IGF-1 LR3 is a modified version of IGF-1, the growth-factor signal involved in cell growth, repair, and metabolism. Unlike approved IGF-1 medicine (mecasermin/Increlex), LR3 is mainly a research compound and should not be treated as a safe or approved therapy. It has no FDA-approved human use and is prohibited in sport.
IGF-1 LR3 is an 83-amino-acid IGF-1 analog engineered to reduce IGF-binding-protein interaction and increase free IGF-like activity in non-clinical systems. Because no validated human dosing or safety dataset exists, the clinical discussion here focuses on risk, regulatory status, and comparison to mecasermin - not protocol recommendations. It is best characterized as a cell-culture / signaling reagent.
Long-R3 IGF-1 combines a 13-amino-acid N-terminal extension with a Glu3→Arg3 substitution. It is commonly catalogued at ~9,117.6 Da (C400H625N111O115S9, 83 residues), and the modifications reduce IGFBP affinity by roughly 100- to 1000-fold, increasing IGF-1R-directed signaling in cell systems. Mechanistic interest centers on IGF-1R → PI3K/Akt/mTOR and MAPK/ERK, with species-specific animal data and no validated human translation.
IGF-1 LR3 is positioned in this atlas as a research analog of IGF-1, not a therapeutic protocol peptide. Its real, well-documented use is as a cell-culture growth-factor reagent; its human evidence base is essentially absent. The page deliberately keeps it separate from FDA-approved mecasermin and frames its dosing section as a research-concentration model with the human-injection calculator locked.
IGF-1 LR3 is designed to act like IGF-1 and switch on growth and survival signaling in cells - but it was modified so the body's binding proteins hold onto it less tightly, leaving more of it free to act.
LR3 is modeled as an IGF-1R agonist that drives proliferation, survival, and protein-synthesis pathways. Its defining feature is reduced IGFBP affinity, which raises free-ligand availability in culture and animal models. The downstream biology (PI3K/Akt/mTOR, MAPK/ERK) is well established for the IGF axis generally; LR3-specific human translation is not.
Mechanistically, LR3 engages IGF-1R (a receptor tyrosine kinase) to activate IRS/PI3K/Akt/mTOR and Ras/Raf/MEK/ERK. The Arg3 + 13-aa extension reduces IGFBP sequestration, increasing receptor-directed signaling. Native IGF-1 signaling data are far stronger than LR3-specific data, and the systemic animal effects are species-dependent.
IGF-1 LR3 has no approved therapeutic human dose, no FDA-approved indication, and no validated patient protocol. This section is built as a research-concentration model with a human-use safety lock: a cell-culture concentration engine (ng/mL · µg/L) plus an explicitly disabled human-injection calculator. The FDA-approved comparator, mecasermin/Increlex, is a different molecule - native recombinant human IGF-1 - and its dosing must not be transferred to LR3.
10-100 µg/L (10-100 ng/mL), with a recommended starting point around 50 µg/L.| Band | Working concentration | Interpretation | Basis |
|---|---|---|---|
| Low | 10 µg/L = 10 ng/mL | Conservative starting exploration in responsive cells | Product FAQ range |
| Standard | 50 µg/L = 50 ng/mL | Suggested starting point for optimization | Product FAQ |
| High | 100 µg/L = 100 ng/mL | Upper end of common research range; CHO poster methods | Product FAQ / CHO poster |
Do not create µg/kg human bands for IGF-1 LR3. Any µg/kg table would imply a human-use protocol that is not supported.
| Body weight | IGF-1 LR3 dose |
|---|---|
| 55 kg | Not established |
| 65 kg | Not established |
| 75 kg | Not established |
| 85 kg | Not established |
| 95 kg | Not established |
| 105 kg | Not established |
No validated human µg/kg model exists for IGF-1 LR3. This table is intentionally shown as "unavailable" rather than interpolated.
| Trigger | Action | Rationale |
|---|---|---|
| Cell viability ≥90%, mid-log growth, stable expression | Test 10-50 µg/L | Optimize by cell line and process |
| No growth/productivity response at 10-50 µg/L | Compare 50-100 µg/L + no-LR3 control | Response is cell-line dependent |
| Reduced viability or abnormal morphology | Hold/reduce; check osmolality, pH, contamination, media compatibility | Cell stress may be unrelated to LR3 but should stop escalation |
| Filter loss or inconsistent assay recovery | Validate filtration membrane & handling | Peptide adsorption / filtration loss affects recovery |
| Any clinical or human-administration context | HARD STOP | No approved LR3 human protocol |
| Marker | Why it matters | Validated for LR3? |
|---|---|---|
| Fasting glucose | IGF-axis drugs can lower glucose; mecasermin warns of severe hypoglycemia | No - risk-context only |
| IGF-1 serum level | Reflects IGF axis but may not detect LR3 reliably | No - not validated |
| IGFBP-3 | Binding-protein axis may change with IGF exposure | No - research marker |
| Insulin / A1c | Insulin-like metabolic effects; long-term glucose | No - not LR3-specific |
| CMP / liver / renal | General safety context | No - not LR3-specific |
| Fundoscopic exam | Mecasermin warns of intracranial hypertension | No - comparator-derived |
| Cancer screening / history | Mecasermin contraindicates malignancy/history of malignancy | No - hard-risk screen |
Research/education only - for cell-culture media supplementation, not human dosing. The human-injection calculator (Mode B, below) is locked. Formula: peptide needed (µg) = target (µg/mL) x volume (mL); draw (mL) = peptide / stock (µg/mL).
