IGF-1 LR3

Long R3 IGF-1, LR3-IGF-I, Long arginine-3 insulin-like growth factor-1, LONG R3 IGF-I (reagent name)

Growth hormone axis

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Summary

Class: Recombinant 83-amino-acid analogue of human IGF-1: the native 70-amino-acid sequence with glutamate-3 replaced by arginine, plus a 13-amino-acid N-terminal extension
Mechanism: Activates the IGF-1 receptor like native IGF-1 but barely binds the IGF-binding proteins that normally buffer it, so more stays free and active for longer
Routes studied: Cell culture (its designed use); subcutaneous and infusion in rats; subcutaneous and intramuscular (community)
Dose range reported: Rat studies: roughly 0.3–3 mg/kg/day by infusion or injection. Community: 20–50 µg per day subcutaneous or intramuscular, typically in 4-week cycles. No human dose has ever been studied
Half-life: Native IGF-1 free in plasma: ~10–20 minutes; bound to IGFBP-3, ~12–15 hours. LR3: longer than free IGF-1 in animals; community cites 20–30 hours, which has not been established in humans †
Storage: Lyophilised: refrigerate or freeze, protect from light. Reconstituted: refrigerate; a protein of this size is more fragile than small peptides — avoid shaking and freeze–thaw
Regulatory status: Not approved for human use anywhere; sold legitimately only as a laboratory reagent

Doses are as reported in studies or by the community — never recommendations.

1What it is

IGF-1 (insulin-like growth factor-1) is the natural hormone that carries most of growth hormone's growth-promoting signal. The liver makes it in response to GH, and muscle, bone and other tissues make it locally. In the blood, almost all IGF-1 is bound to carrier proteins (IGFBPs, mainly IGFBP-3), which keep it inactive until released.

IGF-1 LR3 is not natural. It was engineered in Adelaide, Australia, in the early 1990s by GroPep (Francis 1992) as a cell-culture additive: a version of IGF-1 that the binding proteins in culture medium would not soak up, so that smaller amounts would keep cells growing. It is widely used today in biomanufacturing to grow cell lines that make antibodies and other drugs. It was never designed or tested as a medicine.

The approved medicine in this space is native recombinant IGF-1 (mecasermin, brand Increlex), used in children with severe primary IGF-1 deficiency. Its safety record is the best guide to what IGF-1 receptor stimulation does in humans. IGF-1 LR3's community reputation as a "longer-acting, stronger IGF-1" follows directly from its design, but no human data exist.

2How it's thought to work

Receptor. binds the IGF-1 receptor with affinity similar to native IGF-1, activating the PI3K/Akt/mTOR pathway (protein synthesis, cell survival) and MAPK (proliferation).

Binding proteins. the arginine-3 substitution and N-terminal extension reduce affinity for IGFBPs by orders of magnitude, so a given dose produces far more free, receptor-available IGF-1 than native IGF-1 would.

Muscle. IGF-1 signalling stimulates satellite-cell proliferation and protein synthesis and inhibits breakdown; local IGF-1 overexpression enlarges rodent muscle.

Insulin receptor. IGF-1 has weak insulin-receptor activity and strong glucose-lowering effects at pharmacological doses; with the binding-protein buffer removed, LR3 is expected to lower glucose more sharply.

Native IGF-1 is mostly held by binding proteins (left). LR3, with its extended tail, barely binds them, so more reaches the IGF-1 receptor on muscle.Schematic — not to scale

3What the research shows

Graded D/C

Potency relative to IGF-1

The defining paper showed LR3 to be 2–3-fold more potent than IGF-1 in cell proliferation assays and more potent in rats, attributed to reduced IGFBP binding (Francis 1992, J Mol Endocrinol). [1]

Anabolic effects in rats

In catabolic rat models (dexamethasone treatment, gut resection, diabetes, nitrogen restriction), LR3 infusion improved nitrogen retention, weight gain and muscle protein, generally more than native IGF-1 at the same dose (Tomas 1993, Biochem J, and related papers from the same group). Healthy adult animals gain less. [2]

Not gradednone

Human data

No clinical trial of IGF-1 LR3 in humans has been published. Everything below about human effects is inferred from native IGF-1.

