Abstract 4712: GPCR panel establishment and application in drug discovery

Abstract G protein-coupled receptors (GPCRS) are the largest family of membrane proteins of cell surface receptors. It can be activated by various stimuli and play an important role in various physiological and pathological processes such as cell growth, proliferation, differentiation, metabolism, and homeostasis. Abnormal regulation of GPCR is associated with various human diseases, such as metabolic diseases, cardiovascular diseases, and eye diseases. G protein contains three subunits: α, β, and γ, which form a trimer. When extracellular ligands are bound to GPCRs which activate G protein and GTP phosphorylates Gα subunits, leading to the dissociation of Gα subunits from the trimer and dissociation from the β and γ subunits. In addition, Gα different subtypes of Gαs, Gαi and Gαq have different biological effects after activation, Gas-coupled receptors activate adenylyl cyclase (AC) to increase cAMP. In contrast, Gαi-coupled receptors activated adenylyl cyclase (AC) to inhibit cAMP. Gαq coupled receptors promote phospholipase C (PLC) to produce IP3, and IP3 can increase intracellular Ca2+ concentration. GPCR Panel With high general availability, which provides over 150 GPCR targets, covering wide families like 5-Hydroxytryptamine, adrenoceptors, Acetylcholine, dopamine, glucagon, and opioid receptors and having the selectivity of multiple species. It can conduct similar GPCR poly-link interaction and screening, used to study new GPCR drug development technology, detect the expression properties of GPCR receptors, reveal new GPCR structure and function, and screen GPCR drugs. We also constructed different assay platforms, including cAMP assay, Ca2+ flux assay, IP3 assay, β-arrestin recruitment assay and reporter assay to detect the different second messengers produced by G protein submits and GPCR-mediated multiple signaling pathways. This research constructed stable cell lines expressing GPCRs and provided related assays, which could be used to detect compounds' effects on GPCR targets successfully. In addition, the GPCR panel was applicable to both activating and inhibitory models, and the establishment of this platform provides a powerful tool for drug development of GPCR-related targets. Citation Format: Xiaoyan Wang, Ning Sui, Dandan Hu, Ziwei Zhang, Tiejun Bing. GPCR panel establishment and application in drug discovery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4712.