No validated human IGF-1 LR3 dose exists. The human administration calculator is disabled. IGF-1 LR3 is not FDA-approved and has no validated human dosing, route, or safety dataset; the approved IGF-1 drug is mecasermin/Increlex, a different molecule. This page intentionally provides only a cell-culture concentration tool.
Reconstitute to ≥1 mg/mL (e.g. 100 mM acetic acid) per product guidance; confirm full dissolution and avoid vortexing-induced denaturation.
Verify against supplier COA and mass spec before any database lock; the CAS/identifier conflict and gray-market quality concerns make documentation essential.
Validate membrane compatibility; peptide adsorption can reduce effective concentration and confound dose-response.
Always include a no-LR3 control and, where relevant, an insulin comparator; response is cell-line dependent.
Store lyophilized and reconstituted aliquots per product guidance; minimize freeze-thaw of a labile ~9 kDa protein with three disulfide bonds.
No human administration. If a workflow drifts toward human use, stop - there is no validated protocol and this is a regulated, WADA-prohibited substance.
IGF-1 LR3's documented combinations are cell-culture and animal-research pairings, not human stacks. The performance-world pairings (with GH or anabolics) are extrapolations with no human safety dossier, and the engine treats IGF-axis stacking in anyone with malignancy risk as a hard constraint.
Do not stack IGF-axis agents in any person with active or prior malignancy risk without specialist medical oversight. Mecasermin's label includes malignancy-related contraindications and warnings, and IGF-1 LR3 lacks any human safety dossier - so the proliferative biology applies by analogy with none of the bounding data. Treat malignancy or cancer predisposition, hypoglycemia-prone states, pregnancy/lactation, and competitive-sport status as exclusion conditions. And keep IGF-1 LR3 strictly separate from native rhIGF-1 / mecasermin - they do not share dosing, PK, or safety claims.
Almost all human-relevant safety information for IGF-1 LR3 is inferred - from mecasermin's label, from IGF-axis biology, and from animal studies. Mecasermin's warnings (severe hypoglycemia, hypersensitivity, intracranial hypertension, lymphoid hypertrophy, SCFE, scoliosis progression, malignant-neoplasia reports) frame the IGF axis as high-risk. LR3 adds a specific worry: by engineering away IGFBP binding, it removes a natural brake on IGF-1 signaling, with no long-term carcinogenicity data to bound the consequence.
| Condition | Concern | Severity |
|---|---|---|
| Active malignancy or history of malignancy | IGF-axis proliferative signaling; mecasermin malignancy warning | High |
| Hypoglycemia-prone state | IGF-like glucose lowering | High |
| Diabetes on insulin / secretagogues | Additive glucose effects | High |
| Pregnancy / lactation | No LR3 safety data | High |
| Pediatric non-indicated growth use | Growth-plate / overgrowth risks; mecasermin is tightly indicated | High |
| Closed epiphyses (growth promotion) | Mecasermin contraindication context | High |
| Intracranial-hypertension history | Mecasermin warning context | Moderate-High |
| Scoliosis / rapid-growth risk | Mecasermin warning context | Moderate |
| Active athlete under WADA code | IGF-1 and analogs prohibited | High |
| Unverified gray-market product | Purity, sterility, dose, identity risk | High |
If IGF-axis exposure occurs in any context, hypoglycemia is the most immediate analog risk; glucose is a risk-context marker only, not a validated LR3 endpoint.
Cancer history/predisposition is a hard exclusion by analogy to mecasermin; the IGFBP-bypass design makes this the dominant chronic concern.
Reflect the axis but are not validated to track LR3 exposure; interpret cautiously and only as research context.
COA + mass spec for identity, purity, and concentration; the CAS conflict and gray-market sourcing make this essential.
SCFE, scoliosis, and intracranial-hypertension cautions carry over from mecasermin's label as comparator-derived warnings.
Any human-administration workflow is a hard stop - there is no validated protocol, and the substance is WADA-prohibited.
