Technical Articles

The glucose-dependent insulinotropic polypeptide receptor (GIPR) is a key member of the class B1 G protein-coupled receptor family, forming a core receptor network with GLP-1R and GCGR to regulate glucose homeostasis and energy metabolism.

The glucagon-like peptide-1 receptor (GLP-1R) is an important member of the class B1 G protein-coupled receptor (GPCR) family and plays a key role in glucose homeostasis regulation. Since the first GLP-1 receptor agonist (GLP-1RA), exenatide, was approved for the treatment of type 2 diabetes in 2005, this target has become one of the most successful targets in the development of drugs for metabolic diseases.

The glucagon receptor (GCGR) is a crucial member of the class B G protein-coupled receptor family, forming a core receptor network with GLP-1R and GIPR to regulate glucose homeostasis and energy metabolism. The endogenous ligand of GCGR is glucagon, primarily secreted by pancreatic α-cells, which plays a pivotal role in maintaining fasting blood glucose levels, promoting lipid oxidation, and increasing energy expenditure.

Glucagon-like peptide-1 receptor (GLP-1R) agonists have revolutionized the treatment of type 2 diabetes and obesity over the past decade. However, the efficacy ceiling of single-target drugs and gastrointestinal tolerance issues have prompted researchers to explore more complex multi-target synergistic strategies.

IL-23 and IL-17A do not function in isolation but form a complete signaling axis from innate immunity to adaptive immunity, and from antigen presentation to tissue inflammation. The core components of this axis include: IL-23 activates the STAT3-RORγt transcriptional program via IL-23R, driving Th17 cell differentiation; Th17 cells secrete IL-17A and IL-17F; IL-17A activates the NF-κB and MAPK pathways in target tissues through IL-17RA/IL-17RC, inducing the expression of inflammatory genes.

IL-23 and IL-17A do not function in isolation but form a complete signaling axis from innate immunity to adaptive immunity, and from antigen presentation to tissue inflammation. The core components of this axis include: IL-23 activates the STAT3-RORγt transcriptional program via IL-23R, driving Th17 cell differentiation; Th17 cells secrete IL-17A and IL-17F; IL-17A activates the NF-κB and MAPK pathways in target tissues through IL-17RA/IL-17RC, inducing the expression of inflammatory genes.

IL-17A is the most functionally critical member of the IL-17 family and serves as the core effector molecule in Th17 immune responses. Unlike its upstream regulatory factor IL-23, IL-17A directly acts on target tissues (such as skin keratinocytes, synovial fibroblasts, and intestinal epithelial cells), inducing the expression of chemokines, cytokines, and antimicrobial peptides, thereby driving neutrophil recruitment and tissue inflammation.

IL-23 is a key member of the IL-12 cytokine family and plays a central regulatory role in coordinating adaptive immune responses. Since its discovery in 2000, IL-23 and its receptor IL-23R have been identified as the dominant signals for Th17 cell differentiation and maintenance, making them strategic targets for drug development in autoimmune diseases such as psoriasis, inflammatory bowel disease, and ankylosing spondylitis.

The development history of KRAS inhibitors spans over thirty years, with the first two decades nearly stagnant and the last decade witnessing an explosion. The turning point lies in the new understanding of KRAS's dynamic conformations and advancements in chemical technologies—particularly the application of covalent chemistry, fragment-based drug design, and targeted protein degradation.

CD3E and CD3D are core subunits of the CD3 complex associated with the T-cell receptor, playing indispensable roles in T-cell development, antigen recognition, and immune activation. With the rapid advancements of T-cell engager (TCE) bispecific antibodies in the fields of oncology and autoimmune diseases, CD3 has become one of the most translatable tool targets in immunotherapy. In April 2026, talquetamab, the world's first DLL3×CD3 TCE for solid tumors, was approved for marketing in China, marking the entry of CD3-targeted therapies into a new era of solid tumor treatment. This article systematically reviews the biological functions and clinical translation progress of CD3E and CD3D from four dimensions: molecular structure, signal transduction mechanisms, associations with immunodeficiency diseases, and the current status of TCE drug development, providing a comprehensive reference for professionals in the biopharmaceutical industry.