G protein-coupled receptor (GPCR) is a complete membrane protein, which is used by cells to convert extracellular signals into intracellular reactions. This includes the response to hormones and neurotransmitters, as well as the response to visual, olfactory, and taste signals. Specifically, GPCR is the largest membrane protein family, which mediates the response of most cells to hormones and neurotransmitters. Besides, GPCR is almost relevant to the whole physiological function and pathological process. Moreover, GPCR has a unique combination of signal transduction activities. Furthermore, GPCRs are related to the pathogenesis of Alzheimer disease (AD) and multiple stages of the hydrolysis process of amyloid precursor protein (APP). APP is a precursor protein relevant to the formation of amyloid plaques in the brain of AD patients. The ability of GPCR to transmit signals through the cell membrane depends on its ability to change shape.

Meanwhile, many GPCRs can continue to activate G proteins from intracellular compartments after internalization. The G protein-coupled receptor (GPCR) responds to a variety of ligands and mediates the response of cells to hormones and neurotransmitters, as well as olfaction and taste. Nonetheless, the adenosine receptor (AR) is a family of G protein-coupled receptors. The adenosine receptor is the main target of caffeine. They may also become promising therapeutic targets for a variety of diseases, including cerebral and cardiac ischemic diseases, sleep disorders, immune and inflammatory disorders, and cancer. Importantly, AR contains a group of GPCR, which can mediate the physiological effects of adenosine. Now, we will introduce an allosteric modulator of GPCRs and AR, SCH-202676.

SCH-202676 is a GPCRs and AR Allosteric Modulator

In the first place, SCH-202676 is an allosteric modulator of GPCRs and AR. Particularly, SCH-202676 has antiviral activity and inhibits 3CL^pro in a time-dependent manner with an IC₅₀ value of 0.655 µM.

In the next place, SCH-202676 with 0.01-10 µM for 0-20 min shows antiviral activity. SCH-202676 inhibits 3CL^pro in a time-dependent manner, with IC₅₀ values of 0.409, 0.302, 0.206 and 0.191 µM for 0, 5, 10 and 20 min, respectively. Obviously, SCH-202676 enhances the labeling of [³⁵S]GTPγS in rat forebrain membranes. SCH-202676 inhibits the agonist [³H]UK-14,304 and the antagonist [³H] Yohimbine binding to the α_2a adrenergic receptor.

Last but not least, SCH-202676 with 10 μM selectively accelerates agonist dissociation at adenosine A3 receptors. Additionally, SCH-202676 slows antagonist dissociation at adenosine Ai receptors or accelerates antagonist dissociation at adenosine AzA receptors.

All in all, SCH-202676 is an allosteric modulator of G protein-coupled receptors (GPCRs) and AR.

References:

[1]  Ren P, et al. Eur J Med Chem. 2023 Jan 18;249:115129.

[2]  Lewandowicz AM, et al. Br J Pharmacol. 2006 Feb;147(4):422-9.