IGF-1 LR3 research profile

Key findings

The construct is an IGF-I sequence preceded by the first eleven residues of methionyl porcine growth hormone plus Val-Asn, with Glu3 of the human sequence replaced by arginine, and the cited work attributes its raised potency to changed interaction with the binding proteins rather than to the receptor. [1]
In a cell line that does not secrete detectable binding proteins into the medium, the analogue was less potent than native IGF-I, which reverses the ordering seen in lines that do secrete them. [1]
Recombinant IGFBP-3 suppressed proliferation stimulated by native IGF-I and by the analogue alike, but suppressed differentiation only when native IGF-I was the stimulus, separating a binding protein dependent effect from a binding protein independent one. [2][3]
Analysis of a vial obtained outside regulated supply identified the analogue carrying a hexahistidine tag at the C-terminus through a Leu-Glu linker, a purification tag normally removed or left only on material made for biochemical study. [4]

Identity and structure

Construct: An IGF-I sequence preceded by the first eleven amino acids of methionyl porcine growth hormone plus Val-Asn, with Glu3 of the human IGF-I sequence replaced by arginine [1]
Not native IGF-I: Native IGF-I, the truncated des(1-3) analogue, the Long [Gly3] analogue and this analogue behaved differently in the same assays, so papers on native IGF-I describe a different material [1][5]
Binding protein interaction: Binds poorly to the IGF binding proteins, and has a similar receptor affinity to native IGF-I with much lower affinity for IGFBP-1 in the cited hypoxia work [6][7]
Species variants: A chicken version of the same analogue design exists and behaved differently from chicken IGF-I in avian muscle cells, so the species of the IGF-I sequence matters as well as the modification [8]
Tagged material found in supply: A vial examined in the cited analytical work contained the analogue with a hexahistidine tag attached to the C-terminus by the linker residues Leu-Glu [4]
Form as supplied: Sterile lyophilized powder

Mechanism as studied

The design logic is stated in the original construct paper. Three fusion peptides were compared, differing only at position 3, and their relative potency ordering followed whether the cell line secreted binding proteins into the medium. In lines that did, the arginine analogue and des(1-3)IGF-I led; in chicken embryo fibroblasts, which secrete no detectable binding proteins, the analogue fell below native IGF-I. The authors conclude that the raised potency comes from reduced binding protein interaction. [1]

Receptor level work supports that reading. IGFBP-3 inhibited receptor phosphorylation induced by native IGF-I, IGF-II, des(1-3)IGF-I and this analogue over a similar concentration range, and cross-linking found no direct interaction between IGFBP-3 and the receptor, so the effect is sequestration of the ligand in the extracellular medium rather than an action at the receptor. [5]

Two later systems isolate the same variable. In L6 myogenic cells, binding protein driven suppression of proliferation applied to both ligands while suppression of differentiation applied only to native IGF-I. In hypoxic HepG2 cultures, where phosphorylated IGFBP-1 rose, native IGF-I lost receptor and IRS-1 phosphorylation and proliferation while the analogue kept them. [2][7]

Research findings

In vitro

System: L6 rat myoblasts, H35 hepatoma cells and chicken embryo fibroblasts, comparing Long IGF-I, Long [Gly3]-IGF-I, Long [Arg3]-IGF-I, native IGF-I and des(1-3)IGF-I produced in an E. coli expression system
Measured: Protein and DNA synthesis, inhibition of protein breakdown, relative biological potency in lines that do and do not secrete IGF binding proteins, and receptor and binding protein association
Reported: All analogues were more potent than native IGF-I in L6 myoblasts for protein and DNA synthesis and for inhibiting protein breakdown, and the ordering in binding protein secreting lines was Long [Arg3]-IGF-I and des(1-3)IGF-I above Long [Gly3]-IGF-I above Long IGF-I above native IGF-I. In chicken embryo fibroblasts, which secrete no detectable binding proteins, Long [Arg3]-IGF-I was less potent than native IGF-I. [1]

