IGF-DES (2mg)

IGF-1 DES (Des(1-3) IGF-1, Insulin-Like Growth Factor-1 DES, 2mg): A Recombinant 67-Amino-Acid Truncated Analogue of Human Insulin-Like Growth Factor 1 (IGF-1, Somatomedin C) with the First Three N-Terminal Amino Acids (Glycine-Proline-Glutamic Acid, Gly-Pro-Glu) Deleted — Designed for Enhanced Receptor-Binding Potency, Reduced IGF-Binding Protein (IGFBP) Affinity, and Rapid Onset of Action — the 2mg Vial Format (Larger Research Quantity) for Investigational Research in Localized Muscle Hypertrophy, Site-Specific Tissue Growth, Post-Workout Recovery, and Body Composition

IGF-1 DES (also known as Des(1-3) IGF-1, IGF-1 DES, des-IGF-1, or [Des(1-3)]IGF-1) is a recombinant 67-amino-acid truncated analogue of human insulin-like growth factor 1 (IGF-1, also known as somatomedin C), with a molecular weight of approximately 7.35 kDa (7,350 Daltons). IGF-1 DES is created by deleting the first three N-terminal amino acids of native IGF-1 — specifically, the tripeptide Glycine-Proline-Glutamic Acid (Gly-Pro-Glu, GPE) at positions 1, 2, and 3 of the native 70-amino-acid IGF-1 molecule. This N-terminal truncation removes three residues from the B domain N-terminus, resulting in a 67-amino-acid peptide (positions 4-70 of native IGF-1) that retains the core IGF-1 structure and receptor-binding domain but has significantly altered pharmacokinetic and pharmacodynamic properties compared to native IGF-1. The deletion of the first three amino acids, particularly the removal of glutamic acid at position 3 (Glu3), is the key structural modification that defines IGF-1 DES and gives it its characteristic properties. Glu3 is a critical residue in the native IGF-1 molecule that forms important electrostatic interactions (salt bridges and hydrogen bonds) with positively charged residues (arginine, lysine) in the N-terminal binding domains of IGF-binding proteins (IGFBPs). By deleting Glu3 (along with Gly1 and Pro2), IGF-1 DES loses this critical IGFBP-binding determinant, resulting in dramatically reduced affinity for IGFBPs — particularly IGFBP-1, IGFBP-2, and IGFBP-3 — with studies showing that IGF-1 DES has approximately 100-1000 fold lower affinity for IGFBPs compared to native IGF-1 (similar in magnitude to the reduction seen with the Arg3 substitution in IGF-1 LR3, but achieved through deletion rather than substitution). This reduced IGFBP affinity means that a much larger fraction of administered IGF-1 DES remains in the biologically active "free" (unbound) form, which can readily access tissues and activate IGF-1 receptors, rather than being sequestered by IGFBPs (as ~75-80% of native IGF-1 is, in the ternary complex with IGFBP-3 and the acid-labile subunit [ALS]). In addition to reduced IGFBP affinity, the N-terminal truncation in IGF-1 DES also affects the peptide's interaction with the IGF-1 receptor itself. Interestingly, despite (or perhaps because of) the N-terminal truncation, IGF-1 DES has been reported to have enhanced receptor-binding affinity and potency compared to native IGF-1 in some in vitro assays — with some studies reporting that IGF-1 DES is approximately 2-10 times more potent than native IGF-1 in stimulating IGF-1 receptor autophosphorylation, downstream signaling (PI3K/Akt and MAPK/ERK), and cellular responses (proliferation, protein synthesis, glucose uptake). The mechanism for this enhanced potency is thought to be related to the removal of the N-terminal tripeptide (Gly-Pro-Glu), which may act as a partial "inhibitory domain" or steric hindrance in native IGF-1 that slightly reduces receptor-binding efficiency; removing it may allow the remaining 67-amino-acid peptide to bind the IGF-1 receptor with higher affinity or in a more optimal conformation. However, it is important to note that the enhanced in vitro potency of IGF-1 DES does not necessarily translate to enhanced in vivo potency per administered dose, because IGF-1 DES has a significantly shorter half-life than IGF-1 LR3 (due to its smaller molecular size [7.35 kDa vs 9.11 kDa] resulting in more rapid renal clearance, and because it does not have the N-terminal extension that protects LR3 from proteolytic degradation). IGF-1 DES exerts its biological effects by binding to and activating the IGF-1 receptor (IGF-1R, also known as CD221) — a heterotetrameric receptor tyrosine kinase (RTK) of the insulin receptor family, consisting of two extracellular α-subunits (ligand-binding domain) and two transmembrane β-subunits (intracellular tyrosine kinase domain), linked by disulfide bonds. When IGF-1 DES binds to the extracellular α-subunits, it induces a conformational change that activates the β-subunit tyrosine kinases through trans-autophosphorylation (at Tyr1131, Tyr1135, Tyr1136 in the activation loop, and Tyr950 in the juxtamembrane region), creating docking sites for downstream signaling molecules. The two major downstream signaling pathways are: (1) PI3K/Akt pathway (the primary pathway for metabolic and cell survival effects) — insulin receptor substrate (IRS-1/2) proteins are recruited and phosphorylated, activating PI3K, which generates PIP3 at the cell membrane, leading to Akt activation (via PDK1 at Thr308 and mTORC2 at Ser473); activated Akt then phosphorylates downstream targets including mTORC1 (increasing protein synthesis via p70S6K activation and 4E-BP1 inhibition — the primary mechanism for muscle hypertrophy), GSK-3β (increasing glycogen synthesis), FOXO transcription factors (inhibiting apoptosis and muscle atrophy