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Biased ligand modulation of seven transmembrane receptors (7TMRs): functional implications for drug discovery.

Abstract：

:Seven transmembrane receptors (7TMRs), also known as G-protein-coupled receptors (GPCRs), have proven to be valuable targets for the development of therapeutics. The expansion of our understanding of 7TMR downstream signaling pathways beyond G-proteins has broadened our appreciation of the versatility of these cell surface receptors. In particular, the increased awareness of 7TMR engagement of β-arrestin signaling has opened up additional avenues for drug discovery. 7TMRs can adopt different conformations and in response to various ligands can lead to a bias in downstream signaling mechanisms when comparing the overall efficacy between G-protein and β-arrestin dependent pathways. In 2012, we organized a session at the Spring National Meeting of the American Chemical Society on biased signaling in 7TMRs.1-4 Building on that experience, we provide in this Miniperspective some examples that exemplify developments in the area of biased 7TMR signaling and highlight some cautionary notes as well as some of the exciting opportunities for drug discovery.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Correll CC,McKittrick BA

doi

10.1021/jm401677g

subject

Has Abstract

pub_date

2014-08-28 00:00:00

pages

6887-96

issue

16

eissn

0022-2623

issn

1520-4804

journal_volume

57

pub_type

杂志文章

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