Long R3 IGF-1IGF-1 LR3
IGF-1 re-engineered to slip past its binding proteins — free, unbuffered signal at the receptor.
Native IGF-1 spends its life held; this is the version engineered to travel free. A signal's reach is set as much by what carries it as by what it says.
Identity
- Class
- 83-aa IGF-1 analog (Arg³ substitution + 13-aa N-terminal extension)
- Source
- Synthetic analog of IGF-1
- Receptor
- IGF-1 receptor (IGF-1R), a receptor tyrosine kinase
Key properties
Evidence floorClinicalREF1CLIN1Approximate values for the native hormone; engineered analogs are often deliberately larger and far longer-acting. Each figure carries its own provenance tier, and the floor is the weakest of them - the Standard.
Mechanism
Native IGF-1 travels almost entirely bound to IGF-binding proteins, which buffer its activity and clear it within minutes. LR3 carries two changes — arginine for glutamate at position 3, and a 13-residue N-terminal extension — that together cripple that binding. The analog stays free, delivers the same message to IGF-1R with far more of it reaching the receptor, and — in preclinical and cell-culture work — outlasts free native IGF-1.
Reference notes
- Both modifications serve one goal — escape the IGFBPs. Free and unbuffered, LR3 is markedly more potent than native IGF-1, and is a standard cell-culture reagent for exactly that reason.
- A widely repeated half-life claim is backwards: for native IGF-1, binding to IGFBP-3 and the acid-labile subunit is what extends circulating half-life (~12–16 h bound vs ~10–15 min free), so evading the IGFBPs should shorten persistence, not lengthen it. Any longer-lasting activity is attributed to protease resistance and in-vitro availability, and no human PK for LR3 has been published.
- The unbuffered, systemic exposure is the point and the problem: sustained IGF-1R activation is mitogenic, the core safety concern that keeps it research-only.
- des(1-3)IGF-1, which instead deletes the first three residues, is the sister analog built on the same idea of dodging the binding proteins.
Common questions
- What is Long R3 IGF-1 (IGF-1 LR3)?
- IGF-1 re-engineered to slip past its binding proteins — free, unbuffered signal at the receptor. Structurally it is 83-aa IGF-1 analog (Arg³ substitution + 13-aa N-terminal extension).
- How does IGF-1 LR3 work?
- Native IGF-1 travels almost entirely bound to IGF-binding proteins, which buffer its activity and clear it within minutes. LR3 carries two changes — arginine for glutamate at position 3, and a 13-residue N-terminal extension — that together cripple that binding. The analog stays free, delivers the same message to IGF-1R with far more of it reaching the receptor, and — in preclinical and cell-culture work — outlasts free native IGF-1.
- How strong is the evidence for IGF-1 LR3?
- PeptideHormone grades IGF-1 LR3 at the "Preclinical" evidence tier — the evidence is largely animal or in-vitro, with human data thin or absent. It is catalogued as an engineered analog built on an endogenous hormone, and the tier is an editorial judgment about the public literature that can change as the science does.
- What is the half-life of IGF-1 LR3?
- The reported circulating half-life of IGF-1 LR3 is Hours in vitro (no human PK published).
Selected literature
Curated peer-reviewed reviews, sourced from PubMed. Selected for relevance, not exhaustive — open any entry on PubMed for the full record and its primary citations.
- 1.IGF-binding proteins · Journal of molecular endocrinology, 2018 · PMID 29255001
- 2.Insulin-like growth factor binding proteins 4-6 · Best practice & research. Clinical endocrinology & metabolism, 2015 · PMID 26522456
- 3.Implications of Insulin-like Growth Factor 1 Receptor Activation in Lung Cancer · The Malaysian journal of medical sciences : MJMS, 2016 · PMID 27418865
External references
IGF-1 LR3 in the public knowledge graph — the same entity resolved across the authoritative chemistry and protein databases.