mProX™ Human GPR6 Stable Cell Line

Lu Y, et al. "Molecular insights into orphan G protein-coupled receptors relevant to ." British journal of pharmacology, 2023.
This article explores the relationship between GPR3, GPR6, GPR12, GPR52, GPR85, GPR88, and GPR139 and schizophrenia. The authors review the expression, signalling mechanisms, and cellular function of these receptors along with the development of small molecule treatments and structural insights. They aim to present a concise overview of the increasing evidence and potential for new categories of treatments for schizophrenia.
Pubmed: 37605621   DOI: 10.1111/bph.16221

Gay EA, et al. "The development of diphenyleneiodonium analogs as GPR3 agonists.." Bioorganic & medicinal chemistry letters, 2023.
G protein-coupled receptor 3 (GPR3) is an orphan receptor that may play a role in numerous physiological processes, including drug abuse, neuropathic pain, and anxiety and depression-related disorders. The exploration of GPR3 through pharmacological studies has been hindered by a limited number of known agonists and inverse agonists for this constitutively active receptor. This study in medicinal chemistry aims to address this by identifying GPR3 agonists from the diphenyleneiodonium (DPI) scaffold. The most potent full agonist discovered was the 3-trifluoromethoxy analog (32), with an EC(50) of 260 nM and 90% efficacy compared to DPI. Through investigation of a homology model of GPR3, a binding site rich in potential pi-pi and pi-cation interactions crucial for stabilizing DPI-scaffold agonists was identified. MMGBSA free energy analysis demonstrated a strong correlation with trends in observed EC(50)s. The DPI analog series also maintained a high selectivity for GPR3 over GPR6 and GPR12, as observed with DPI. Despite achieving significant improvements in potency with the scaffold, attempts to modify the iodonium ion and enhance the scaffold's drug-like properties were unsuccessful.
Pubmed: 37541631   DOI: 10.1016/j.bmcl.2023.129427