Anti-Human IGF-1R Monoclonal Antibody (Teprotumumab)

IGF-1R (insulin-like growth factor 1 receptor) is a receptor tyrosine kinase widely distributed across human cells, forming a heterotetrameric structure composed of two α subunits and two β subunits linked by disulfide bonds. The α subunits are located extracellularly and are responsible for recognizing and binding ligands (IGF-1 and IGF-2, with lower affinity for insulin), while the β subunits traverse the cell membrane and possess tyrosine kinase activity within their intracellular domains. Upon ligand binding to the α subunits, conformational changes in the β subunits trigger autophosphorylation, thereby activating two classical intracellular downstream signaling pathways: the PI3K-AKT pathway, which primarily mediates cell survival and metabolic regulation, and the Ras-MAPK pathway, which promotes cell proliferation and differentiation. IGF-1R is indispensable for normal growth and development in individuals; however, its hyperactivation or overexpression is closely associated with various pathological conditions. Notably, in cancer, it drives malignant tumor progression by inhibiting apoptosis and promoting proliferation, invasion, and metastasis, while also mediating resistance to radiotherapy and targeted therapies. Furthermore, dysregulation of the IGF-1R signaling pathway is also implicated in fibroproliferative diseases such as idiopathic pulmonary fibrosis. Consequently, this protein has emerged as a highly promising therapeutic target in the fields of oncology and fibrotic diseases, although the clinical application of targeted drugs still faces challenges regarding efficacy and safety.