Description

IGF-1 LR3 – Advanced Biochemical Mechanism Profile

(Long Arg3 Insulin-Like Growth Factor-1; IGF-1R Agonist; Prolonged Half-Life Peptide Analog)

IGF-1 LR3 is an engineered analogue of human IGF-1, modified at the third amino acid (Arg substitution) and extended 13 amino acids at the N-terminus.
These changes markedly reduce binding to IGF Binding Proteins (IGFBPs), resulting in prolonged bioavailability and sustained IGF-1 receptor (IGF-1R) signaling in vitro.

✅ 1. Primary Receptor Target

IGF-1 Receptor (IGF-1R)

• Class: Tyrosine kinase receptor

• Mechanism: Ligand binding → receptor dimerization → autophosphorylation

• Cell types: Muscle, liver, neuronal, connective tissue, endothelial, and stem-cell models

Activation sequence:

1. IGF-1 LR3 binds extracellular α-subunits

2. Receptor dimerizes

3. β-subunit tyrosine autophosphorylation

4. Recruitment of IRS-1/2, Shc, and PI3K signaling complexes

✅ 2. Major Signaling Pathways

✅ A. IRS-1/2 → PI3K → Akt / PKB Pathway

Primary metabolic and growth pathway.

• IRS-1 phosphorylation recruits PI3K

• PI3K converts PIP2 → PIP3

• Akt is phosphorylated by PDK1

• Akt activates mTOR, p70S6K, 4E-BP1 → protein synthesis

Gene targets commonly monitored:

• Myogenic factors: MYOD1, MYOG

• Protein translation: RPL, RPS, EIF4EBP1

• Mitochondrial biogenesis: PGC-1α

• Anti-apoptotic genes: BCL2, MCL1

✅ B. Ras → Raf → MEK → ERK1/2 MAPK Pathway

Mitogenic and proliferative signaling.

• IRS-1 and Shc recruit Grb2/SOS

• Ras-GTP activates Raf

• Raf → MEK1/2 → ERK1/2

• ERK translocates to nucleus → induces transcription

MAPK-responsive genes:

• FOS, JUN, EGR1

• Cyclins (CCND1, CCNE1) for cell-cycle progression

✅ C. JAK/STAT Crosstalk

Some cell systems demonstrate:

• STAT3/STAT5 phosphorylation

• Gene activation associated with growth and differentiation

✅ 3. Second Messengers, Enzymes & Intermediate Proteins

✅ 4. Gene-Level Outputs (Frequently Measured in Research)

✅ 5. Why LR3 Has Prolonged Activity

• Reduced affinity for IGF Binding Proteins (IGFBP-1 to IGFBP-6)

• Greater fraction remains free in the extracellular compartment

• Longer receptor availability → extended PI3K/Akt and MAPK activation

Research-Only Use Classification

IGF-1 LR3 is supplied solely for controlled in-vitro laboratory research.
It is not approved for human or animal consumption, injection, ingestion, therapeutic application, or diagnostic use.