Overview
IGF-1 LR3 (Insulin-like Growth Factor-1 Long Arg3) is a synthetic, elongated analog of the naturally occurring insulin-like growth factor-1, a peptide that plays a key role in cellular growth and metabolism in mammals. It was engineered to have a modified amino acid sequence — specifically an arginine substitution at position 3 and an additional 13-amino acid extension at the N-terminus — which extends its activity compared to the native IGF-1 molecule by reducing its binding to IGF-binding proteins. As a growth factor peptide, IGF-1 LR3 belongs to the insulin-like growth factor family and is of significant interest in preclinical and laboratory research settings. Scientists have studied it in contexts ranging from muscle tissue repair and nerve regeneration to fetal development models, as seen in published research exploring its behavior in various biological systems. IGF-1 LR3 is intended strictly for research purposes and is not approved for human use or consumption.
Research & Bioactivity
IGF-1 LR3 is a synthetic analogue of insulin-like growth factor-1 (IGF-1) that researchers have studied across a range of biological contexts, including muscle tissue repair, nerve regeneration, fetal development, and neurological function. In animal models, studies have examined the peptide's potential role in volumetric muscle loss, investigating whether controlled local delivery could support tissue repair following severe muscle injury. Research has also investigated IGF-1 LR3 as a component of engineered nerve conduit systems in rat models, exploring how its controlled release may influence peripheral nerve regeneration alongside biomaterial scaffolds. Studies using transgenic mouse models of Alzheimer's disease have examined intranasal administration of LR3 IGF-1 in relation to amyloid plaque dynamics and cognitive markers, with researchers noting mixed outcomes that underscore the complexity of IGF-1 signaling in the central nervous system. Additionally, in vivo research using fetal sheep models has explored how IGF-1 LR3 relates to fetal growth and metabolic regulation under conditions of placental insufficiency, contributing to a broader understanding of IGF-1's role in anabolic signaling during development. These studies collectively reflect scientific interest in IGF-1 LR3 as a research tool for investigating growth factor biology across multiple physiological systems.
Published Research
Provisional Treatment of Volumetric Muscle Loss With Insulin-like Growth Factor 1 Releasing Muscle Void Fillers.
Clark AR, Adams AT, McKinley TO, Natoli RM, Dearth CL, et al. — 2026
INTRODUCTION: Volumetric muscle loss (VML) resulting from severe extremity injuries in combat remains a significant clinical challenge, particularly in austere environments. Current research emphasizes the development and evaluation of definitive treatments, largely neglecting acute stabilization strategies. To address this unmet need, this study investigated the efficacy of delivering insulin-like growth factor 1 long arginine 3 (IGF1-LR3) via a synthetic in situ forming hydrogel muscle void filler (MVF) to enhance muscle recovery after VML. METHODS: Adult male Lewis rats underwent VML surgery, followed by implantation of a polyethylene glycol-acrylate MVF containing either soluble or poly(lactic-co-glycolic acid) (PLGA)-encapsulated IGF1-LR3 at a low (28 μg) or high (280 μg) dose, or no IGF1-LR3 (control). Neuromuscular function was assessed via isometric torque measurements. Muscle tissue was analyzed using wheat germ agglutinin and picrosirius red staining for fiber size, count, and fibrosis. Statistical analysis was performed using ANOVA with Holm-Šídák post hoc testing. RESULTS: High-dose PLGA-encapsulated IGF1-LR3 resulted in increased muscle weight compared to the control group at 28 d post implantation. However, no differences were observed in specific torque or maximum torque production between any experimental groups. Histological analysis revealed no changes in muscle fibrosis or fiber size or count of IGF1-LR3 compared to controls. CONCLUSIONS: The addition of IGF1-LR3 in an MVF did not enhance neuromuscular function or muscle fiber hypertrophy. Further studies are needed to optimize IGF1-LR3 delivery or alternative hypertrophy-inducing soluble factors.
Revolutionary decellularized Alstroemeria stem-based nerve conduit integrated with GelMA and controlled IGF-1 LR3 release for enhanced rat sciatic nerve regeneration.
Yavuz E, Sağır MS, Ercan A, Erginer M, Barlas FB, et al. — 2025
Peripheral nerve injuries lead to significant functional deficits, with no treatment achieving complete recovery. Autologous nerve grafting remains the gold standard, but it is limited by donor site morbidity. Artificial nerve conduits have been developed but have not matched the outcomes of autologous grafts. This study introduces the first-ever decellularized plant-based nerve conduit, fabricated from Alstroemeria stem material, integrated with GelMA, and featuring controlled release of Insulin-like Growth Factor Long Arginine 3 (IGF-1 LR3) for enhanced axonal regeneration. Thirty rats were assigned to six experimental groups (n = 5) and underwent a 1 cm sciatic nerve defect. Regeneration was assessed via gait analysis, electrophysiology, histology, and immunohistochemistry, comparing the decellularized conduit to autologous grafts and commercial conduits. The IGF-1 LR3-controlled releasing decellularized conduit significantly improved axonal regeneration and showed comparable performance to autologous nerve grafts, without inducing systemic toxicity. This novel conduit demonstrates the potential of plant-based biomaterials for effective peripheral nerve repair.
IGF-1 LR3 does not promote growth in late-gestation growth-restricted fetal sheep.
