Insulin-like growth factor 1 (IGF1) (IGF1)

Insulin-like growth factor 1 (IGF1) is a potent anabolic hormone primarily produced by the liver in response to stimulation by growth hormone (GH). It serves as a critical mediator of the systemic effects of GH, promoting longitudinal bone growth, tissue repair, and cellular proliferation across various organ systems. IGF1 exerts its biological effects by binding to the IGF1 receptor (IGF1R), a tyrosine kinase receptor, which activates signaling pathways such as PI3K/Akt and MAPK to promote cell survival and inhibit apoptosis. In clinical practice, IGF1 is a central target for both replacement therapy and inhibition. Recombinant human IGF1 (mecasermin) is used to treat severe primary IGF1 deficiency, while the suppression of IGF1 production is a primary therapeutic goal in the management of acromegaly and certain cancers where IGF1 signaling drives tumor progression. Targeting IGF1 at the mRNA level using antisense oligonucleotides or RNA interference represents an emerging strategy to precisely downregulate its expression in pathological states like hyperproliferative disorders and specific malignancies.

Other names

Somatomedin CIGF-IMechano growth factorMGFIGF1A

Drugs targeting IGF1 mRNA, such as antisense oligonucleotides (ASOs), utilize Watson-Crick base pairing to bind to the messenger RNA sequence, leading to RNase H-mediated degradation of the transcript or steric hindrance of translation, thereby reducing the production of the IGF1 protein. Recombinant IGF1 protein acts as an agonist at the IGF1 receptor (IGF1R) to stimulate growth, while somatostatin analogs and GH receptor antagonists reduce endogenous IGF1 levels by inhibiting the growth hormone axis.