Why Cell Culture Labs Use IGF-1 LR3 Instead of Insulin in Serum-Free Media

LynxLab · 24 October 2026 · 8 min read

How IGF-1 LR3 replaced insulin and serum in CHO and HEK293 culture, what Morris and Schmid found at Immunex in 2000, and why WADA lists IGF-1 analogues.

Photo: Karolina Grabowska (Kaboompics), Pexels

Most of the IGF-1 LR3 made in the world is never injected into anything. It goes into bioreactors. The modified growth factor was engineered in Adelaide as a cell culture supplement, and its main commercial life has been keeping Chinese hamster ovary cells alive and productive in media that contain no animal serum. The reasons it works there explain most of what is true about the molecule anywhere else.

The problem serum-free media had to solve

For decades, mammalian cells in culture were fed foetal bovine serum. Serum supplies growth factors, hormones, carrier proteins and attachment factors in one go, but it is variable from batch to batch, expensive, and a potential source of viruses and prions. Regulators and manufacturers pushed the biopharmaceutical industry towards defined, serum-free and ideally animal-component-free media.

Take the serum away and the cells lose their growth and survival signals. Something has to replace them, and for the IGF-1 receptor pathway the historical replacement was insulin, added at concentrations far above anything found in blood.

The limitation of insulin as a stand-in is the starting point for understanding why igf-1 lr3 found a market in biomanufacturing before it was known for anything else.

Why insulin is a poor stand-in for IGF-1

Insulin and IGF-1 are structurally related and each can bind the other's receptor, but only weakly. In culture, insulin's growth-promoting effect on many cell lines runs largely through the type-1 IGF receptor, which it activates poorly, so it has to be present in large amounts.

A 2006 paper in Molecular Biotechnology on human embryonic kidney (HEK293) cells states the comparison plainly: LONG R3 IGF-1 "is capable of supporting the growth and survival of Chinese hamster ovary cells in serum-free media at concentrations at least 200-fold lower than required for insulin". The authors describe the molecule as "specifically engineered for use in biopharmaceutical protein production in mammalian cells".

The same study found that LONG R3 IGF-1 activated both the type-1 IGF receptor and the insulin receptor more strongly at low concentrations than either insulin or native IGF-1 did. Researchers who buy igf-1 lr3 for receptor work should note one more detail from that paper: IGF receptor activation fell at higher concentrations, and the authors suggested the dose-response curve may be bell-shaped.

Why the LR3 form beats native IGF-1 in a dish

If the goal is to activate the IGF-1 receptor, why not use native IGF-1? Because cultured cells secrete IGF binding proteins into their medium, and those proteins capture native IGF-1 before it reaches the receptor. The arginine substitution at position 3 and the 13-amino-acid N-terminal extension that define the LR3 molecule were designed in the early 1990s to cut binding-protein affinity. The structural detail is in a companion post on what Long R3 means in IGF-1 LR3.

Sigma-Aldrich's product datasheet for the reagent says it "was developed as an inexpensive, high quality potent analog of IGF for use as a growth factor supplement for serum-free or low serum cell culture". It quotes an ED50 of 10 ng/ml for stimulating protein synthesis in L6 myoblasts, a molecular mass of about 9,110 daltons, and production in E. coli "in a completely animal-component free system".

That last phrase is the commercial point. A growth factor made in bacteria with no animal-derived inputs fits the animal-component-free media that regulators prefer. The long r3 igf-1 for research sold to laboratories is the same design, though research-grade material is not made or certified for manufacturing use.

Morris and Schmid at Immunex, 2000

The clearest published head-to-head comes from industry. Arvia Morris and J Schmid of Immunex Corporation in Seattle compared insulin and LongR3 in two serum-free CHO cell lines, each expressing a recombinant cytokine receptor, and published the results in Biotechnology Progress in 2000.

One line, VA12, could grow in serum-free medium with no added growth factor. The other, CL23, needed either insulin or LongR3 to grow at all. Under production conditions both lines needed a growth factor for best performance, and "LongR3 was better able to sustain the viability of both cell lines under production conditions than insulin".

Cell lines: two serum-free CHO lines, VA12 and CL23
Products: recombinant cytokine receptors
Finding: both insulin and LongR3 supported growth, but LongR3 kept cells viable longer in production
Conclusion: "LongR3 is the preferred growth factor for cell lines VA12 and CL23"

Viability in production is what a manufacturer cares about. A culture that stays alive for more days secretes more product per run, which is the metric that justified switching away from insulin. For a university lab comparing igf1 lr3 with insulin in a smaller flask, the same logic applies at a smaller scale.

