Bottom line
IGF-1 LR3 (Long R3 IGF-1) is a recombinant analog of human IGF-1 with two modifications: (1) a Glu3→Arg substitution, and (2) a 13-amino-acid N-terminal extension derived from methionyl porcine growth hormone. These modifications reduce binding to IGF-binding proteins (IGFBPs) by >1000-fold, creating a research tool for cell culture where IGFBP interference is unwanted. It is marketed in the research chemical space as a "longer-acting IGF-1," but it has never been studied in human clinical trials and is not approved for any human use. It is a distinct compound from the approved drug mecasermin.
Identity and composition
| Field | Verified information |
|---|---|
| Preferred name | Long R3 IGF-1 |
| Key aliases | IGF-1 LR3, LR3 IGF-1, Long Arg3 IGF-1 |
| Molecular/sequence identity | Recombinant 83-amino-acid protein = 13-aa N-terminal extension (derived from porcine GH) + full-length human IGF-1 (70 aa) sequence with Arg substituting Glu at position 3 of the mature sequence |
| Modifications/form | N-terminal 13-aa extension + Glu3→Arg substitution; reduced IGFBP affinity |
| Stable identifiers | MW ~9.1 kDa; Sigma-Aldrich I1146/I1271; R&D Systems 8335D-GMP |
| Identity caveats | IG is NOT the same as mecasermin (Increlex), which is full-length unmodified rhIGF-1. The "R3" refers to the arginine substitution at position 3. The term "Long" refers to the N-terminal extension. Vendor marketing often misrepresents this cell-culture reagent as a "research peptide" with implied human applications. |
Development and approval status
| Jurisdiction | Status and indication | Product/source | As of |
|---|---|---|---|
| US (FDA) | No human clinical use; sold as cell culture reagent / research chemical | — | 2026-08-06 |
| Registers reviewed | No FDA-approved product or EMA-authorized medicine identified; status elsewhere requires a current national-register check | — | 2026-08-06 |
Mechanism and pharmacology
IGF-1 LR3 binds the IGF-1 receptor with affinity comparable to native IGF-1 but has dramatically reduced affinity for IGFBPs (Kd >1 µM vs nM for native IGF-1). This results in greater free peptide availability at the receptor. The modifications also confer enhanced proteolytic stability. In cell culture, the reported half-life of free IGF-1 LR3 is longer than native IGF-1, but in vivo pharmacokinetics in humans have not been studied.
Evidence by claim
| Claim/indication | Stage | Grade | Best human evidence | Main result | Important limitations |
|---|---|---|---|---|---|
| Cell culture growth supplement | Reagent | N/A | Extensive in vitro use | Maintains IGF-1R activation in serum-supplemented media | Cell culture only; no human relevance |
| Muscle growth (IGF-1R activation) | Preclinical | D | Rodent studies from 1990s | Anabolic effects in several rodent models | Animal data only; not translatable to humans without human studies |
| Anabolic/body composition | Marketing | E | No controlled human studies | No adequate evidence | No human data of any kind |
| Human therapeutic use | None | X | No clinical trials | Never studied in humans | No safety or efficacy data in humans |
Key studies
| Study | Design/population | Exposure studied | Endpoints and result | Limitations |
|---|---|---|---|---|
| Tomas et al., J Endocrinol 1993 | Rat pharmacology | SC IGF-1 LR3 | Anabolic effect; reduced IGFBP binding | Rodent; no human |
| Francis et al., J Mol Endocrinol 1992 | Structure-activity | In vitro | Reduced IGFBP binding characterized | In vitro only |
| Voorhamme & Yandell, Mol Biotechnol 2006 | Reagent characterization | In vitro | >100-fold reduced IGFBP affinity vs wild-type | Technical reagent paper |
Dose and administration evidence
Approved labeled regimen
Not applicable.
Studied regimens (not recommendations)
No established or recommended human dose. No human study has established a dose for this compound.
What is not established
No human pharmacokinetics
No human safety data
No human efficacy data
The marketed in vivo "dosing protocols" are community practice without clinical support
Half-life in humans is unknown
Safety
No human safety data exist. Theoretical risks from IGF-1 receptor activation include hypoglycemia (IGF-1 has weak insulin-like activity), mitogenic effects promoting neoplasia, and acromegalic effects if systemic levels are elevated. Research-grade material from unregulated suppliers may have degradation products with unknown bioactivity.
Unknowns and product-quality risks
All safety parameters in humans are unknown. The compound is a cell culture reagent being sold for unapproved human use. Identity and purity of gray-market material are not regulated. PEGylation or other claims of extended half-life beyond the intrinsic modification are often unsubstantiated.
Interactions and special populations
No data exist.
Regulatory, compounding, and sport notes
IGF-1 LR3 falls within WADA S2 prohibition (IGF-1 and its analogs). The approved drug mecasermin is the only IGF-1 medicine; modified analogues are unapproved.
Evidence gaps
No human study of any kind
No pharmacokinetic data in humans
No toxicology data
No efficacy data in humans
No data on tissue distribution or IGFBP interaction in vivo in humans
Search notes
Databases and registries: PubMed, PubChem, Sigma-Aldrich, FDA Drugs@FDA
Search terms: "IGF-1 LR3", "Long R3 IGF-1", "LR3 IGF-1", "Long Arg3 IGF-1"
Last searched: 2026-08-06
Inclusion emphasis: Primary peer-reviewed data; manufacturer specifications for cell culture use
Sources
Tomas FM et al. The anabolic effects of insulin-like growth factor-I (IGF-I) and long R3 IGF-I in rats. J Endocrinol. 1993;137(3):413-421. PMID 8371075. https://pubmed.ncbi.nlm.nih.gov/8371075/
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. PMID 1371669. https://pubmed.ncbi.nlm.nih.gov/1371669/
Voorhamme D, Yandell CA. LONG R3 IGF-I as a more potent alternative to insulin in serum-free culture of HEK293 cells. Mol Biotechnol. 2006;34(2):201-204. PMID 17172665. https://pubmed.ncbi.nlm.nih.gov/17172665/
Repligen. LONG R3 IGF-I Cell Culture Supplement. https://www.repligen.com/products/cell-culture-supplements/long-r3-igf-i
WADA Prohibited List 2026. https://www.wada-ama.org/en/prohibited-list