IGF-1 LR3 has moderate non-clinical mechanistic plausibility and solid practical evidence as a cell-culture growth-factor reagent, but very weak human clinical evidence - effectively none. Its honest position on the Atlas is a research analog of IGF-1, not a therapeutic protocol peptide. What is missing: human PK, dose-ranging, route-specific safety, long-term carcinogenicity surveillance, validated biomarkers, and clinical outcomes.
Francis and colleagues described novel recombinant fusion-protein IGF-I analogs - the design lineage behind Long-R3 IGF-I, establishing the engineering rationale of an N-terminal extension plus Arg3 substitution to reduce IGFBP binding.
Product science describes LONG R3 IGF-I increasing cell density, viability, and culture duration in serum-free / low-serum systems, with a 10-100 µg/L working range and a recommended ~50 µg/L starting point - the molecule's strongest, most defensible use case.
Long-R3 IGF-I infusion stimulated organ growth but reduced plasma IGF-I, IGF-II, and IGF-binding-protein concentrations in guinea pigs - a clear in-vivo demonstration of both growth signaling and endocrine-feedback suppression.
In pigs, Long-[R3] IGF-I reduced growth and endocrine markers, and reduced-IGFBP-affinity IGF-I variants were more potent in rats but depressed growth in pigs - together a strong warning against cross-species (and human) extrapolation.
Intranasal LR3-IGF-1 induced amyloid-beta uptake in BV-2 microglia but did not reduce Abeta40/Abeta42 burden in the 5XFAD brain - a mechanistic signal without a disease-modifying outcome, and no basis for human inference.
A native rhIGF-I study found slow SC absorption with Tmax ~7 h after single 40-80 µg/kg injections in healthy volunteers. Included strictly as a comparator - the mecasermin clinical record likewise defines approved IGF-1 use, not LR3 dosing.
Overall, IGF-1 LR3 has moderate non-clinical mechanistic plausibility and solid cell-culture reagent evidence (growth, survival, and productivity in serum-free mammalian culture), but very weak human evidence - no validated dosing, efficacy, or safety dataset. Native IGF-1 biology and monitoring are far better characterized and should not be conflated with LR3. It belongs on the Atlas as a research analog of IGF-1, framed by risk, regulatory status, and comparison to mecasermin - not as a therapeutic protocol.
| Evidence type | LR3-specific? | Summary | Grade |
|---|---|---|---|
| Human therapeutic trials | No | No validated human dosing/efficacy/safety dataset | D |
| Native rhIGF-I PK | Comparator | Slow SC absorption, Tmax ~7 h (not LR3) | B |
| Mecasermin label / review | Comparator | Defines approved IGF-1 use & risk framework | D |
| Guinea-pig infusion | Yes | Organ growth + reduced circulating IGFs/IGFBPs | C |
| Pig growth model | Yes | Reduced growth and endocrine markers (species-specific) | C |
| IGF analog comparison | Class | Reduced-IGFBP variants: potent in rats, depress growth in pigs | C |
| Cell culture / CHO | Yes | Growth, survival, productivity in serum-free culture | P |
| Intranasal mouse AD | Yes | Microglial Abeta uptake; no Abeta burden reduction | C/P |
The crucial comparison is that IGF-1 LR3 is not mecasermin. Native rhIGF-1 is an FDA-approved drug with a defined pediatric indication; LR3 is an engineered, IGFBP-evading research analog with no approval. IGF-1 DES and PEG-MGF are further research-class relatives, and GH/somatropin sits upstream as the endocrine driver of endogenous IGF-1.
| Feature | IGF-1 LR3 | Mecasermin / rhIGF-1 | IGF-1 DES | PEG-MGF |
|---|---|---|---|---|
| Primary use | Research / cell-culture / non-clinical IGF-axis model | Severe primary IGFD growth failure in children | Shorter IGF-1 analog (research) | MGF-analog research peptide |
| Mechanism class | IGF-1 analog; reduced IGFBP affinity; IGF-1R agonist | Native recombinant human IGF-1 | N-terminal-truncated; local IGF signaling | IGF-1 splice-variant-related repair model |
| Evidence tier | P/C (preclinical/culture) | A/B/D (FDA label evidence) | P/C | P/C |
| Route context | Cell culture, animal studies | SC injection by prescription | Research only | Research only |
| Regulatory status | Not FDA-approved; WADA-prohibited class | FDA-approved drug | Not FDA-approved | FDA has flagged peptide-compounding risks |
| IGFBP behavior | ~1000-fold reduced binding (evades buffer) | Normal IGFBP-3/ALS binding | Reduced IGFBP binding (local action) | Distinct MGF-related mechanism |
| Key caution | No human data; oncogenic-bypass concern | Hypoglycemia, neoplasia, SCFE (pediatric) | Different binding/potency profile | Research-only; unvalidated |