Insulin-like growth factor 1 receptor and Insulin receptor (IGF-1R and IR)

The insulin-like growth factor 1 receptor (IGF-1R) and the insulin receptor (IR) are closely related, large, transmembrane tyrosine kinase receptors that regulate diverse cellular processes, including growth, proliferation, differentiation, survival, and metabolism[1][3][6]. Both receptors are tetrameric, consisting of two extracellular α-subunits for ligand binding and two transmembrane β-subunits containing the catalytic kinase domains[1][6][9]. IGF-1R is primarily activated by insulin-like growth factors (IGF-1 and IGF-2), whereas IR primarily binds insulin, but both can interact with each other’s ligands to a limited degree—and can form hybrid receptors with distinct biological properties[5][3]. IGF-1R signaling fosters cell proliferation and inhibits apoptosis, thus playing a major role in fetal and postnatal growth and tissue homeostasis. Overexpression or upregulation of IGF-1R is frequently observed in tumors and is associated with cancer cell survival, while IR dysregulation is central to disorders like diabetes and metabolic syndrome[6][7][8][9]. As pharmacological targets, therapies blocking either receptor can impair growth signaling in cancer or modulate glucose homeostasis, but therapeutic targeting is complicated by essential roles in normal tissue growth and metabolism[7][9].

Other names

IGF1 receptor (IGF1R)Insulin receptor (INSR)Type 1 insulin-like growth factor receptorType 2 insulin receptor (for certain isoforms/hybrids)

Inhibition of IGF-1R or IR tyrosine kinase activity. Blockade of ligand binding (antibody mechanism). Downregulation of receptor expression. Modulation of downstream PI3K/AKT/mTOR and Ras/MAPK pathways.