IGF-1 LR3

What it is

IGF-1 LR3 is a synthetic analogue of human IGF-1 that differs by having an arginine substitution at position 3 and an N-terminal extension peptide. Its defining pharmacological property is dramatically reduced binding affinity for IGF-binding proteins (IGFBPs), estimated at least 3 orders of magnitude lower than native IGF-1, combined with retained high affinity for the IGF-1 receptor (IGF-1R) (PMID 19633297; PMID 33938236). Because it is not sequestered by IGFBPs, LR3-IGF-1 has greater bioavailability in extravascular spaces and is cleared more rapidly from wounds than native IGF-1 (half-life in wound fluid ~563 min vs. ~872 min for IGF-1). Downstream signalling occurs through IGF-1R activation of the ERK (MAPK) and PI3K/Akt pathways (PMID 12947030; PMID 36499281; PMID 16397250). LR3-IGF-1 does not significantly stimulate IGFBP-4 proteolysis because it lacks affinity for IGFBP-3, unlike native IGF-1. It is described as 2.5–3 times more potent than native IGF-1 in restoring growth in diabetic rats. In the performance-enhancing drug context, it is classified among unregulated GH-IGF-1 axis-modulating peptides.

Class: Insulin-like growth factor-1 (IGF-1) analogue / synthetic peptide

What it's studied for

• Fetal growth and organ development (sheep model) Animal studies only
  • 1-week intravenous infusion of LR3 IGF-1 into late-gestation fetal sheep increased heart, adrenal gland, and spleen weights and stimulated skeletal muscle myoblast proliferation, but did not significantly increase total fetal weight; umbilical amino acid uptake rates and fetal arterial amino acid and insulin concentrat PMID 33427051 Stremming et al., Am J Physiol Endocrinol Metab (2021)
  • 1-week IGF-1 LR3 treatment in growth-restricted fetal sheep did not improve fetal growth, body weight, insulin, or glucose-stimulated insulin secretion, but circulating amino acids (notably branched-chain) decreased. PMID 39679943 White et al., Am J Physiol Endocrinol Metab (2025)
  • IGF-1 LR3 administration to near-term fetal sheep (127–134 d gestation) increased fetal heart mass and cardiomyocyte proliferation; coronary conductance was preserved on a per-gram basis, and coronary vascular function was maintained. PMID 32573852 Jonker et al., FASEB J (2020)
  • In vivo LR3 IGF-1 administration to fetal sheep decreased the percentage of binucleated cardiomyocytes; in vitro LR3 IGF-1 increased myocyte BrdU uptake 3- to 5-fold, abolished by ERK or PI3K blockade. PMID 12947030 Sundgren et al., Am J Physiol Regul Integr Comp Physiol (2003)
  • LR3 IGF-1 infusion into fetal sheep previously shown to increase fetal organ growth and skeletal muscle myoblast proliferation; this study used sheep-specific recombinant IGF-1 to overcome low IGFBP affinity limitations of LR3 IGF-1. PMID 36091374 Stremming et al., Front Physiol (2022)
• Fetal insulin secretion and islet function (sheep model) Animal studies only
  • 1-week IGF-1 LR3 infusion into late-gestation fetal sheep lowered plasma insulin and glucose concentrations, reduced fetal glucose-stimulated insulin secretion (GSIS), and caused an intrinsic islet defect in isolated fetal islets. PMID 33938236 White et al., Am J Physiol Endocrinol Metab (2021)
  • Acute 90-min IGF-1 LR3 infusion suppressed fetal plasma insulin and hyperglycemic-clamp insulin concentrations; however, insulin secretion from isolated fetal islets was not different, suggesting the β-cell retains ability to recover GSIS after short-term exposure. PMID 37114757 White et al., J Dev Orig Health Dis (2023)
• Alzheimer's disease / amyloid pathology (mouse model) Animal studies only
  • 7-month intranasal LR3-IGF-1 treatment in male 5XFAD mice improved body composition and reduced filamentous plaques in cortex with increased inert plaques and reduced low-molecular-weight Aβ oligomers, but did not significantly alter cognitive symptoms as assessed by multiple behavioural assays. PMID 39610283 Engel et al., J Alzheimers Dis (2025)
• Volumetric muscle loss / muscle repair Animal studies only
  • IGF1-LR3 delivered via synthetic hydrogel muscle void filler at low (28 µg) or high (280 µg) dose in Lewis rat VML model: high-dose PLGA-encapsulated IGF1-LR3 increased muscle weight vs. control at 28 d, but no differences in specific or maximum torque, fibrosis, or fiber size/count were observed. PMID 41015370 Clark et al., J Surg Res (2026)
• Peripheral nerve regeneration Animal studies only
  • Decellularized plant-based nerve conduit with controlled release of IGF-1 LR3 significantly improved axonal regeneration in rat sciatic nerve defect model with performance comparable to autologous grafts and no systemic toxicity noted. PMID 41015370 Yavuz et al., Int J Biol Macromol (2025)
