In rats, LR3-IGF-I (which binds IGFBP-3 about 1000-fold less avidly than IGF-I) was about 6-fold more potent than IGF-I for growth but was removed from plasma much more rapidly than IGF-I, circulating largely as free peptide.
rats
IGF-1 LR3
Not available
Growth
IGF-1 LR3
An unapproved lab-made analog of IGF-1
Not FDA-approved · not available for sale or prescriptionOverview.
IGF-1 LR3 has never been tested in a human clinical trial and has no approved medical use. It is a laboratory-research recombinant analog of human insulin-like growth factor 1, engineered with an Arg-for-Glu substitution at position 3 and a 13-amino-acid N-terminal extension ('Long'). These changes sharply reduce its binding to IGF-binding proteins, so more of it is free and biologically active; in animals it is several-fold more potent than native IGF-1 even though it is cleared from the blood faster. It must not be confused with mecasermin (Increlex), the FDA-approved recombinant native-sequence human IGF-1 product.
Also known as Long R3 IGF-1 · LR3-IGF-I · Long [Arg3]-IGF-I
The molecule, decoded.
- Sequence
-
MFPAMPLSSLFVNGPRTLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA
- Length
- 83 residues
- Molecular weight
- 9,111.5 g/mol
- Formula
- C400H619N111O115S9
- CAS number
- 143045-27-6
- Half-life
- Not established in humans (cleared faster than native IGF-1 in rats)
- Routes studied
- subcutaneous/intramuscular injection (animal and in vitro research only; no human route has been studied in a registered trial)
- Modifications
- 13-residue N-terminal extension plus Glu3->Arg3 substitution vs. native human IGF-1; not separately indexed as its own PubChem compound record
How it works.
Retains full agonist activity at the type 1 IGF receptor (IGF-1R), activating PI3K/Akt and Ras/MAPK signaling to drive protein synthesis and cell proliferation, while its reduced affinity for IGFBP-1 through IGFBP-6 leaves more of the circulating molecule free and receptor-available, unlike native IGF-1, most of which is bound and buffered by IGFBPs.
Evidence · Lab and animal studies only
What the research shows
In pigs, LR3-IGF-I and other IGF-I variants that bind IGFBPs poorly were 2-3-fold more potent than native IGF-I at lowering blood glucose and produced longer-lasting hypoglycaemia (about 2-fold greater cumulative effect at equipotent doses), despite faster clearance from the circulation.
pigs (other variants also in marmosets)
The original 'Long [Arg3]-IGF-I' fusion analog was more potent than IGF-I in cells that secrete IGF-binding proteins (L6 myoblasts), consistent with its much weaker IGFBP binding, but was less potent than IGF-I in chicken embryo fibroblasts that secrete no IGFBPs.
n/a
Mecasermin (recombinant native-sequence IGF-1), the FDA-approved comparator, lists hypoglycemia first among its warnings (it has no boxed warning); in its clinical trials 42% of subjects had hypoglycemia at least once, 5 had severe hypoglycemia and 4 had hypoglycemic seizures or loss of consciousness.
children with severe primary IGF-1 deficiency
IGF-1 LR3 has never been evaluated in a registered human clinical trial for any indication, including muscle growth or body-composition endpoints; no human safety database exists.
n/a
What to know first.
Based on: lab and animal studies only; human risks are inferred from native IGF-1 (mecasermin) data, not from studies of IGF-1 LR3.
Reported side effects
- not established in humans (no human trials)
Cautions
- hypoglycemia is the primary mechanistic safety concern: in pigs LR3-IGF-I was 2-3x more potent than IGF-I at lowering glucose, with longer-lasting effect, and native-sequence mecasermin's label warns of severe hypoglycemia; there are no human data for IGF-1 LR3
- no human safety, toxicology, immunogenicity or long-term data exist
- theoretical proliferative/oncogenic risk from sustained, unbuffered IGF-1R activation (mecasermin is contraindicated with malignant neoplasia), not directly studied
Checked 2026-09
Where it stands.
Not FDA-approved · not available for sale or prescription. IGF-1 LR3 is not FDA-approved and is not available for sale or prescription. We profile it because people ask about it.
- FDA
- not approved; no clinical development program exists. The related but distinct molecule mecasermin (native-sequence recombinant human IGF-1, brand Increlex) is FDA-approved (2005) for severe primary IGF-1 deficiency -- IGF-1 LR3 is not mecasermin and is not covered by that approval.
- Compounding
- Not eligible for 503A compounding: it has no USP monograph, is not a component of an FDA-approved drug, is not on the 503A Bulks List and is in no 503A category. As a modified, non-native protein, it does not qualify for compounding under the mecasermin approval either.
- Sport (WADA)
- Prohibited at all times under S2 of the WADA Prohibited List, which names 'insulin-like growth factor-1 (IGF-1, mecasermin) and its analogues' -- IGF-1 LR3 falls within 'analogues' under this wording even though it is not separately named.
- Enforcement
- FDA warning letter to Tailor Made Compounding (Apr 1, 2020) cited compounding with IGF1-LR3, which FDA said is not eligible for 503A (no USP monograph, not a component of an approved drug, not on the 503A bulks list)