IGF-1 LR3

Why scientists study it

• It is more potent than natural IGF-1 in many tests because it binds weakly to IGFBPs, the binding proteins that usually lock up IGF-1 in the blood.
• It is a standard lab tool for switching on IGF-1R in cell studies of muscle formation, fibroblast growth and organ growth, where slipping past the binding proteins removes a major cause of test-to-test variation.
• In muscle models it sends a tissue-building signal through PI3K, Akt and mTOR, while the MAP kinase branch separately drives the cell division response described in L6 myoblast work.

Three studies to know

1992 · Journal of Molecular Endocrinology

This paper by Francis and colleagues took apart the effects of the two changes, the Arg 3 swap and the extension at the N-terminal end. The two changes roughly add up in lowering affinity for IGFBPs. The potency edge over natural IGF-1 vanished in cell systems with no IGFBPs. That is direct evidence that the extra potency comes from slipping past IGFBPs. Read the paper

1992 · Journal of Molecular Endocrinology

Using Escherichia coli, King and colleagues made and described recombinant IGF-I along with potent fusion-protein analogs changed at the N-terminal end. Some carried the Gly 3 or the Arg 3 swap. This is the founding production work behind LR3-IGF-I as a lab reagent. Read the paper

2008 · Nature Reviews Cancer

This review by Pollak covers the evidence on insulin and IGF-1 signaling in tumor growth. The review gives the cancer context for any potent compound that switches on IGF-1R. It also gives the reason to block IGF-1R with drugs in cancer treatment. Read the paper

Safety and legal status

• No group of people has been exposed to IGF-1 LR3 for study. All population data concern the body’s own IGF-1 or mecasermin used in clinics. Safety views on LR3 are drawn from animal drug studies. No controlled human trial of LR3 stands behind them.
• It is not FDA approved for any use. The WADA Prohibited List bans IGF-1 and IGF-1 analogs by name at all times, under class S2.
• Mecasermin (Increlex) is a different thing. It is a recombinant human IGF-1 drug with its own approval, for primary IGF-1 deficiency that is severe. The body handles IGF-1 LR3 differently, and LR3 is only a research reagent. It is for use in laboratory research and nothing else.