IGF-1 LR3 Research, Specifications & Scientific Information

IGF-1 LR3 is a recombinant analogue of human insulin-like growth factor 1 carrying a 13-residue N-terminal extension and an arginine substitution at position 3. It was built as a laboratory reagent for studying the IGF-binding proteins, it has never been studied in a clinical trial, and it is not approved by the FDA for any indication.

By Elegance Peptides Editorial TeamPublished September 22, 2026Updated September 22, 2026

Category: IGF and growth-factor peptides

Introduction

IGF-1 LR3 is the only compound in this batch that was never intended to become a medicine. It was built in an Adelaide laboratory in the early 1990s as a research tool, and its design goal was unusual: not a better agonist, but a worse ligand for something else. Insulin-like growth factor 1 circulates almost entirely bound to a family of binding proteins that control how much of it reaches a receptor. To study what those proteins do, the investigators needed an IGF-1 that could evade them, and they made one by adding a 13-residue N-terminal extension and substituting arginine for glutamate at position 3 ^[3].

The result is frequently described as a more potent IGF-1. That is true only in the presence of binding proteins, and it is worth understanding why, because the same paper reports that in a cell line secreting no detectable binding proteins the analogue was less potent than native IGF-1, and a companion study measured it binding the type 1 IGF receptor about threefold less well ^{[3, 2]}. It has no clinical literature at all, and this page does not borrow one from native IGF-1.

What Is IGF-1 LR3?

IGF-1 LR3 is a recombinant 83-residue protein expressed in Escherichia coli. Its two parts are separable in the name itself.

"Long" is the N-terminal extension: methionine, the first eleven amino acids of porcine growth hormone, then valine and asparagine — MFPAMPLSSLFVN. This was not decoration. The investigators reported that a hydrophobic N-terminal extension facilitated the correct oxidative folding of the IGF-1 analogues, giving high yields of biologically active product where folding normal-length IGFs had been harder ^[3].

"R3" is the substitution: arginine in place of the glutamate at position 3 of the IGF-1 sequence. The same fusion construction was made with glycine at that position, and with no substitution at all, producing a graded series — Long [Arg3]-IGF-I, Long [Gly3]-IGF-I and Long IGF-I — whose comparison is the point of the experiment ^[3].

It is not an approved medicine anywhere, it has not been the subject of any clinical trial, and it has never been developed as a candidate for one. Its entire published record is in vitro and animal work, much of it using the analogue as an instrument for asking questions about the binding proteins rather than about the analogue itself.

IGF-1 LR3 Specifications

Compound name: IGF-1 LR3
Full chemical name: Long-(Arg3)-insulin-like growth factor-I
Aliases: Long R3 IGF-I, LR3IGF-I, Long [Arg3]-IGF-I, insulin-like growth factor long chain R3
Development code: Not publicly characterised
CAS number: 143045-27-6
PubChem CID: Not publicly characterised
UNII: M9L22Y19H9
Compound type: Recombinant protein analogue (growth factor)
Peptide family: Insulin-like growth factor family
Amino acid sequence: MFPAMPLSSLFVNGPRTLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA
Sequence length: 83 residues
Molecular formula: Not publicly characterised
Molecular weight: 9117.6 g/mol
Primary target: Type 1 insulin-like growth factor receptor (IGF-1R)
Secondary targets: Insulin receptor, in cell systems where the insulin-like growth factors act through it
Receptor family: Receptor tyrosine kinases
Agonist / antagonist status: Agonist at the type 1 IGF receptor, binding it approximately threefold less well than native IGF-1

The 83-residue chain above is the sequence recorded in the FDA/NCATS Global Substance Registration System under UNII M9L22Y19H9 for the substance the register names Long-(Arg3)-insulin-like growth factor-I. It resolves into two parts. Residues 1 to 13, MFPAMPLSSLFVN, are the N-terminal extension: methionine plus the first eleven amino acids of porcine growth hormone, followed by valine and asparagine. Residues 14 to 83 are the 70-residue human insulin-like growth factor 1 sequence with one substitution, arginine in place of glutamate at IGF-1 position 3 — visible in the chain above as GPRT where native IGF-1 reads GPET. The register records no further structural modifications; the three disulphide bonds that give the IGF-1 domain its fold are not written into a single-letter string. The register carries CAS registry number 143045-27-6 for this substance. A different registry number, 946870-92-4, appears in the supplier catalog and in many commercial listings for material sold under this name; the number published here is the register's, and the discrepancy is recorded rather than resolved. No PubChem compound identifier resolves for this analogue, and no molecular formula is published for it by a register, so both fields are shown as unknown. The molecular weight is the supplier catalog reference value. The certificate of analysis supplied with a laboratory order is the record for a given lot.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does IGF-1 LR3 Work?