From an Adelaide start-up to the biopharma supply chain

The molecule was designed at CSIRO and the Cooperative Research Centre for Tissue Growth and Repair in Adelaide and commercialised by GroPep, an Adelaide company. By the mid-2000s GroPep was in effect a one-product business. In August 2006 Chemical and Engineering News reported that Novozymes of Denmark had agreed to buy GroPep for almost 65 million US dollars, noting that GroPep's 12.7 million dollars of sales the previous year came "almost all from Long R3 IGF-1".

The magazine described the product as "a growth factor supplement used to produce vaccines, monoclonal antibodies, and other recombinant proteins in mammalian cell-based manufacturing systems that don't use animal serum as a cell nutrient source". That sentence is the molecule's job description.

The reagent remains a catalogue item at the major life-science suppliers today, which is why it is easy for a UK lab to find igf-1 lr3 uk stock from research suppliers as well as from the manufacturing-grade channel.

Why the same molecule is on the WADA list

A cell culture additive and a doping agent sound like different things, but they are one peptide. The World Anti-Doping Agency's 2026 Prohibited List, in force from 1 January 2026, prohibits "insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues" at all times under section S2.3, growth factors and growth factor modulators. IGF-1 LR3 is an analogue of IGF-1 and falls squarely inside that wording.

UK Anti-Doping applies the same list to athletes in the UK and published its summary of the 2026 changes after WADA released the list on 24 September 2025. The US Anti-Doping Agency's guidance page on IGF-1 states that "all forms of exogenous IGF-1 are prohibited at all times, and any substance containing any form of exogenous IGF-1 should be considered prohibited".

The only licensed IGF-1 medicine is mecasermin, a recombinant native IGF-1 sold as Increlex. IGF-1 LR3 has no marketing authorisation anywhere. A 2023 review of doping and sports endocrinology published by Elsevier España notes that IGF-1 has been prohibited by WADA since 2003 and describes modified analogues with a prolonged half-life among the forms seen in doping. In the UK IGF-1 LR3 is sold for laboratory research only.

What a research buyer should check

For culture work the relevant specifications are the ones a manufacturer would check: identity by mass spectrometry, purity by HPLC, and the absence of carrier proteins that would defeat the point of a defined medium. Endotoxin matters for cell work too, since bacterial lipopolysaccharide carried over from E. coli expression can confound a growth assay.

LynxLab stocks igf-1 lr3 1mg for research use in 1mg vials at £49.99, tested to 99% purity with the lab report on the product page. The batch certificate of analysis shows the HPLC and mass spectrometry results so the parent mass can be compared with the 9,110 dalton figure on the Sigma-Aldrich datasheet.

The published concentration data give a reference point. Sigma-Aldrich quotes an ED50 of 10 ng/ml in L6 myoblasts, and the HEK293 study reported activity at concentrations at least 200-fold below insulin's working range. At 10 ng/ml, 1mg is enough for around 100 litres of medium, which is one reason the reagent is sold in milligram rather than gram amounts.

Frequently asked questions

Can IGF-1 LR3 replace insulin in CHO cell culture?

Published work says yes for the lines tested. Morris and Schmid at Immunex found in 2000 that LongR3 sustained viability of two serum-free CHO lines better than insulin under production conditions, and a 2006 study reported it supported CHO growth at concentrations at least 200-fold lower than insulin. Response varies by cell line and clone.

What concentration of IGF-1 LR3 is active in cell culture?

Sigma-Aldrich's datasheet quotes an ED50 of 10 ng/ml for protein synthesis in rat L6 myoblasts. The HEK293 study found receptor activation at low nanogram-per-millilitre concentrations and a fall-off at higher levels, suggesting a bell-shaped curve. Any new cell line needs its own titration.

Is IGF-1 LR3 banned by WADA?

Yes. The 2026 Prohibited List bans IGF-1, mecasermin, "and its analogues" at all times under section S2.3, and IGF-1 LR3 is an IGF-1 analogue. UK Anti-Doping enforces the same list in the UK.

Is IGF-1 LR3 used to make medicines?

Yes, as a manufacturing additive rather than an ingredient. Chemical and Engineering News described it in 2006 as a growth factor supplement for producing vaccines, monoclonal antibodies and other recombinant proteins in serum-free mammalian cell culture. It is a raw material in the culture step, not an ingredient of the finished medicine.

Sources

Research use only

IGF-1 LR3 from LynxLab

1mg vials from £49.99. ≥99% purity, lab report on the page. Same-day dispatch, UK stock.

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