Graded A/B

Native IGF-1 in humans (context)

Short infusions of recombinant IGF-1 in healthy adults caused hypoglycaemia and suppressed insulin (Guler 1987, NEJM). Long-term mecasermin in children with IGF-1 deficiency improves growth but with hypoglycaemia, lipohypertrophy at injection sites, tonsillar and adenoid enlargement, intracranial hypertension and coarsening of facial features in some (Chernausek 2007, J Clin Endocrinol Metab). Observational studies associate higher circulating IGF-1 with modestly increased risk of several cancers (Renehan 2004, Lancet). [3][4][5]

4Reported side effects and interactions

Literature-reported

No human data for LR3. From native IGF-1: hypoglycaemia (the dominant acute risk — IGF-1 lowers glucose directly), headache, injection-site fat accumulation, jaw and facial changes, tonsillar hypertrophy, intracranial hypertension, and a theoretical and epidemiological link between IGF-1 exposure and cancer risk.

Community-reported

hypoglycaemia symptoms (shakiness, sweating, hunger) especially if dosed without food, injection-site lipohypertrophy, headache, joint aches, water retention, and — anecdotally — gut and organ "growth" concerns that cannot be verified.

Theoretical. because LR3 escapes binding-protein buffering, its glucose-lowering and mitogenic effects are expected to be sharper than native IGF-1; growth of any existing tumour; acromegaly-like changes with sustained high exposure; suppression of endogenous GH via feedback.

Interactions. additive hypoglycaemia with insulin, sulfonylureas, GLP-1 or fasting; GH raise endogenous IGF-1 on top of it; glucocorticoids counteract.

Markers researchers commonly monitor

Marker	Why it's watched
Fasting and post-dose glucose	hypoglycaemia is the main acute risk; the one marker with immediate practical relevance.
IGF-1	standard immunoassays may under- or over-detect LR3 depending on antibody epitopes, so a measured IGF-1 may not reflect true exposure †; a fall in native IGF-1 can indicate GH-axis suppression.
IGFBP-3	tends to fall when GH is suppressed.
Growth hormone	suppressed by IGF-1 feedback.
HbA1c and lipids	longer-term metabolic drift.
Clinical: injection-site tissue changes, headache or visual symptoms (intracranial hypertension), tonsillar enlargement

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Usually supplied as 1 mg vials, often with instructions to in dilute acetic acid rather than because the protein is more stable at low pH; some sources use sterile water. Doses are in tens of micrograms, so dilution errors are easy — use the calculator and double-check units. Avoid shaking.

Open in calculator, pre-loaded →

6Commonly studied alongside

In the community, GH secretagogues, GH itself and anabolic steroids; none of these combinations has been studied. In cell culture it is combined with insulin and transferrin as a serum-free medium supplement.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved; not eligible for compounding. Mecasermin (native IGF-1) is approved for severe primary IGF-1 deficiency only
European Union	Not authorised; mecasermin authorised for the same narrow indication
United Kingdom	Not licensed
Australia	Not approved; IGF-1 and analogues are prescription-only (Schedule 4) †
South Africa	Not registered
Sport (WADA)	Prohibited (S2 — IGF-1 and its analogues are explicitly named)

8Open questions

Pharmacokinetics in humans — entirely uncharacterised.
Whether IGFBP-independent IGF-1 exposure increases cancer risk beyond what high native IGF-1 does.
Whether locally injected LR3 has any site-specific effect, as community practice assumes, or acts purely systemically.

9References

1Francis GL et al. (1992). 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. PubMed · DOI
2Tomas FM et al. (1993). Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic in dexamethasone-treated rats. Biochem J. PubMed · DOI
3Guler HP, Zapf J, Froesch ER (1987). Short-term metabolic effects of recombinant human insulin-like growth factor I in healthy adults. N Engl J Med. PubMed · DOI
4Chernausek SD et al. (2007). 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. PubMed · DOI
5Renehan AG et al. (2004). Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet. PubMed · DOI
6Laron Z (2001). Insulin-like growth factor 1 (IGF-1): a growth hormone. Mol Pathol. PubMed · DOI

† Being confirmed by our reviewers against current sources.

10Community

forum threads →

community protocols include this →

Threads and protocols are visible to members. Joining is free.

Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

25 Oct 2026Profile published — awaiting medical review

Licensed CC BY-NC-SA 4.0. Found an error? Report it · Editorial standards — corrections are logged here.