What is IGF-1 LR3?
IGF-1 LR3 is a synthetic, structurally modified analog of insulin-like growth factor 1 (IGF-1) studied in research for its altered binding kinetics at the IGF-1 receptor and its attenuated affinity for insulin-like growth factor binding proteins (IGFBPs). It is catalogued under CAS number 946870-92-4, with a molecular weight of 9117.5 g/mol and the molecular formula C₄₀₀H₆₂₅N₁₁₁O₁₁₅S₉. The compound is supplied as a lyophilized powder held to a purity specification of 99.1% and is stored at −20°C. All material is intended solely for research purposes and is not for human or animal use.
The designation "LR3" encodes two structural differences from native IGF-1: a leucine substitution at position 2, an arginine substitution at position 3 (replacing the native glutamate), and a 13-amino acid N-terminal extension. These modifications were introduced in the research literature specifically to investigate the role of IGFBP binding on IGF-1 receptor engagement, making IGF-1 LR3 a mechanistic tool compound rather than a simple replica of the endogenous peptide.
What is the molecular structure of IGF-1 LR3?
IGF-1 LR3 has a molecular weight of 9117.5 g/mol and the molecular formula C₄₀₀H₆₂₅N₁₁₁O₁₁₅S₉. It is a single-chain 83-amino acid peptide — native human IGF-1 is 70 amino acids; the LR3 variant carries a 13-amino acid N-terminal extension in addition to the two point substitutions that define the LR3 modification. The compound retains the three disulfide bridges characteristic of native IGF-1, which are critical to the structural fold required for IGF-1 receptor engagement.
The compound is produced through solid-phase peptide synthesis or recombinant production methods followed by purification, and research-grade material is characterized to a purity specification of 99.1% by HPLC. The lyophilized form is a white to off-white powder. As a larger-format peptide (9117.5 g/mol is substantially larger than most small synthetic peptides in the research catalog), structural integrity is sensitive to temperature excursion, oxidation, and disulfide bond disruption, making cold storage conditions relevant to research reproducibility.
What is the LR3 modification and why is it studied?
Native IGF-1 circulates in biological systems predominantly in a protein-bound form rather than as a free peptide. The binding proteins responsible — collectively referred to as insulin-like growth factor binding proteins, or IGFBPs — include at least six identified family members, with IGFBP-3 being the predominant carrier. These binding proteins regulate the free concentration of IGF-1 available to engage the IGF-1 receptor (IGF-1R) and influence its half-life in circulation.
The research problem that motivated the LR3 modification was straightforward: if native IGF-1 is sequestered by binding proteins, studying isolated IGF-1R engagement kinetics requires a variant that is not subject to the same level of IGFBP interference. The glutamate-to-arginine substitution at position 3 and the N-terminal extension together substantially reduce affinity for IGFBPs while preserving IGF-1R binding. In research models, this produces a compound with extended effective half-life relative to native IGF-1 — not through lipidation (as in some other research peptides), but through reduced IGFBP sequestration.
This makes IGF-1 LR3 useful in research settings specifically for characterizing IGF-1R signaling without the confounding variable of IGFBP-mediated modulation. Researchers studying concentration-response relationships at the IGF-1 receptor use IGF-1 LR3 in contexts where controlling the free-fraction variable is methodologically important.
What receptor does IGF-1 LR3 engage?
The primary research target of IGF-1 LR3 is the insulin-like growth factor 1 receptor (IGF-1R), a transmembrane receptor tyrosine kinase. IGF-1R is a heterotetrameric receptor composed of two extracellular alpha subunits and two membrane-spanning beta subunits, linked by disulfide bridges. The alpha subunits contain the ligand-binding domains; the beta subunits carry the intracellular tyrosine kinase domains that are activated upon ligand binding.
IGF-1 LR3 also has measurable affinity for the insulin receptor (IR) — particularly the IR-A isoform — because the structural similarities between IGF-1 and insulin produce overlapping binding compatibility with both receptors. The relative affinity for IGF-1R versus IR is a variable that researchers characterize in binding assays as part of selectivity profiling for IGF-family analogs. The IGF-2 receptor (IGF-2R / mannose-6-phosphate receptor) also binds IGF family members, but via a distinct mechanism not involving tyrosine kinase signaling; research on IGF-1 LR3 is typically focused on IGF-1R engagement rather than IGF-2R interactions.
What downstream signaling pathways are characterized in IGF-1 LR3 research?
