In:
Frontiers in Endocrinology, Frontiers Media SA, Vol. 14 ( 2023-6-26)
Abstract:
G protein-coupled receptors (GPCRs) represent the target for approximately a third of FDA-approved small molecule drugs. The adenosine A 1 receptor (A 1 R), one of four adenosine GPCR subtypes, has important (patho)physiological roles in humans. A 1 R has well-established roles in the regulation of the cardiovascular and nervous systems, where it has been identified as a potential therapeutic target for a number of conditions, including cardiac ischemia-reperfusion injury, cognition, epilepsy, and neuropathic pain. A 1 R small molecule drugs, typically orthosteric ligands, have undergone clinical trials. To date, none have progressed into the clinic, predominantly due to dose-limiting unwanted effects. The development of A 1 R allosteric modulators that target a topographically distinct binding site represent a promising approach to overcome current limitations. Pharmacological parameters of allosteric ligands, including affinity, efficacy and cooperativity, can be optimized to regulate A 1 R activity with high subtype, spatial and temporal selectivity. This review aims to offer insights into the A 1 R as a potential therapeutic target and highlight recent advances in the structural understanding of A 1 R allosteric modulation.
Type of Medium:
Online Resource
ISSN:
1664-2392
DOI:
10.3389/fendo.2023.1184360
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2023
detail.hit.zdb_id:
2592084-4
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