GPCR, also known as G Protein-Coupled Receptors, is the largest membrane protein family in the human body and the largest drug target protein family, involved in diseases primarily including neurological disorders, cardiovascular diseases, cancer, and inflammation.
GPCR receptors play a crucial role in many physiological and pathological processes by perceiving external stimuli, transmitting extracellular information into cells, and ultimately leading to subsequent cellular responses, essential for maintaining human body functions. These regulatory processes are achieved through coordination between ligands, GPCR, effector proteins, and downstream signaling pathways. Upon ligand binding, GPCR undergoes conformational changes, leading to the recruitment and activation of specific effector proteins, triggering the regulation of downstream signaling pathways.
Compared to small molecules, GPCR antibodies have unique advantages such as lower in vivo clearance rates, longer duration of action, and lower dosing frequency; antibodies exhibit significantly greater selectivity than small molecules. Additionally, due to the blood-brain barrier, antibody drugs cannot enter the central nervous system. Therefore, for GPCRs expressed in both peripheral and central nervous systems, therapeutic antibodies can be developed to target only the peripheral regions, reducing potential toxic side effects on the central nervous system.
However, due to the low expression levels of GPCR proteins on the cell surface, limited extracellular exposure, complex folding conformations, and relative difficulties in purification, the development of large molecular biopharmaceuticals targeting GPCRs has always been challenging.