Ligand binding to IGF-1R triggers receptor autophosphorylation at multiple tyrosine residues in the intracellular kinase domain. This autophosphorylation creates docking sites for adaptor proteins, initiating two well-characterized downstream signaling cascades that are the focus of IGF-1R research:
PI3K/Akt/mTOR pathway. Receptor activation recruits insulin receptor substrate proteins (IRS-1 and IRS-2) to the phosphorylated receptor. IRS proteins then recruit and activate phosphoinositide 3-kinase (PI3K), which phosphorylates membrane phospholipids to generate PIP3. PIP3 recruits Akt (also referred to as protein kinase B, PKB) to the plasma membrane, where it is phosphorylated and activated. Downstream targets of Akt include mTOR (mechanistic target of rapamycin), FOXO transcription factors, and BAD, placing this pathway at the intersection of cell survival and protein synthesis signaling research. The mTOR complex 1 (mTORC1) branch regulates S6 kinase (S6K) and 4E-BP1, two translational regulators that are frequently used as readouts for IGF-1R pathway activation in research assays.
Ras/MAPK/ERK pathway. IRS protein activation also drives recruitment of the Grb2-SOS adaptor complex, which activates the small GTPase Ras. Activated Ras initiates the MAPK kinase cascade through Raf, MEK, and ERK. ERK signaling is studied in the context of cell cycle progression and transcription factor activation in IGF-1R research models. The PI3K/Akt and MAPK/ERK branches operate in parallel from the IGF-1R and can interact through cross-regulatory nodes, a complexity that makes dissecting individual branch contributions a subject of ongoing mechanistic investigation.
Research using IGF-1 LR3 characterizes these signaling outputs in cell-culture and preclinical models. AminoKinetics makes no therapeutic or outcome claims regarding IGF-1 LR3; the compound is studied for its effects on these receptor kinetics and signaling pathway mechanisms in research settings only.
How does IGF-1 LR3 differ from native IGF-1 in research models?
The key distinctions that make IGF-1 LR3 a distinct research tool rather than an equivalent substitute for native IGF-1 are structural and kinetic:
| Property | Native IGF-1 | IGF-1 LR3 |
|---|---|---|
| Amino acid length | 70 aa | 83 aa (13 aa N-terminal extension) |
| Position 3 residue | Glutamate (E3) | Arginine (R3) |
| IGFBP binding affinity | High (predominantly IGFBP-3 bound) | Substantially reduced |
| Effective half-life in research models | Short (IGFBP-regulated) | Extended (reduced IGFBP sequestration) |
| IGF-1R binding | High affinity | High affinity (retained) |
| Research utility | Characterizing endogenous IGF-1 biology | Isolating IGF-1R signaling without IGFBP modulation |
Researchers selecting between native IGF-1 and IGF-1 LR3 for an assay should be aware that the modification is not neutral — it changes the compound's biological context in ways that are the point of its design. For experiments investigating IGFBP biology or the regulatory role of binding proteins in IGF-1 signaling, native IGF-1 may be the appropriate tool. For experiments focused on IGF-1R kinetics and downstream pathway activation with a controlled free-fraction variable, LR3 is the compound the literature uses for that purpose.
What handling conditions apply to IGF-1 LR3 in research?
IGF-1 LR3 is supplied as a lyophilized powder and stored at −20°C to preserve structural integrity. At 9117.5 g/mol, it is a larger peptide than most compounds in the research catalog, and its disulfide-bond-dependent structure is sensitive to reducing conditions, oxidation, and temperature excursion. Research handling practices that support reproducibility include maintaining cold storage, minimizing freeze-thaw cycle exposure, and protecting lyophilized material from humidity and reducing agents.
Cold-chain handling during shipping is directly relevant for the same reasons. The three intramolecular disulfide bridges that maintain the native fold of IGF-1 LR3 are the structural basis for receptor engagement; disrupting them through improper thermal handling compromises the compound's research value regardless of what the original COA documented. AminoKinetics ships all compounds cold-chain packaged as standard.
This article does not provide preparation or reconstitution instructions; handling protocols are determined by the researcher according to experimental requirements and applicable regulations.
How does AminoKinetics supply IGF-1 LR3?
AminoKinetics supplies IGF-1 LR3 as a research-grade compound held to a purity specification of 99.1% by HPLC, with mass spectrometry identity confirmation. Every order ships with a batch-specific Certificate of Analysis, and all shipments are cold-chain packaged as standard. Researchers can review specifications, available sizes, and pricing on the IGF-1 LR3 compound page, or browse the full research catalog at all compounds. For an overview of how to interpret the analytical documentation shipped with each order, see our article on analytical standards for research peptide sourcing.
All material is intended for laboratory research use only, not for human or animal use.
This compound is a research chemical intended for laboratory and scientific research purposes only. It is not a drug, supplement, or food, and is not intended to diagnose, treat, cure, or prevent any disease. AminoKinetics does not sell products intended for human or animal use. Researchers are responsible for compliance with all applicable local, state, and federal regulations governing the purchase and use of research materials.