White A, Stremming J, Wesolowski SR, Al-Juboori SI, Dobrinskikh E, et al. — 2025
Insulin-like growth factor-1 (IGF-1) and insulin are important fetal anabolic hormones. Complications of pregnancy, such as placental insufficiency, can lead to fetal growth restriction (FGR) with low-circulating IGF-1 and insulin concentrations and attenuated glucose-stimulated insulin secretion (GSIS), which likely contribute to neonatal glucose dysregulation. We previously demonstrated that a 1-wk infusion of IGF-1 LR3, an IGF-1 analog with low affinity for IGF-binding proteins and high affinity for the IGF-1 receptor, at 6.6 µg·kg·h into normal fetal sheep increased body weight but lowered insulin concentrations and GSIS. In this study, FGR fetal sheep received either IGF-1 LR3 treatment at 1.17 ± 0.12 μg·kg·h (LR3; = 7) or vehicle (VEH; = 7) for 1 wk. Plasma insulin, glucose, oxygen, and amino acids were measured before starting treatment and at the end of the treatment period. GSIS was measured on the final treatment day. Fetal body weights, insulin, glucose, oxygen, and GSIS were not different between groups. Amino acid concentrations decreased in LR3 (baseline vs. final individual means comparison = 0.0232) but not in VEH ( = 0.3866). In summary, a 1-wk IGF-1 LR3 treatment did not improve growth in FGR fetuses. Insulin concentrations and GSIS were not attenuated by IGF-1 LR3, yet circulating amino acids decreased, which could reflect increased amino acid utilization. We speculate that maintaining amino acid concentrations or raising insulin, glucose, and/or oxygen concentrations to values consistent with normally growing fetuses during IGF-1 LR3 treatment may be necessary to increase fetal growth in the setting of placental insufficiency and FGR. IGF-1 LR3 treatment administered directly into growth-restricted fetal sheep circulation did not improve fetal growth or attenuate circulating insulin or fetal GSIS. Importantly, IGF-1 LR3 treatment reduced circulating amino acids, notably branched-chain amino acids, which have been shown to potentiate GSIS and protein accretion supporting fetal growth.
Intranasal long R3 insulin-like growth factor-1 treatment promotes amyloid plaque remodeling in cerebral cortex but fails to preserve cognitive function in male 5XFAD mice.
Engel MG, Narayan S, Cui MH, Branch CA, Zhang X, et al. — 2025
BACKGROUND: Insulin-like growth factor-1 (IGF-1) promotes neurogenesis, cell survival, and glial function, making it a promising candidate therapy in Alzheimer's disease (AD). OBJECTIVE: Long arginine 3-IGF-1 (LR3-IGF-1) is a potent IGF-1 analogue. We sought to determine whether intranasal (IN) LR3 treatment would delay cognitive decline and pathology in 5XFAD mice. METHODS: Wildtype and 5XFAD male mice were treated for 7 months (3-10 months of age), with IN LR3-IGF-1 or IN Vehicle (Veh) (n = 19-27 mice/group). Behavior, memory, and brain imaging were assessed at 8-9 months of age and tissues collected at 10 months. A comprehensive amyloid-β (Aβ) profile and other pathologic features were conducted and supportive stimulation studies in BV-2 microglial cells were also performed. RESULTS: In male 5XFAD mice, IN LR3-IGF-1 treatment improved body composition, but did not significantly alter cognitive symptoms, as assessed by multiple assays. In cortex, LR3 treatment improved some facets of pathology, including a reduction in filamentous plaques, and increase in inert plaques, corresponding with a reduction in low molecular weight Aβ oligomers. , uptake of Aβ peptide by BV2 cells was enhanced by LR3-IGF-1, which was also found to promote gene pathways implicated in actin remodeling and endocytosis. CONCLUSIONS: LR3 promotes favorable effects on Aβ plaque remodeling in cortex of male 5XFAD mice but fails to preserve aspects of behavior or memory. While these data do not support LR3 as a monotherapy , they do warrant further investigation into its potential for combinatorial formulations aimed at targeting the complexity of AD.
Recombinant expression of IGF-1 and LR3 IGF-1 fused with xylanase in Pichia pastoris.
Lu Z, Liu N, Huang H, Wang Y, Tu T, et al. — 2023
Insulin-like growth factor-1 (IGF-1) is a pleiotropic protein hormone and has become an attractive therapeutic target because of its multiple roles in various physiological processes, including growth, development, and metabolism. However, its production is hindered by low heterogenous protein expression levels in various expression systems and hard to meet the needs of clinical and scientific research. Here, we report that human IGF-1 and its analog Long R3 IGF-1 (LR3 IGF-1) are recombinant expressed and produced in the Pichia pastoris (P. pastoris) expression system through being fused with highly expressed xylanase XynCDBFV. Furthermore, purified IGF-1 and LR3 IGF-1 display excellent bioactivity of cell proliferation compared to the standard IGF-1. Moreover, higher heterologous expression levels of the fusion proteins XynCDBFV-IGF-1 and XynCDBFV-LR3 IGF-1 are achieved by fermentation in a 15-L bioreactor, reaching up to about 0.5 g/L XynCDBFV-IGF-1 and 1 g/L XynCDBFV-TEV-LR3 IGF-1. Taken together, high recombinant expression of bioactive IGF-1 and LR3 IGF-1 is acquired with the assistance of xylanase as a fusion partner in P. pastoris, which could be used for both clinical and scientific applications. KEY POINTS: • Human IGF-1 and LR3 IGF-1 are produced in the P. pastoris expression system. • Purified IGF-1 and LR3 IGF-1 show bioactivity comparable to the standard IGF-1. • High heterologous expression of IGF-1 and LR3 IGF-1 is achieved by fermentation in a bioreactor.