What IGF-1 LR3 is
IGF-1 LR3, also written Long R3 IGF-I or LR3IGF-I, is an engineered analog of human insulin-like growth factor-I (IGF-I). Native IGF-I is a 70-amino-acid single-chain polypeptide hormone. It is structurally related to proinsulin and is produced mainly in the liver in response to growth hormone.
IGF-1 LR3 was developed in the early 1990s by researchers in Adelaide, Australia. They were studying why IGF-I’s activity is so strongly regulated by a family of carrier proteins, the IGF-binding proteins (IGFBPs). The analog was designed as a research reagent: a version of IGF-I that interacts only weakly with IGFBPs, so that receptor-mediated effects could be separated from binding-protein effects.
The material A&A Wellness supplies as IGF-1 LR3 is for laboratory research only. It is not a drug, food, cosmetic or supplement, and it is not for human or veterinary use.
Classification and structure
From 70 to 83 amino acids
IGF-1 LR3 differs from native IGF-I in two ways:
- The “Long” extension. A 13-amino-acid sequence is added to the N-terminus. It consists of the first 11 residues of methionyl porcine growth hormone followed by a Val-Asn linker. This brings the total length to 83 amino acids.
- The “R3” substitution. The glutamic acid at position 3 of the IGF-I sequence is replaced with arginine.
Francis and colleagues described the expression system and the family of fusion analogs, including “Long IGF-I,” “Long [Gly3]-IGF-I” and “Long [Arg3]-IGF-I,” in the Journal of Molecular Endocrinology in 1992 (Francis et al., J Mol Endocrinol 1992). A companion paper from the same group characterized recombinant IGF-I and its Gly3 and Arg3 variants produced in E. coli (King et al., J Mol Endocrinol 1992).
A recombinant protein, not a short synthetic peptide
At 83 residues with three disulfide bonds, IGF-1 LR3 is a small recombinant protein, not a short synthetic peptide. The original work described producing it in bacteria as a fusion protein, then refolding and purifying it. Correct disulfide pairing is essential to its activity. For that reason, analytical characterization of this compound (see peptide purity: HPLC and mass spectrometry) is more demanding than for a five- or ten-residue peptide.
Mechanism as described in the literature
IGFBPs as gatekeepers
In circulation and in tissue fluids, most native IGF-I is bound to one of six IGFBPs, mainly in a ternary complex with IGFBP-3 and the acid-labile subunit. Binding extends IGF-I’s half-life but also limits how much free hormone can reach the IGF-I receptor (IGF-1R), a receptor tyrosine kinase.
What the modifications change
King and colleagues reported that the [Gly3] and [Arg3] variants bound very poorly to an IGF-binding protein and slightly less well than IGF-I to the type-1 IGF receptor. They concluded that reduced IGFBP binding, not increased receptor binding, was the likely explanation for the variants’ greater potency in rat myoblast assays (King et al., J Mol Endocrinol 1992).
Francis and colleagues extended this work to the “Long” fusion analogs. In cell lines that secrete IGFBPs into the culture medium, they reported a potency order with Long [Arg3]-IGF-I at the top and native IGF-I at the bottom. In chicken embryo fibroblasts, which do not secrete detectable IGFBPs, Long [Arg3]-IGF-I was less potent than IGF-I. That result supports the interpretation that the analog’s apparent potency depends on escaping binding proteins. The authors also noted that the hydrophobic N-terminal extension appeared to help the analogs fold correctly during production (Francis et al., J Mol Endocrinol 1992).
Species differences
Lord and colleagues compared how IGF-I, des(1-3)IGF-I and LR3IGF-I associated with plasma binding proteins from rats, sheep, pigs, humans and chickens. They found marked species differences: variants that bound very weakly in rat plasma bound more in plasma from the other species (Lord et al., J Endocrinol 1994). This is a useful caution when comparing results across animal models.
Clearance
Because it is less protected by binding proteins, LR3IGF-I was reported to be cleared from the circulation of rats more quickly than native IGF-I (Bastian et al., J Endocrinol 1993; Tomas et al., J Endocrinol 1996). This counterintuitive result is often misunderstood. Lower IGFBP binding makes the analog more available at the receptor, but it circulates for a shorter time.
Research history and key published studies
Development as a reagent (1992)
The Adelaide group’s goal was mechanistic: to find out how much IGF-I’s bioactivity depends on escaping IGFBPs. The 1992 papers established the analogs as tools for that question (Francis et al., 1992; King et al., 1992). Long R3 IGF-I was later adopted widely as a defined supplement in mammalian cell-culture media, where it can replace insulin or serum-derived growth factors.