The receptor is the type 1 insulin-like growth factor receptor, a receptor tyrosine kinase closely related to the insulin receptor — closely enough that the 1986 determination of its primary structure was framed as a comparison between the two, looking for the structural determinants of their functional specificity ^[1]. IGF-1 LR3 is an agonist at that receptor, and nothing about its engineering changes which receptor it engages.

What the engineering changes is availability. Circulating insulin-like growth factors are largely bound to IGF-binding proteins, which regulate their transfer from blood to tissue sites of action. An analogue that binds those proteins poorly is not sequestered in the same way. That is the whole mechanism, and it has a direct and testable consequence: the analogue's apparent potency should depend on how much binding protein is present in the system being used to measure it.

That prediction was tested, and it held — in both directions.

IGF-1 LR3 Mechanism of Action

In vitro research

In L6 rat myoblasts, all of the Long IGF-I analogues were more potent than authentic IGF-1 at stimulating protein synthesis and DNA synthesis and at inhibiting protein breakdown. In H35 hepatoma cells, where the insulin-like growth factors act through the insulin receptor, the Long analogues held a similar potency relative to IGF-1 as they had in the myoblasts ^[3].

The ordering in cell lines that secrete IGF-binding proteins into the medium was: Long [Arg3]-IGF-I and des(1-3)IGF-I above Long [Gly3]-IGF-I, above Long IGF-I, above native IGF-1 — exactly the order of decreasing binding-protein affinity ^[3].

The control that makes the argument is the negative one. In chicken embryo fibroblasts, a cell line that secretes no detectable IGF-binding proteins into the medium, Long [Arg3]-IGF-I was less potent than IGF-1 ^[3]. Direct measurement of receptor and binding-protein association in the same study confirmed the interpretation: the increased biological potency of these N-terminal analogues is attributable to changes in their binding-protein interactions, not to improved receptor engagement. A companion study put a number on the receptor side, reporting that the analogue binds the type 1 IGF receptor approximately threefold less well than IGF-1 ^[2].

Anyone quoting a potency multiple for this analogue is quoting a property of the assay system as much as of the molecule.

What Is IGF-1 LR3 Being Researched For?

The honest answer is that it is mostly used to research something else. Published work using this analogue falls into:

The function of the IGF-binding proteins — the purpose it was built for, and the subject of the comparisons above ^{[3, 4]}.
Plasma clearance and tissue distribution — how a poorly bound IGF behaves in a whole animal ^{[5, 7, 10]}.
Anabolic and gastrointestinal rodent models — where it serves as the high-availability comparator against native IGF-1 ^{[2, 6, 8]}.
Assay development — an immunoassay specific to the substituted analogue ^[9].

There is no human research on this analogue. Clinical data for recombinant human insulin-like growth factor 1 concern the native 70-residue sequence, a different molecule without the extension or the substitution, and nothing in that record transfers to this one. That distinction is the single most important thing on this page.

Preclinical Research on IGF-1 LR3

Animal research

The clearest animal demonstration of the binding-protein argument came from a catabolic rat model. Male rats of about 150 g received dexamethasone at 20 µg per day, which produced a catabolic state, with IGF-1 or its analogues delivered by subcutaneously implanted osmotic pump. Native IGF-1 partially reversed the catabolism, with effects on body weight and nitrogen retention that graded with the amount administered: at the highest amount, 695 µg per day, body weight rose 6 g over seven days against a 19 g loss in the dexamethasone-only group and an 18 g gain in pair-fed controls ^[2].

Two analogues that bind the binding proteins poorly — the truncated des(1-3)IGF-1 and LR3IGF-I — were approximately 2.5-fold more potent than IGF-1 in that model. The authors singled out the LR3 result as striking precisely because the peptide binds the type 1 IGF receptor threefold less well than IGF-1 does. Their explanation was the binding proteins: dexamethasone combined with IGF-1 raised plasma IGF-binding protein 3 substantially, and those proteins would be expected to reduce the transfer of IGF-1, but not of the variants, from blood to tissue. Measurements of muscle protein synthesis and of protein breakdown by 3-methylhistidine excretion indicated coordinate effects on both processes; excretion fell from 83.5 ± 4.2 to 65.1 ± 2.2 µmol/kg per 7 days at the highest amount of IGF-1, against 54.9 ± 1.2 in pair-fed controls ^[2].

A later study asked whether that advantage was an artefact of continuous infusion — a reasonable worry, since a molecule that escapes sequestration might behave differently under a bolus. It did not: the superior potency of the poorly binding analogues under infusion was maintained when they were administered by injection ^[6].

Gut tissue has been a recurring model. Systemic infusion of IGF-1 or LR3IGF-I in suckling rats stimulated visceral organ growth and proliferation of gut tissues ^[8].

