GPR39: an orphan receptor begging for ligands

Drug Discov Today. 2023 Dec 18:103861. doi: 10.1016/j.drudis.2023.103861. Online ahead of print.ABSTRACTProgress in the understanding the receptor GPR39 is held up by inconsistent pharmacological data. First, the endogenous ligand(s) remain(s) contentious. Data pointing to zinc ions (Zn2+) and/or eicosanoids as endogenous ligands are a matter of debate. Second, there are uncertainties in the specificity of the widely used synthetic ligand (agonist) TC-G 1008. Third, activation of GPR39 has been often proposed as a novel treatment strategy, but new data also support that inhibition might be beneficial in certain disease contexts. Constitutive activity/promiscuous signaling suggests the need for antagonists/inverse agonists in addition to (biased) agonists. Here, we scrutinize data on the signaling and functions of GPR39 and critically assess factors that might have contributed to divergent outcomes and interpretations of investigations on this important receptor.PMID:38122967 | DOI:10.1016/j.drudis.2023.103861
Source: Drug Discovery Today - Category: Drugs & Pharmacology Authors: Source Type: research