Research summary
IGF-1 LR3 — clinical & mechanistic profile
IGF-1 LR3 is a synthetic 83-amino-acid IGF-1 analog with an Arg3 substitution and 13-aa N-terminal extension that reduces IGFBP binding, extending half-life from ~15 min to 20-30 hours. Activates PI3K/Akt/mTOR pathway for protein synthesis while suppressing FoxO-mediated ubiquitin-proteasome degradation via GSK3β inhibition.
Research status
preclinical
Molecular weight
9111.2 g/mol
Molecular formula
C400H625N111O115S9
Studied applications
- •Extended half-life: 20-30 hours vs. ~15 min for native IGF-1 due to reduced IGFBP binding
- •PI3K/Akt/mTOR activation: stimulates protein synthesis via mTOR, S6K1, and 4E-BP1 phosphorylation
- •Catabolic suppression: inhibits FoxO transcription factors and E3 ubiquitin ligases, reducing proteolysis
- •GH synergy: co-administration with GH enhances anabolism; GH drives endogenous IGF-1 production
- •Satellite cell activation: stimulates muscle stem cell proliferation and differentiation for hypertrophy
Mechanisms of action
- •IGF-1R activation: binds IGF-1 receptor tyrosine kinase, triggering autophosphorylation and IRS-1 recruitment
- •PI3K/Akt cascade: activates protein synthesis via mTOR, S6K1, 4E-BP1; increases ribosome biogenesis
- •GSK3β inhibition: Akt-mediated inhibition prevents glycogen synthase inactivation and muscle catabolism
- •FoxO suppression: phosphorylation causes nuclear exclusion, reducing atrogene and E3 ligase expression
- •Insulin receptor cross-activation: lower-affinity activation of insulin receptor amplifies effects post-exercise
- •Reduced IGFBP interaction: N-terminal extension and Arg3 substitution prevent binding protein sequestration
Research constraints & safety notes
- •Not approved for human use in any jurisdiction
- •Prohibited by WADA under S2 category (Peptide Hormones, Growth Factors)
- •Potent growth factor activity raises significant safety concerns including cancer risk
- •No human clinical trials conducted for any indication
- •Hypoglycemia risk due to structural similarity to insulin
Peer-reviewed references
For research use only. This summary is a research-scientific overview compiled from peer-reviewed sources. It is not medical advice and is not intended for human or veterinary consumption.
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