Findings described in this section were observed in animals, and nothing in them establishes anything about humans.

Other Areas of IGF-1 LR3 Research

Animal research

The pharmacokinetic literature exists because the analogue's whole premise is a change in distribution rather than in receptor activity, and distribution is measurable. Labelled IGF-1 and LR3IGF-I were compared for plasma clearance and tissue distribution in pregnant rats ^[5], and the broader question of how binding-protein interactions govern clearance and in vivo activity across the IGFs and their analogues was reviewed in the same period ^[4].

Disease states that alter binding-protein handling were an obvious test. Plasma clearance of IGF-1, des-(1-3)IGF-1 and LR3IGF-I was compared in chronic renal failure, a condition in which IGF-binding protein concentrations are disturbed ^[7]. A later study compared intestinal delivery of the analogue and of IGF-1 in preweaning and adult rats, finding delivery to the intestine differed between the two ^[10].

Supporting all of this is a methodological point that is easy to overlook: measuring an engineered analogue in plasma requires an assay that can tell it apart from the endogenous hormone. A non-competitive enzyme-linked immunosorbent assay was developed using a monoclonal antibody raised against an epitope containing the substituted arginine at position 3; it detected as little as 50 pg of the analogue in 100 µl, with native IGF-1 and IGF-2 showing less than 0.01 per cent cross-reactivity, and its response was unaffected by the presence of IGF-binding proteins ^[9].

Findings described in this section were observed in animals.

Current Research Status

Regulatory status (United States): Not approved. This analogue has not been approved by the U.S. Food and Drug Administration for any indication, and no product containing it has been submitted for approval.
Investigational status: No clinical trial of this analogue has been identified in public trial registers or in the peer-reviewed literature. It was designed as a laboratory reagent for investigating the role of the insulin-like growth factor binding proteins, and that is the role it has occupied since. Human clinical data exist for recombinant human insulin-like growth factor 1 of the native sequence, which is a structurally different molecule and whose record is not evidence about this one.
Highest research phase reached: No clinical study identified; in vitro and animal research only
Approved uses: None
Approval is compound-specific: No

Status as of September 22, 2026. This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

Chemical & Molecular Characteristics

IGF-1 LR3 is a recombinant protein, and its register record is more complete than most compounds in this catalogue on sequence and less complete on almost everything else.

The sequence is a register record. MFPAMPLSSLFVNGPRTLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA is the 83-residue chain recorded under UNII M9L22Y19H9 for Long-(Arg3)-insulin-like growth factor-I. Residues 1 to 13 are the extension; residues 14 to 83 are the substituted IGF-1 sequence.

The single-letter string omits the disulphides. The IGF-1 domain is held in its fold by three disulphide bonds between its six cysteines, and the register's structural-modification list for this substance is empty — the folding is implicit in the sequence, not written into it. A linear string is not a statement that the protein is linear.

The registry numbers disagree. The register carries CAS 143045-27-6. The supplier catalog and many commercial listings carry 946870-92-4. This page publishes the register's number and records the discrepancy rather than resolving it, because resolving it would require a source neither register provides.

Two fields are blank on purpose. No PubChem compound identifier resolves for this analogue, and no register publishes a molecular formula for it. Both are shown as unknown. The molecular weight of 9117.6 g/mol is the supplier catalog reference value, and the certificate of analysis for a given lot is the record for that lot.

Analytical Specifications

Physical form: Lyophilized powder
Appearance: White to off-white lyophilized solid
Lot number: RP-2609-079
Tested purity: ≥99% by HPLC
Storage: −20 °C, protect from light, desiccate

Analytical figures are lot-specific. Fields the catalog does not carry for the current lot are omitted rather than filled with a typical value. The certificate of analysis and the safety data sheet for the exact lot supplied are provided with a laboratory order; no purity figure on this page is a substitute for that document.

Frequently Asked Questions

What is IGF-1 LR3?

IGF-1 LR3 is a recombinant analogue of human insulin-like growth factor 1. It consists of the 70-residue IGF-1 sequence with arginine substituted for glutamate at position 3, preceded by a 13-residue N-terminal extension made of methionine, the first eleven amino acids of porcine growth hormone, valine and asparagine ^[3]. It was created as a laboratory reagent for investigating IGF-binding protein function.

What does the name mean?

“Long” refers to the N-terminal extension; “R3” refers to the arginine at position 3 of the IGF-1 portion. The same construction was made with glycine at that position, giving Long [Gly3]-IGF-I, and without any substitution, giving Long IGF-I ^[3]. The register records the substance as Long-(Arg3)-insulin-like growth factor-I.

How does IGF-1 LR3 work?

