IGF-1 LR3

IGF-1 LR3 (Long R3 Insulin-like Growth Factor-1) is a synthetic analog of human insulin-like growth factor 1 (IGF-1) designed for extended bioavailability. It consists of the full 70-amino acid IGF-1 sequence plus a 13-amino acid N-terminal extension, with a single amino acid substitution (Glu³ → Arg) that reduces binding affinity for IGF-binding proteins (IGFBPs) by approximately 500-fold.

IGF-1 LR3 is a research compound with no approved indication for human therapeutic use. It is used extensively in cell culture research (as a superior alternative to native IGF-1 for in vitro growth factor supplementation) and in preclinical animal studies. Despite widespread use in performance enhancement communities, no human clinical trials of IGF-1 LR3 have been published.

Note: IGF-1 LR3 is a large recombinant protein (83 amino acids, ~9.1 kDa) — technically at the upper boundary of the "peptide" classification. It is categorized with GH axis peptides by research vendors due to its role in GH/IGF-1 axis signaling.

Native IGF-1 circulates primarily bound to IGFBPs (insulin-like growth factor binding proteins), which extend its plasma half-life but also restrict bioavailability at target tissues. The Glu³ → Arg substitution in LR3-IGF-1 disrupts IGFBP binding at the N-terminal region, resulting in: - Extended plasma half-life: 20–30 hours (vs. 10–16 hours for native IGF-1) - Greater free (bioavailable) fraction at tissues - Superior stimulation of IGF-1R in in vitro and ex vivo systems

Like native IGF-1, LR3-IGF-1 binds the IGF-1 receptor (IGF-1R), a receptor tyrosine kinase, activating two primary downstream pathways: - **PI3K/Akt:** Promotes cell survival, protein synthesis (via mTOR), glucose uptake (GLUT4 translocation) - **MAPK/ERK:** Drives cell proliferation and differentiation

The insulin receptor (IR) is also bound at high concentrations, mediating hypoglycemic effects. Hypoglycemia is the primary safety concern with IGF-1 LR3 use in humans.