Analytical

System: A vial obtained outside regulated supply, with the contents isolated by immunoaffinity purification
Measured: Identity of the protein present by nano-UPLC with high resolution and high accuracy mass spectrometry of the intact and trypsinated substance, and by enzyme-linked immunosorbent assay
Reported: Mass spectra characterised the protein as the Long-R3 analogue of IGF-I with a hexahistidine tag attached to the C-terminus by the linker amino acids Leu-Glu, a form the authors describe as usually produced for biochemical studies rather than as a supplied product. [4]

In vitro

System: L6 myogenic cells, a line that produces no detectable IGFBP-3 of its own, with recombinant porcine IGFBP-3 supplied exogenously, comparing native IGF-I against the analogue
Measured: Proliferation and differentiation stimulated by each ligand with and without recombinant IGFBP-3, and phosphosmad-2 levels
Reported: IGFBP-3 suppressed proliferation stimulated by native IGF-I and by the analogue alike and did so without raising phosphosmad-2, indicating both IGF dependent and IGF independent mechanisms. It suppressed differentiation stimulated by native IGF-I but not differentiation stimulated by the analogue. [2]

In vitro

System: L6 myogenic cells stably transfected to express porcine IGFBP-3 constitutively, against mock transfected cells carrying the empty vector
Measured: IGFBP-4 and IGFBP-5 expression, proliferation and differentiation stimulated by native IGF-I and by the analogue after immunoneutralisation of IGFBP-3, and immunohistochemical localisation of the binding protein
Reported: Immunoneutralising IGFBP-3 raised proliferation stimulated by native IGF-I by 58 percent and by the analogue by 33 percent. It raised IGF-I stimulated differentiation by 21 percent and had no effect on differentiation stimulated by the analogue, matching the pattern seen with exogenous binding protein. [3]

In vitro

System: Cell monolayers exposed to native IGF-I, IGF-II, des(1-3)IGF-I, this analogue, the QAYL analogue or insulin, with intact IGFBP-3 or its 1-97 proteolytic fragment
Measured: IGF-I receptor phosphorylation under each ligand and binding protein combination, and direct interaction between IGFBP-3 and the receptor by monolayer cross-linking with radiolabelled binding protein
Reported: Intact IGFBP-3 inhibited receptor phosphorylation induced by native IGF-I, IGF-II, des(1-3)IGF-I and this analogue over a similar concentration range but not that induced by the QAYL analogue. The 1-97 fragment inhibited only the native IGF-I response, and cross-linking showed no direct interaction of the binding protein with the receptor. [5]

In vitro

System: Turkey satellite cells and embryonic myoblasts in serum-free medium, testing the chicken version of the LR3 analogue against chicken IGF-I, human and chicken IGF-II and two further analogues
Measured: Proliferation under each ligand and competition of each ligand against radiolabelled human IGF-I for binding to the cells
Reported: The chicken LR3 analogue was significantly less active toward satellite cells and embryonic myoblasts than chicken IGF-I, and it competed less well against radiolabelled IGF-I for binding. The authors conclude that binding proteins have little effect in these cell types in serum-free medium and that removing binding protein interaction can also alter receptor binding affinity. [8]

In vitro

System: HepG2 cell cultures under low oxygen conditions, a line that secretes IGFBP-1 and expresses IGF-I receptors, comparing native IGF-I against the analogue
Measured: IGFBP-1 concentration and phosphorylation state by native and denaturing PAGE with immunoblotting, IGF-I receptor and IRS-1 phosphorylation, and cell proliferation under each ligand
Reported: Low oxygen raised total IGFBP-1 and made the highly phosphorylated isoforms dominant, and attenuated receptor and IRS-1 phosphorylation and proliferation under native IGF-I. Under the analogue, which has similar receptor affinity but much lower affinity for IGFBP-1, neither the phosphorylation nor the proliferation was inhibited. [7]

