allostery: implications for drug discovery
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TLDR
New findings have the potential to alter how screening for allosteric drugs is performed and may increase the chances of success in the development ofallosteric modulators as clinical lead compounds.Abstract:
Allosteric ligands bind to G protein-coupled receptors (GPCRs; also known as seven-transmembrane receptors) at sites that are distinct from the sites to which endogenous ligands bind. The existence of allosteric ligands has enriched the ways in which the functions of GPCRs can be manipulated for potential therapeutic benefit, yet the complexity of their actions provides both challenges and opportunities for drug screening and development. Converging avenues of research in areas such as biased signalling by allosteric ligands and the mechanisms by which allosteric ligands modulate the effects of diverse endogenous ligands have provided new insights into how interactions between allosteric ligands and GPCRs could be exploited for drug discovery. These new findings have the potential to alter how screening for allosteric drugs is performed and may increase the chances of success in the development of allosteric modulators as clinical lead compounds.read more
Citations
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In Vitro Characterization of 6-Methyl-3-(2-nitro-1-(thiophen-2-yl)ethyl)-2-phenyl-1H-indole (ZCZ011) at the Type 1 Cannabinoid Receptor: Allosteric Agonist or Allosteric Modulator?
TL;DR: In this paper , the in vitro activity of the positive allosteric modulator ZCZ011, explicitly considering its effects on receptor regulation, was systematically characterized with real-time BRET approaches for G protein dissociation, cAMP signaling and β-arrestin translocation.
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Chapter 74 – Caffeine, Adenosine A1 Receptors, and Brain Cortex. Molecular Aspects
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References
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Journal ArticleDOI
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Journal ArticleDOI
The Many Roles of Chemokines and Chemokine Receptors in Inflammation
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TL;DR: Five independent crystal structures of CXCR4 bound to an antagonist small molecule IT1t and a cyclic peptide CVX15 at 2.5 to 3.2 angstrom resolution reveal a consistent homodimer with an interface including helices V and VI that may be involved in regulating signaling.
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