INSULIN-LIKE GROWTH FACTOR (IGF1-LR3)

Mechanism of Action
IGF-1 LR3 is a recombinant analog of insulin-like growth factor 1 (IGF-1), modified to increase its potency and duration of action. It contains an arginine substitution at position 3 of the IGF-1 sequence and an additional 13 amino acids at the N-terminal end. These modifications markedly reduce its affinity for IGF-binding proteins (IGFBPs), thereby increasing the fraction of free, biologically active IGF-1 and prolonging its half-life. As a result, IGF-1 LR3 exhibits approximately threefold greater anabolic potency than native IGF-1.
IGF-1 LR3 binds to the IGF-1 receptor on the cell surface, activating tyrosine kinase signaling cascades (PI3K/Akt and Raf/MEK/ERK pathways) that stimulate protein synthesis, cell proliferation, and survival while inhibiting apoptosis. In essence, it mimics the action of endogenous IGF-1—the primary mediator of growth hormone—promoting sustained muscle and bone growth.
 
Clinical or Therapeutic Uses
There are no widely approved clinical uses for IGF-1 LR3 in general medical practice. However, standard recombinant IGF-1 (mecasermin) is used clinically in children with severe primary IGF-1 deficiency (e.g., Laron syndrome) to promote linear growth.
IGF-1 LR3 is being investigated at the preclinical level for potential applications in regenerative medicine and degenerative diseases. Due to its high bioactivity and ability to stimulate cellular proliferation, it has been proposed for tissue repair and muscle regeneration. It has also been explored for possible roles in metabolic disorders (e.g., type 2 diabetes), as in vitro studies suggest that IGF-1 LR3 can regulate glucose uptake in adipocytes. However, no regulatory authority has formally approved these indications to date.
Outside the medical setting, IGF-1 LR3 is used illicitly as an anabolic agent in sports to increase muscle mass and enhance performance. Following the commercial availability of IGF-1 analogs, reports of abuse increased similarly to what was observed with growth hormone. The World Anti-Doping Agency (WADA) prohibits IGF-1 and its derivatives due to their performance-enhancing effects, although detection in anti-doping tests presents technical challenges.
 
Side Effects and Associated Risks
IGF-1 LR3 shares many risks with endogenous IGF-1 and growth hormone administration. One of the most common adverse effects is hypoglycemia, due to its insulin-mimetic action that increases peripheral glucose uptake. Users may experience symptoms of low blood glucose such as sweating, dizziness, and fatigue, and severe hypoglycemia can lead to seizures.
Other reported effects include fluid retention with edema, joint pain (arthralgia), muscle pain (myalgia), headaches, and jaw pain in individuals receiving exogenous IGF-1. These effects partly mirror manifestations of acromegaly (chronic excess of GH/IGF-1), including soft-tissue overgrowth. Prolonged IGF-1 exposure has been associated with hypertrophy of organs such as the liver and kidneys.
A major concern is its unwanted proliferative potential. The IGF-1/IGF-1 receptor pathway plays a role in the survival and proliferation of malignant cells. Consequently, there is concern that IGF-1 LR3 could promote the development or progression of occult neoplasms if used without medical supervision. Studies in oncologic models indicate that at high doses, IGF-1 LR3 can stimulate tumor growth alongside its muscle-building effects.