Insulin-like growth factor 1 (IGF-1) receptor is a transmembrane receptor. Specifically, it belongs to a large class of tyrosine kinase receptors. This receptor mediates the action of IGF-1, a polypeptide protein hormone with a molecular structure similar to insulin. Besides, IGF-1 plays an important role in the growth and continues to play an anabolic role in adults. Moreover, IGF1R binds IGF1 with high affinity and IGF2 and insulin (INS) with low affinity. Ligand binding activates receptor kinase, leading to receptor self-phosphorylation and tyrosine phosphorylation of various substrates. Furthermore, this then activates two major signaling pathways: PI3K-AKT/PKB pathway and Ras MAPK pathway. Receptor activation is relevant to cell growth and survival control.
Because IGF1R is widely expressed in the whole body, IGF1R mutation leads to systematic disorder of growth and glucose homeostasis. Meanwhile, IGF1R mutations can affect ligand binding and/or reduce surface IGF1R expression. Nonetheless, IGF1 activates mitogen-activated protein (MAP) kinase and PI3K signal pathway and promotes tissue growth and maturation by up-regulating anabolic process. Mutations that reduce IGF1 signaling activity can significantly prolong the life span of organisms. Here, we will introduce an IGF1R mAb, Ganitumab.
Ganitumab (AMG 479) is an IGF1R mAb for Cancer Research.
At first, Ganitumab (AMG 479) is a recombinant human monoclonal antibody to the human type 1 insulin-like growth factor receptor (IGF1R). Importantly, Ganitumab recognizes murine IGF1R with sub-nanomolar affinity (KD=0.22 nM). Particularly, Ganitumab inhibits the interaction of murine IGF1R with IGF1 and IGF2. Ganitumab can be used in research on cancer.
Secondly, Ganitumab with 0.032-500 nM binds mIGF1R and inhibits IGF1- and IGF2-mediated activation of mIGF1R in CT26 cells. Obviously, Ganitumab with 1 mg/dose by i.p inhibits IGF1-induced activation of mIGF1R in murine lungs. Interestingly, Ganitumab reduces peripheral blood neutrophils. Additionally, Ganitumab causes impaired glucose tolerance in male mice and increases serum levels of mGH, mIGF1 and mIGFBP3.
Finally, Ganitumab (AMG 479) is a recombinant human monoclonal antibody to the IGF1R.
References:
Moody G, et, al. J Endocrinol. 2014 Mar 17;221(1):145-55.