Preclinical in vivo

System: Preweaning and adult rats given radiolabelled native IGF-I or the radiolabelled analogue
Measured: Radiolabel retained in blood at five and ten minutes and the labelled peptide present per gram of gastrointestinal tissue, compared across the two ligands and the two ages
Reported: Blood levels of labelled native IGF-I exceeded those of the labelled analogue at both time points, consistent with slower clearance of the native peptide. Labelled analogue per gram of gastrointestinal tissue was 37 to 50 percent above labelled native IGF-I, with a ratio of about two to one in both age groups, which the authors say does not explain the potency difference seen in the developing intestine. [6]

Order IGF-1 LR3 with the certificate for the lot that ships

Handling for in-vitro work

Folding in cited production work: Purified fusion peptides were folded from the reduced and denatured state, and the hydrophobic N-terminal extension appeared to assist correct folding compared with normal-length IGF proteins [1]
Medium in cited work: Comparisons were run in serum-free medium or in lines chosen for their binding protein secretion, because binding proteins in the medium change the measured potency [8][1]
Storage: Lyophilized at -20 °C, dark and dry; reconstituted aliquots kept cold and used promptly

Open questions

Potency of this analogue relative to native IGF-I reverses with the binding protein content of the assay, so a result cannot be quoted without the medium and cell line it was measured in.
One cited paper used the chicken version of the analogue and native chicken IGF-I, so species of the underlying sequence is a separate identity question from the modification.
A vial examined in the cited analytical work carried a hexahistidine purification tag, so the presence or absence of a tag on a supplied lot is not settled by the product name.
The cited work does not establish a receptor level difference between this analogue and native IGF-I beyond their binding protein interactions.

Clinical literature on insulin-like growth factor I concerns the native protein in finished formulations rather than this analogue, and is out of scope for this profile.

Lot records

Check the record for the exact material you order. A published paper and a batch certificate answer different questions.

RV-24-0035-2 ↗IGF-1 LR3 · 99.60% HPLC
2026-09-22
RV-24-0035-1 ↗IGF-1 LR3 · 99.60% HPLC
2026-09-16

Read a certificate of analysis ↗

References

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.
PubMed 1378742 · doi:10.1677/jme.0.0080213
Xi G, Kamanga-Sollo E, Pampusch MS, et al. Effect of recombinant porcine IGFBP-3 on IGF-I and long-R3-IGF-I-stimulated proliferation and differentiation of L6 myogenic cells. Journal of cellular physiology. 2004.
PubMed 15254966 · doi:10.1002/jcp.20068
Xi G, Kamanga-Sollo E, Hathaway MR, et al. Effect of constitutive expression of porcine IGFBP-3 on proliferation and differentiation of L6 myogenic cells. Domestic animal endocrinology. 2006.
PubMed 16233971 · doi:10.1016/j.domaniend.2005.09.008
Kohler M, Thomas A, Walpurgis K, et al. Detection of His-tagged Long-R³-IGF-I in a black market product. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. 2010.
PubMed 20675162 · doi:10.1016/j.ghir.2010.07.001
Devi GR, Graham DL, Oh Y, et al. Effect of IGFBP-3 on IGF- and IGF-analogue-induced insulin-like growth factor-I receptor (IGFIR) signalling. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. 2001.
PubMed 11735239 · doi:10.1054/ghir.2001.0231
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.
PubMed 12697696 · doi:10.1210/en.2002-220643
Tsunawaki T, Sakai K, Momomura M, et al. Hypoxia alters phosphorylation status of insulin-like growth factor (IGF)-binding protein-1 and attenuates biological activities of IGF-I in HepG2 cell cultures. The journal of obstetrics and gynaecology research. 2013.
PubMed 23815140 · doi:10.1111/jog.12078
Pesall JE, McFarland DC, McMurtry JP, et al. The effect of insulin-like growth factor analogs on turkey satellite cell and embryonic myoblast proliferation. Poultry science. 2001.
PubMed 11469659 · doi:10.1093/ps/80.7.944

Publication records fetched from PubMed on 2026-09-20. Profile text reviewed 2026-09-20.