IGF1-LR3 1mg vial

NOT FOR HUMAN CONSUMPTION

IGF-1 LR3 is a recombinant analog of human insulin-like growth factor-1 (IGF-1) in which an arginine replaces the native third–position glutamic acid and a 13-amino-acid extension is added to the N-terminus.
These changes (i) reduce binding to IGF-binding proteins (IGFBPs) by >90 %, (ii) extend the plasma half-life from minutes to hours, and (iii) enhance receptor potency 2- to 3-fold relative to native IGF-1.
Originally engineered for serum-free biomanufacturing, IGF-1 LR3 is now being evaluated for metabolic disease, regenerative medicine, and geroscience applications. Repligen

2. Molecular Mechanism of Action

2.1 Receptor Pharmacodynamics

IGF-1 LR3 binds the IGF-1 receptor (IGF-1R) with an affinity comparable to native IGF-1, triggering PI3K–Akt and Ras–MAPK cascades that govern protein synthesis, cell survival, glucose uptake, and mitogenesis.
Because it dissociates poorly from IGFBPs, native IGF-1 is locally buffered; in contrast, IGF-1 LR3 circulates largely free, producing a higher receptor area-under-curve and broader tissue distribution. cellsciences.com

2.2 Down-stream Biology

Key downstream effects include:

3. Pharmacokinetics

• Plasma half-life: 6–8 h (rat), estimated 8–12 h in humans (vs ~20 min for IGF-1).

• Distribution: Limited BBB permeability but detectable CNS levels after high systemic or intranasal dosing. PubMed

• Clearance: Primarily hepatic/renal proteolysis; minimal IGFBP sequestration accelerates renal filtration at supraphysiologic doses.

4. Pre-clinical and Translational Evidence

4.1 Metabolic Disease

In diet-induced obese mice, IGF-1 LR3 improves insulin sensitivity and lowers fasting glucose without causing hypoglycaemia—likely via Akt-driven GLUT4 translocation rather than insulin receptor cross-activation. (White et al., 2025) journals.physiology.org

4.2 Skeletal Muscle & Regeneration

Rodent studies show:

• 20–40 µg kg⁻¹ day⁻¹ increases gastrocnemius fibre cross-section by ~15 % within 21 days.

• Accelerated satellite‐cell activation and collagen deposition after crush injury, shortening return-to-force time by 25 %.

4.3 Neuroprotection

Intranasal IGF-1 LR3 (50 µg day⁻¹ for 4 wks) reduced cortical amyloid load in 5xFAD mice, though cognition was not rescued, highlighting transport but limited functional translation. PubMed

4.4 Fetal Growth Restriction

A late-gestation ovine model showed no catch-up growth after one-week infusion, underscoring gestational timing and IGF-1R sensitivity as critical variables. journals.physiology.org

4.5 Cell-culture Biotechnology

In CHO and HEK293 processes IGF-1 LR3 (10–100 ng mL⁻¹) raises viable cell density and mAb yield 30–60 % versus insulin (10 µg mL⁻¹), at >200-fold lower mass input, decreasing feed cost and downstream insulin carry-over. cellsciences.comRepligen

5. Emerging Clinical Interests

6. Safety and Tolerability

• Acute adverse effects: Transient hypoglycaemia possible with fasted injection at ≥40 µg kg⁻¹.

• Mitogenic risk: Persistent supraphysiologic exposure elevates IGF-1R-driven proliferation; long-term rodent studies show increased incidence of colonic aberrant crypt foci at ≥2-mg kg⁻¹.

• Antibody formation: Low immunogenicity in rabbits and primates; no neutralising antibodies detected after 90-day dosing.

Comparative safety matrix

7. Regulatory Landscape

IGF-1 LR3 is not approved by the FDA, EMA, or any major regulator. Commercial material is sold for research use onlyyet circulates in grey-market sports-medicine channels. Development hurdles include:

• Requirement for chronic-toxicity data addressing oncogenicity.

• Demonstrating a favourable risk–benefit ratio over recombinant human IGF-1 (mecasermin) which already holds orphan indications.

8. Future Directions

1. Formulation science – PEGylation or Fc-fusion to further extend half-life while modulating receptor bias.

2. Targeted delivery – muscle- or cartilage-specific conjugates to isolate anabolic effects and reduce systemic exposure.

3. Combination regimens – pairing with mTOR modulators or myostatin inhibitors to balance hypertrophy with metabolic safety.

4. Geroscience trials – evaluating low-dose cyclical IGF-1 LR3 for frailty endpoints and epigenetic age markers.

Selected References

1. Alexopoulos SJ et al. Nature Communications 11 (2020): 2397.

2. Voorhamme D et al. Cytotechnology 52 (2006): 141–152. 

3. Engel MG et al. J Alzheimer’s Dis 103 (2025): 113–126. 

4. Repligen Corp. LONG R³ IGF-I Cell Culture Supplement Data Sheet (2024). 

5. White A et al. Am J Physiol Endocrinol Metab (2025, in press).