• Growth promotion in neonatal pigs Animal studies only
  • LR3IGF-I infusion at 8 µg/h then 16 µg/h in artificially-reared neonatal pigs increased daily weight gain in the second 9-day period (457 vs. 386 g/d, P<0.01) and was more potent than native IGF-I; LR3IGF-I decreased plasma IGF-I concentrations. PMID 12067429 Dunshea et al., Br J Nutr (2002)
• Growth restoration in diabetic rats Animal studies only
  • LR3-IGF-I was 2.5–3 times more potent than native IGF-1 in restoring growth and nitrogen balance in streptozotocin-diabetic rats; did not decrease glucosuria unlike insulin; increased muscle protein synthesis rates and RNA levels. PMID 7683875 Tomas et al., Biochem J (1993)
• Cancer cachexia / muscle wasting Animal studies only
  • In a C26-CD2F1 mouse cachexia model, LR3 IGF-I treatment limited loss of muscle mass but was associated with accelerated tumour growth. In vitro, LR3 IGF-I increased differentiation index and nuclei count in C2C12 skeletal muscle cells. PMID 31285507 Levolger et al., Sci Rep (2019)
• Tumour growth / oncology (in vitro and in vivo as research ligand) Mixed
  • In tumour-bearing rats, LR3-IGF-I infusion (200 or 500 µg/day) increased tumour growth more than native IGF-I, decreased food intake, lowered circulating insulin and glucose, and did not promote muscle protein accretion; co-infusion with insulin had synergistic effect on host weight. PMID 8053901 Tomas et al., Biochem J (1994)
  • LR3 IGF-I used as a stimulatory ligand in cell-based assays to characterise IGF-IR inhibitor BMS-554417; LR3 IGF-I stimulated cyclin D1 nuclear accumulation and cell cycle progression, effects blocked by BMS-554417. PMID 16397250 Haluska et al., Cancer Res (2006)
• Mammary gland / lactation enhancement (mouse) Animal studies only
  • Subcutaneous injection of long-R3-IGF-I in lactating mice modestly increased lactation capacity, increased mammary phospho-Akt and SOCS3 gene expression. PMID 18577570 Hadsell et al., J Endocrinol (2008)
• Rumen Na+ transport (sheep in vitro model) Animal studies only
  • LR3-IGF-1 at 20–100 µg/L applied serosally rapidly (within 30 min) stimulated mucosal-to-serosal Na+ flux and net Na+ flux across isolated rumen epithelium by ~60%; effect mediated by Na+-H+ exchange (NHE). PMID 22227200 Shen et al., Exp Physiol (2012)
• Small intestinal growth and mucosal development Animal studies only
  • Review: LR3-IGF-I administration by osmotic pump affects the small intestine similarly to IGF-I but with higher potency; generally increases mucosal cellularity without consistently altering intestinal weight or length. PMID 10226789 MacDonald, Horm Metab Res (1999)
• Ovarian follicle / granulosa-theca cell research (tool compound) Animal studies only
  • LR3 IGF-I increased bovine preantral follicle diameter in dose-dependent manner and increased estradiol production, but at studied doses also caused smaller oocyte/follicle ratios and increased oocyte degeneration vs. physiological hrIGF-I doses. PMID 17636166 Thomas et al., Reproduction (2007)
  • LR3-IGF-1 (50 ng/ml) markedly increased output of inhibin A, activin A, follistatin, estradiol, and progesterone by bovine mural granulosa cells in vitro; oocytes suppressed these IGF-induced responses. PMID 12604623 Glister et al., Biol Reprod (2003)
• IGF-1 receptor signalling studies (in vitro tool compound) In vitro only
  • LR3-IGF-I used to stimulate IGF-1R without IGFBP interference in MCF-10A breast epithelial cells; IGFBP-3 potentiated LR3-IGF-I-stimulated IGFR1 phosphorylation and DNA synthesis via SphK1/S1P pathway. PMID 19633297 Martin et al., J Biol Chem (2009)
  • IGF-1 LR3 stimulation of CHO cells showed significantly reduced ERK1/2 phosphorylation in N-glycosylation-deficient mutants (Lec1, Lec4), demonstrating N-glycosylation is critical for IGF-1R-dependent ERK signalling. PMID 36499281 Salvi et al., Int J Mol Sci (2022)
  • LR3-IGF-I stimulated IGF-1R phosphorylation to a greater extent than native IGF-I at 5 and 10 wk of age in mice, regardless of gender or genotype. PMID 16166219 Oliver et al., Endocrinology (2005)
• Recombinant protein production / biomanufacturing In vitro only
  • LR3 IGF-1 expressed in Pichia pastoris fused with xylanase XynCDBFV reached ~1 g/L in 15-L bioreactor fermentation; purified LR3 IGF-1 displayed bioactivity of cell proliferation comparable to standard IGF-1. PMID 37261455 Lu et al., Appl Microbiol Biotechnol (2023)
  • Physicochemical characterisation of LR3-IGF1 protein inclusion bodies; isoelectric point and electrophoretic mobility data relevant to recovery process design. PMID 11485445 Wangsa-Wirawan et al., Biotechnol Prog (2001)

Community-reported dosing

Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.