Rodent physiology studies (1993-1996)
A series of rat studies compared native IGF-I with its variants:
- Diabetic rat model, 1993. In streptozotocin-diabetic rats given infused peptides, des(1-3)IGF-I and LR3-IGF-I were reported to be roughly 2.5 to 3 times more potent than IGF-I at restoring growth. They did not reproduce every characteristic effect of insulin (Tomas et al., Biochem J 1993).
- Pregnant rats, 1993. Studies of plasma clearance and tissue distribution used radiolabelled peptides to compare where IGF-I and LR3IGF-I went after administration (Bastian et al., J Endocrinol 1993).
- Infusion vs injection, 1996. A follow-up study compared continuous infusion with injection in normal and dexamethasone-treated rats. It reported that LR3IGF-I kept greater potency than IGF-I for several measures even when given by injection, although not for every endpoint studied (Tomas et al., J Endocrinol 1996).
Preclinical and in-vitro only. These studies used rodent models and cell systems. We are not aware of controlled clinical trials of IGF-1 LR3 in humans in the peer-reviewed literature, and no regulatory authority has evaluated it for any clinical use.
Regulatory status
- Not an approved drug. IGF-1 LR3 is not FDA-approved for any use.
- Do not confuse it with mecasermin. Mecasermin is recombinant native human IGF-1. It is the active ingredient in an approved prescription product for a specific paediatric growth disorder. It has the native 70-residue sequence and is a different molecule from IGF-1 LR3.
- Sport rules. IGF-1 and its analogs are included on the World Anti-Doping Agency’s prohibited list.
- Research material only. A&A Wellness’s IGF-1 LR3 is sold for in-vitro and laboratory research only.
For general context, see our regulatory overview. It is not legal advice.
Handling and storage in the lab
As a disulfide-bonded protein, IGF-1 LR3 is more sensitive to handling than most short peptides:
- Lyophilized storage. Keep vials sealed, cold, dry and dark. Freezer storage is common for long-term holding.
- Gentle handling. Protein structure can be damaged by vigorous agitation and foaming. Swirl or roll gently rather than vortexing.
- Mind the vial walls. Low-concentration protein solutions can adsorb to container surfaces. Many laboratories use low-binding plasticware and an appropriate carrier or diluent, following their own validated SOPs.
- Aliquot and label. Aliquot solutions to avoid repeated freeze-thaw cycles, and record the date, diluent and concentration on each tube.
See our peptide storage guide and lyophilized peptides explained.
Research-use notice
All A&A Wellness products are for research use only. They are not for human or veterinary use and are not a drug, food, cosmetic or dietary supplement. This page summarizes published laboratory and animal research and makes no suggestion of personal use. Please review our Research Use Policy before ordering.
Related resources
- Product page: IGF-1 LR3
- Related compounds: Tesamorelin, CJC-1295
- Guide: Growth hormone secretagogues: research overview
- Category: Research Peptides
- Quality: Our quality standards
Sources
- Francis GL, et al. Novel recombinant fusion protein analogues of insulin-like growth factor (IGF)-I indicate the relative importance of IGF-binding protein and receptor binding for enhanced biological potency. J Mol Endocrinol. 1992;8(3):213-223.
- King R, et al. Production and characterization of recombinant insulin-like growth factor-I (IGF-I) and potent analogues of IGF-I, with Gly or Arg substituted for Glu3, following their expression in Escherichia coli as fusion proteins. J Mol Endocrinol. 1992;8(1):29-41.
- Tomas FM, et al. Insulin-like growth factor-I and more potent variants restore growth of diabetic rats without inducing all characteristic insulin effects. Biochem J. 1993;291(Pt 3):781-786.
- Bastian SE, et al. Plasma clearance and tissue distribution of labelled insulin-like growth factor-I (IGF-I) and an analogue LR3IGF-I in pregnant rats. J Endocrinol. 1993;138(2):327-336.
- Lord AP, et al. Differences in the association of insulin-like growth factor-I (IGF-I) and IGF-I variants with rat, sheep, pig, human and chicken plasma-binding proteins. J Endocrinol. 1994;140(3):475-482.
- Tomas FM, et al. Superior potency of infused IGF-I analogues which bind poorly to IGF-binding proteins is maintained when administered by injection. J Endocrinol. 1996;150(1):77-84.
