GPCR, known as G protein-coupled receptor in Chinese, is the largest membrane protein family in the human body and the largest drug-targeting protein family, mainly involved in diseases such as neurological disorders, cardiovascular diseases, cancer, and inflammation.
GPCR receptors play a crucial role in many physiological and pathological regulations by sensing external stimuli, transmitting extracellular information into cells, and ultimately leading to subsequent cellular responses. These regulations 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, thus triggering the modulation of downstream signaling pathways.
Compared to small molecules, GPCR antibodies have unique advantages such as lower clearance rates in the body, longer duration of action, and lower dosing frequency. Antibodies also exhibit significantly better selectivity than small molecules. Additionally, due to the blood-brain barrier, antibody drugs cannot penetrate 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 the toxic side effects on the central nervous system.
However, due to the low expression levels of GPCR proteins on the cell surface, limited extracellular domains, complex folding conformations, and challenges in purification, traditional methods for developing large molecule biopharmaceuticals targeting GPCRs have been quite difficult.
