G Protein-Coupled Receptors: Chemical and Structural Insights for Drug Discovery

Nagy, Manar; Kishk, Safaa; Darwish, Khaled Mohamed; Mostafa, Samia; Salama, Ismail

doi:10.21608/rpbs.2025.376428.1369

G Protein-Coupled Receptors: Chemical and Structural Insights for Drug Discovery

Document Type : Mini-reviews

Authors

¹ Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Suez Canal University

² Pharmaceutical Medicinal Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt

10.21608/rpbs.2025.376428.1369

Abstract

G-protein coupled receptors (GPCRs) are very popular as integral membrane protein receptors which are used by cells to transfer the extracellular signals into intracellular responses. GPCRs form a superfamily which subdivided into 5 families [Glutamate (G), Rhodopsin (R), Adhesion (A), Frizzled/Taste2 (F), Secretin (S)] based on their phylogenetic tree. All subfamilies of GPCRs are made up of seven trans membrane proteins with three extracellular and three intracellular domains. Adenosine receptors are type of GPCRs. They are divided into four types of receptors (A1R, A2AR, A2BR and A3R). The accumulated extracellular adenosine mediates its regulatory functions by binding to one of four adenosine receptors. Adenosine emerges as a promising target for cancer therapy. It mediates protumor activities by inducing tumor cell proliferation, angiogenesis, chemo resistance, and migration/invasion by tumor cells. It also inhibits the functions of immune cells. In recent years, targeting one or more components of the adenosinergic pathway could be promising treatment strategies for individual cancer patients. The increasing evidence suggests that A2AR and A3R could be used as novel therapeutic targets for manipulating the antitumor immunity suppression.

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