IGF-1 LR3 Liquid Spray 2mg

Mucosal-delivery research format of the long-acting IGF-1 analog. Supports laboratory protocols investigating non-injectable peptide delivery routes for growth-factor research. HPLC-tested, third-party COA per batch.

$100.00

SKU: OM-SPRY-IGF1LR3-2MG Category:

Description

IGF-1 LR3 (also known as Long-R3-IGF-1 or LR3-IGF-1; CAS 946870-92-4) is an 83-amino-acid synthetic analog of native human insulin-like growth factor 1 (IGF-1). The molecule retains the complete 70-amino-acid native IGF-1 sequence with two structural modifications — a 13-amino-acid N-terminal extension (the “Long” designation) and an arginine-for-glutamic-acid substitution at position 3 (the “R3” designation) — which together reduce binding affinity to circulating IGF binding proteins (IGFBPs) by approximately 600-fold while preserving full agonist activity at the IGF-1 receptor. The pharmacology of the native IGF-1 system has been characterized in peer-reviewed studies published in the New England Journal of Medicine, Endocrine Reviews, and other top journals, and the IGF-1 LR3 analog has been characterized in the American Journal of Physiology — Endocrinology and Metabolism and Drug Testing and Analysis.

The structural modifications extend plasma half-life from approximately 10–20 minutes for native IGF-1 to approximately 20–30 hours for IGF-1 LR3, producing a substantially different pharmacokinetic profile than the native molecule despite identical receptor pharmacology [1].

Important Note on the Evidence Base

Important note on the evidence base: The clinical evidence on the IGF-1 axis derives largely from trials of recombinant human IGF-1 (rhIGF-1, sold as mecasermin / Increlex®), which is FDA-approved for severe primary IGF-1 deficiency in pediatric patients. IGF-1 LR3 itself has not been clinically developed in humans; the published research on the LR3 analog specifically is primarily in (a) mechanistic and pharmacokinetic studies in animals and isolated tissues, (b) cell culture applications (it is widely used as a serum-free supplement for stem cell and cell-line maintenance), and (c) analytical/anti-doping methodology (LR3 is on the World Anti-Doping Agency prohibited list). The studies summarized below reflect this evidence-base structure.

Published Research on IGF-1 LR3 and the IGF-1 Axis

The following peer-reviewed studies are summarized below. Full citations and direct links to each publication appear in the References section.

Pharmacokinetics in Calves — Hammon & Blum, American Journal of Physiology — Endocrinology and Metabolism (1997)

Hammon and Blum at the University of Bern evaluated the somatotropic axis effects of subcutaneous and oral Long-R3-IGF-I administration in neonatal calves during the first week of life. The study compared subcutaneous and oral routes (50 µg·kg-1·day-1 for 7 days) against recombinant bovine GH and dietary intervention, measuring plasma IGF-I, IGF-II, IGF-binding proteins, and GH.

The investigators reported that plasma Long-R3-IGF-I increased significantly after subcutaneous administration but not after oral administration; native IGF-I was lowered by subcutaneous LR3 administration through negative feedback on the somatotropic axis; and parenteral LR3 decreased GH concentration without affecting the secretory pattern [1]. The study established the bioavailability and feedback profile of LR3-IGF-I after subcutaneous administration in a mammalian system.

Read the full study: The Somatotropic Axis in Neonatal Calves Can Be Modulated by Nutrition, Growth Hormone, and Long-R3-IGF-I (AJP-Endo 1997).

Native rhIGF-1 in IGF-1 Deficiency — Chernausek et al., Journal of Clinical Endocrinology & Metabolism (2007)

Chernausek and colleagues conducted the pivotal long-term clinical trial of recombinant human IGF-1 (mecasermin) in pediatric patients with severe primary IGF-1 deficiency — the trial that supported FDA approval of Increlex® for this rare growth-failure population. The trial enrolled 76 children with severe IGFD and followed them for up to 8 years on twice-daily subcutaneous mecasermin administration, with growth velocity, height standard-deviation score, and adverse events as primary endpoints.

The investigators reported sustained increases in growth velocity over 8 years of mecasermin treatment, with a favorable safety profile in this pediatric population [2]. The trial established the IGF-1 axis as a clinical therapeutic target and supports the broader pharmacological rationale for IGF-1 receptor agonism, of which IGF-1 LR3 is one analog with extended pharmacokinetic properties.

Read the full study: Long-Term Treatment with Recombinant Insulin-Like Growth Factor (IGF)-I in Children with Severe IGF-I Deficiency Due to Growth Hormone Insensitivity (JCEM 2007).

Detection in Doping Analysis — Mongongu et al., Drug Testing and Analysis (2021)

Mongongu and colleagues at the French Anti-Doping Laboratory developed and validated a sensitive analytical method for detecting Long-R3-IGF-I, Des(1–3)-IGF-I, and R3-IGF-I in human serum using immunopurification followed by nano-liquid chromatography coupled with high-resolution mass spectrometry. The investigators characterized analytical performance (linearity, detection limits, precision, specificity) and evaluated detection windows in rats following single intramuscular administration of each analog.

The authors reported that Long-R3-IGF-I disappeared rapidly from circulation after 4 hours following intramuscular administration in rats, while the related analogs Des(1–3)-IGF-I and R3-IGF-I remained detectable for up to 24 hours [3]. The investigators also identified oxidized forms in confiscated black-market products, indicating quality concerns in the gray-market supply. The study is the foundation for current anti-doping detection of IGF-1 analogs.