It is an agonist at the type 1 insulin-like growth factor receptor, a receptor tyrosine kinase whose primary structure was determined in 1986 ^[1]. The engineering does not target that receptor — it targets the IGF-binding proteins, which sequester circulating insulin-like growth factors. The analogue binds those proteins poorly, so more of it reaches the receptor ^[3].

Why is IGF-1 LR3 described as more potent than IGF-1?

Only where binding proteins are present, and not because it engages the receptor more strongly. In cell lines secreting IGF-binding proteins into the medium, the order of potency ran Long [Arg3]-IGF-I and des(1-3)IGF-I above Long [Gly3]-IGF-I, above Long IGF-I, above native IGF-1. In chicken embryo fibroblasts, which secrete no detectable binding proteins, Long [Arg3]-IGF-I was less potent than native IGF-1 ^[3]. It also binds the type 1 IGF receptor about threefold less well than IGF-1 does ^[2].

Is IGF-1 LR3 FDA approved?

No. This analogue has not been approved by the U.S. Food and Drug Administration for any indication, and no product containing it has been submitted for approval.

Has IGF-1 LR3 been studied in humans?

No published clinical study of this analogue has been identified, and no trial of it appears in public registers. The published literature is in vitro work and animal work, chiefly in rats. Clinical data that exist for recombinant human insulin-like growth factor 1 concern the native 70-residue sequence, which is a structurally different molecule; those data are not evidence about this analogue.

How does IGF-1 LR3 differ from IGF-1?

By 13 extra residues at the N-terminus and one substitution inside the IGF-1 sequence. Native IGF-1 reads GPET at its first four positions; the analogue reads GPRT. Both differences were introduced to reduce binding to the IGF-binding proteins, and the N-terminal extension also improved the yield of correctly folded protein during production ^[3].

What identifiers are published for IGF-1 LR3?

The FDA/NCATS Global Substance Registration System carries the substance under UNII M9L22Y19H9 with CAS registry number 143045-27-6 and the full 83-residue sequence. A different registry number circulates in commercial listings, including the catalog entry for this reagent; the register’s number is the one published here and the discrepancy is recorded rather than resolved. No PubChem compound identifier resolves for the analogue, and no register publishes a molecular formula for it, so both fields are shown as unknown.

Scientific References

Ullrich A, Gray A, Tam AW, et al.. Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity The EMBO journal; 1986. PMID 2877871 doi:10.1002/j.1460-2075.1986.tb04528.x
Tomas FM, Knowles SE, Owens PC, et al.. Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic in dexamethasone-treated rats The Biochemical journal; 1992. PMID 1371669 doi:10.1042/bj2820091
Francis GL, Ross M, Ballard FJ, 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 Journal of molecular endocrinology; 1992. PMID 1378742 doi:10.1677/jme.0.0080213
Ballard FJ, Walton PE, Bastian S, et al.. Effects of interactions between IGFBPs and IGFs on the plasma clearance and in vivo biological activities of IGFs and IGF analogs Growth regulation; 1993. PMID 7683526
Bastian SE, Walton PE, Wallace JC, et al.. Plasma clearance and tissue distribution of labelled insulin-like growth factor-I (IGF-I) and an analogue LR3IGF-I in pregnant rats The Journal of endocrinology; 1993. PMID 7693845 doi:10.1677/joe.0.1380327
Tomas FM, Lemmey AB, Read LC, et al.. Superior potency of infused IGF-I analogues which bind poorly to IGF-binding proteins is maintained when administered by injection The Journal of endocrinology; 1996. PMID 8708565 doi:10.1677/joe.0.1500077
Gillespie CM, Hazel SJ, Walton PE, et al.. Effects of chronic renal failure on plasma clearance of insulin-like growth factor I, des-(1-3)IGF-I, and LR3IGF-I The American journal of physiology; 1996. PMID 8897852 doi:10.1152/ajpendo.1996.271.4.E649
Steeb CB, Shoubridge CA, Tivey DR, et al.. Systemic infusion of IGF-I or LR(3)IGF-I stimulates visceral organ growth and proliferation of gut tissues in suckling rats The American journal of physiology; 1997. PMID 9124573 doi:10.1152/ajpgi.1997.272.3.G522
Gajanandana O, Irvine K, Grant PA, et al.. Measurement of an analog of insulin-like growth factor-I in blood plasma using a novel enzyme-linked immunosorbent assay The Journal of endocrinology; 1998. PMID 9582496 doi:10.1677/joe.0.1560407
Shoubridge CA, Read LC. Preferential intestinal delivery of long[Arg3] insulin-like growth factor (LR3IGF-I) over IGF-I in preweaning and adult rats Endocrinology; 2003. PMID 12697696 doi:10.1210/en.2002-220643

Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.

Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.