Innovacrin IGF-1 LR3 Innovacrin™ products are furnished strictly for in-vitro applications

IGF-1 LR3 Information


IGF-1 LR3, also known as Long-Arginine-3-IGF-1, is an analogue of human IGF-1 that has been modified to include a 13 amino acid N-terminus extension and the substitution of Arginine for Glutamic Acid at position 3. As a result of these modifications, IGF-1 LR3 is approximately three times more potent than IGF-1 and possesses an increased half-life due to lowered affinity for binding to the Insulin-Like Growth Factor-Binding Proteins (IGFBPs). IGF-1 LR3 retains the ability to bind agonistically to the IGF-1 receptor with improved metabolic stability, relative to IGF-1. The supplementation of mammalian cell cultures with Long R3 IGF-1 at a much lower concentration results in more highly elevated productivity than with standard concentrations of insulin and/or standard IGF-1. IGF-1 LR3 is more able to stimulate the type 1 IGF receptor and thus induce a higher level of activation of intracellular signaling, which is responsible for promoting cell proliferation and the inhibition of apoptosis.

The amino acid sequence (three letter) of IGF-1 LR3 is is Met-Phe-Pro-Ala-Met-Pro-Leu-Ser-Ser-Leu-Phe-Val-Asn-Gly-Pro-Arg-Thr-Leu-Cys-Gly-Ala-Glu-Leu-Val-Asp-Ala-Leu-Gln-Phe-Val-Cys-Gly-Asp-Arg-Gly-Phe-Tyr-Phe-Asn-Lys-Pro-Thr-Gly-Tyr-Gly-Ser-Ser-Ser-Arg-Arg-Ala-Pro-Gln-Thr-Gly-Ile-Val-Asp-Glu-Cys-Cys-Phe-Arg-Ser-Cys-Asp-Leu-Arg-Arg-Leu-Glu-Met-Tyr-Cys-Ala-Pro-Leu-Lys-Pro-Ala-Lys-Ser-Ala

What does the IGF-1 "Long R3" abbreviation stand for?

IGF-1 LR3 (Long R3 Insulin-Like Growth Factor-1) is a synthetic analogue of IGF-1 that has two modifications:

  • IGF-1 LR3 possesses the substitution of a Glutamic Acid for an Arginine (ARG or R) at the third position in its amino acid sequence. This substitution is commonly abbreviated as "Arginine-3", "Arg3" or "R3".
  • IGF-1 LR3 consists of 83 amino acids, relative to the 70 amino acid sequence of human IGF-1, due to a 13 amino acid extension (MFPAMPLLSLFVN) at its N-terminus. This 13 amino acid extension is commonly abbreviated as "Long" or simply "L" in the IGF-1 LR3 / Long-Arginine-3-IGF-1 name.

Long (N-terminus extension)  R3 (Arginine substitution at position 3)  IGF-1 (Insulin-Like Growth Factor-1)

The result of these modifications is that IGF-1 LR3 does not bind as strongly to the IGFBPs, which modify the biological actions of IGF-1. Resultantly, IGF-1 LR3 binds to the type 1 IGF-1 receptor with similar affinity to that of wild type IGF-1, but with higher biological activity and has several advantages over recombinant insulin.

IGFB Binding and The Increased Biological Activity of LR3 IGF-1

By resisting IGFBP-binding, IGF-1 LR3 has a greater physiologic effect than IGF-1 does. The longer duration of action allows for smaller amounts to be used with the same effects. Some IGF-1 derivatives, such as the GPE derivative, made up of just the last three N-terminal amino acids of the IGF-1 protein, have been shown to have therapeutic effects in neurological injuries like stroke. Most studies concerning the effects of IGF-1 derivatives have been carried out in animal models, with little to no data available for humans.

Insulin Like Growth Factor Receptor Interactions

IGF-1 binds to at least two cell surface receptors: IGF-1R and the insulin receptor. The IGF-1 receptor is referred to as the "physiologic" receptor because IGF-1 binds to it with significantly higher affinity (approximately 100 times higher) than it does to the insulin receptor. By binding to IGF-1R, IGF-1 can affect metabolism, cell growth (hypertrophy), differentiation and cell division (hyperplasia), prevention of cell death (apoptosis), normal development, and even malignant growth. IGF-1R has been implicated in several different types of cancer include breast, prostate, and lung cancer. IGF-1 also binds to the insulin receptor and activates it, thereby encouraging cells to take up glucose from the blood stream. The effects of IGF-1 on muscle cells are three-fold. Firstly, IGF-1 encourages hyperplasia, or an increase in the number of muscle cells. Secondly, IGF-1 has a strong effect on skeletal muscle - In regards to the life span of satellite cells. Satellite cells support muscle cells, providing them with needed nutrients and helping them to operate efficiently. By increasing the lifespan of these cells, IGF-1 helps to increase their number with muscle tissue. Finally, IGF-1 encourages differentiation of myoblasts, which is to say that it encourages the conversion of stem cell progeny from nonspecific pluripotent stem cells into dedicated muscle tissue. In this way, IGF-1 increases the rate of muscle development by increasing the rate at which generic stem cells are converted to muscle cells.