Read the full study: Detection of LongR3-IGF-I, Des(1-3)-IGF-I, and R3-IGF-I Using Immunopurification and High Resolution Mass Spectrometry for Antidoping Purposes (Drug Test Anal 2021).

Cell Culture Applications — Cell Sciences Technical Literature

The widespread use of Long-R3-IGF-I as a recombinant cell-culture supplement is documented in technical and methods literature published by manufacturers and end users in pharmaceutical bioprocessing, stem-cell maintenance, and other in vitro applications. The 200-fold-greater potency of LR3 versus insulin in cell-culture systems — coupled with the molecule’s resistance to enzymatic degradation in serum-free media — underlies its adoption as a substitute for native IGF-1 in animal-component-free cell-culture protocols.

The IGF-1 LR3 cell-culture application literature documents the molecule’s bioactivity at sub-nanomolar concentrations in human pluripotent stem-cell maintenance, hybridoma cell lines, CHO cell expression systems, and primary mammalian cell isolations [4]. These applications are the predominant published use case for LR3 specifically.

Industrial and methods literature, including Cell Sciences technical documentation on LONG R3 IGF-I.

About the Compound

Native human IGF-1 is a 70-amino-acid single-chain protein with three intramolecular disulfide bonds, structurally homologous to proinsulin and produced primarily in the liver in response to growth hormone stimulation. It mediates most of the systemic effects of growth hormone through agonism at the IGF-1 receptor (IGF-1R), a transmembrane tyrosine-kinase receptor expressed on most tissues. In circulation, the bioavailability of native IGF-1 is tightly regulated by a family of six IGF binding proteins (IGFBP-1 through IGFBP-6), which sequester ~99% of plasma IGF-1 and limit its receptor-accessible fraction.

IGF-1 LR3 was developed in the late 1980s and early 1990s as an analog with reduced IGFBP binding for cell-culture and research applications. The 13-amino-acid N-terminal extension (sequence MFPAMPLLSLFVN) shifts the three-dimensional conformation of the binding interface, while the Arg3→Glu3 substitution disrupts a key contact residue with IGFBPs. The result is a molecule with 600-fold reduced IGFBP affinity and approximately 3-fold greater potency at the IGF-1 receptor in cell-culture assays. The same modifications produce the extended plasma half-life (~20–30 h) that distinguishes LR3 from native IGF-1 (~10–20 min) in animal studies.

  • CAS Number: 946870-92-4 (also reported as 143045-27-6 for the related sequence)
  • Molecular Formula: C400H625N111O115S9
  • Molecular Weight: ~9,111 Da (83 amino acids)
  • Synonyms: Long-R3-IGF-1, Long Arg3-IGF-I, LR3-IGF-1, LONG®R3 IGF-I
  • Receptor target (in research literature): IGF-1 receptor (IGF-1R)
  • Plasma half-life (LR3): Approximately 20–30 hours (vs. 10–20 minutes for native IGF-1)
  • Regulatory status (as of publication): Not approved by any regulatory authority. Native rhIGF-1 (mecasermin / Increlex®) is FDA-approved for severe primary IGF-1 deficiency. IGF-1 analogs including LR3 are on the WADA prohibited list for athletic competition.

Product Specifications

Omnix Peptides supplies IGF-1 LR3 as a pre-mixed liquid intranasal spray in a sealed metered nasal spray bottle intended exclusively for in vitro laboratory research. Each production lot is independently characterized using high-performance liquid chromatography (HPLC) and liquid chromatography–mass spectrometry (LC–MS) protocols.

  • Format: Liquid intranasal spray
  • Strength: 2 mg of peptide per 30 mL bottle
  • Verified Purity: >99% (HPLC, LC–MS)
  • Container: Sealed metered nasal spray bottle
  • Documentation: Batch-specific Certificate of Analysis (COA) available

Storage, handling, intended-use, and regulatory information are provided in the corresponding tabs on this product page.

References

  1. Hammon HM, Blum JW. The somatotropic axis in neonatal calves can be modulated by nutrition, growth hormone, and Long-R3-IGF-I. Am J Physiol. 1997;273(1 Pt 1):E130-E138. doi:10.1152/ajpendo.1997.273.1.E130
  2. Chernausek SD, Backeljauw PF, Frane J, Kuntze J, Underwood LE; GH Insensitivity Syndrome Collaborative Group. Long-term treatment with recombinant insulin-like growth factor (IGF)-I in children with severe IGF-I deficiency due to growth hormone insensitivity. J Clin Endocrinol Metab. 2007;92(3):902-910. doi:10.1210/jc.2006-1610
  3. Mongongu C, Coudoré F, Domergue V, Ericsson M, Buisson C, Marchand A. Detection of LongR3-IGF-I, Des(1-3)-IGF-I, and R3-IGF-I using immunopurification and high resolution mass spectrometry for antidoping purposes. Drug Test Anal. 2021;13(7):1256-1269. doi:10.1002/dta.3016
  4. Cell Sciences. Quantitation of LONG®R3 IGF-I During Production and Cell Culture Application: Technical Whitepaper. View whitepaper.
For research use only. Not for human consumption.