genes like MuRF1 and Atrogin-1), Bad and caspase-9 (inhibiting mitochondrial apoptosis), eNOS (increasing nitric oxide production for vasodilation and angiogenesis), and AS160 (increasing GLUT4 translocation and glucose uptake); and (2) MAPK/ERK pathway (the primary pathway for mitogenic/proliferative effects) — Grb2-SOS recruitment activates Ras, which activates the Raf-MEK-ERK1/2 kinase cascade, leading to ERK nuclear translocation and phosphorylation of transcription factors (Elk-1, c-Myc, c-Fos, c-Jun, AP-1) that regulate genes involved in cell proliferation, differentiation, and survival. The net biological effects of IGF-1 DES (mediated through IGF-1R activation and these downstream pathways) are similar to those of native IGF-1 and IGF-1 LR3, but with important differences in kinetics and tissue distribution due to its unique pharmacokinetic profile: (1) Potent anabolic / muscle hypertrophic effects — IGF-1 DES stimulates muscle protein synthesis (via PI3K/Akt/mTORC1), inhibits muscle protein breakdown (via FOXO inhibition), and promotes satellite cell activation and proliferation — these effects are the primary reason for IGF-1 DES's popularity in bodybuilding and performance enhancement research, particularly for site-specific or localized muscle growth (because of its short half-life and rapid onset, IGF-1 DES is often injected directly into or near specific muscles to promote localized hypertrophy, with less systemic exposure than longer-acting analogues like LR3); (2) Fat loss / lipolytic effects — IGF-1 DES promotes fat breakdown (lipolysis) and inhibits lipogenesis, leading to reduced fat mass; (3) Rapid onset and short duration of action — due to its small molecular size (7.35 kDa) and reduced IGFBP binding, IGF-1 DES has a relatively short half-life (estimated at approximately 20-60 minutes in rodents and larger animals, although exact human data is limited), which means it has a rapid onset of action (effects begin within minutes of administration) but a relatively short duration (effects may peak within 1-2 hours and largely resolve within 4-8 hours); this pharmacokinetic profile makes IGF-1 DES particularly suitable for timed administration around workouts (e.g., pre-workout or post-workout injection to maximize the anabolic window of muscle protein synthesis and recovery) and for localized/site-specific injection (because the short half-life limits systemic distribution, keeping more of the peptide's effects localized to the injection site); (4) Tissue repair and recovery — IGF-1 DES promotes tissue repair, wound healing, muscle repair after exercise-induced damage, and connective tissue repair; (5) Metabolic effects — IGF-1 DES has insulin-like metabolic effects (increased glucose uptake, glycogen synthesis, reduced hepatic gluconeogenesis), although the short half-life may limit the duration of these metabolic effects; (6) Reduced systemic side effects compared to longer-acting analogues — because of its short half-life and rapid clearance, IGF-1 DES may have less sustained systemic exposure and potentially fewer systemic side effects (such as prolonged hypoglycemia, fluid retention, or carpal tunnel syndrome) compared to longer-acting analogues like IGF-1 LR3, particularly when used at lower doses or for localized injection; however, this benefit must be balanced against the need for more frequent dosing (due to the short half-life). The 2mg vial format contains 2000mcg of IGF-1 DES, which is a larger quantity suitable for more extensive research programs, longer-duration studies, or protocols requiring higher or more frequent dosing (due to IGF-1 DES's short half-life, more frequent dosing is often needed compared to longer-acting analogues like LR3). Typical in vivo research doses of IGF-1 DES range from 20-100 mcg per administration (SC or IM), often administered 1-2 times daily (due to the short half-life, more frequent dosing than LR3 is often used), with timing around workouts (pre- or post-workout) being common in bodybuilding research protocols; at these doses, a 2mg vial provides 20-100 doses (sufficient for 10-100 days of once-daily dosing, or 5-50 days of twice-daily dosing). For higher-dose or more frequent protocols, the 2mg vial provides adequate quantity. For in vitro cell culture, IGF-1 DES is typically used at concentrations ranging from 1 ng/mL to 1 μg/mL (with 10-100 ng/mL being commonly used for cell proliferation/survival assays), and a 2mg vial (7.35 kDa) provides approximately 272 nanomoles of peptide, sufficient for numerous cell culture experiments. Reconstitution: add 2-20 mL of bacteriostatic water (or sterile water for in vitro use) to yield 1-0.1 mg/mL (1000-100 mcg/mL); for example, adding 5 mL yields 0.4 mg/mL (400 mcg/mL), so a 20 mcg dose = 0.05 mL, 50 mcg = 0.125 mL, 100 mcg = 0.25 mL, 200 mcg = 0.5 mL, 400 mcg = 1.0 mL, 2mg = 5.0 mL; adding 10 mL yields 0.2 mg/mL (200 mcg/mL), so a 20 mcg dose = 0.1 mL, 50 mcg = 0.25 mL, 100 mcg = 0.5 mL, 200 mcg = 1.0 mL, 400 mcg = 2.0 mL, 2mg = 10.0 mL. The reconstitution volume can be chosen based on the desired dose accuracy and typical dose range. Reconstituted IGF-1 DES is stable for 14-30 days when refrigerated at 4°C and protected from light; the lyophilized powder is stable for 24 months from manufacture when stored at -20°C, protected from light and moisture. The safety profile of IGF-1 DES requires careful consideration, as it is a potent metabolic and mitogenic peptide with potential side effects, particularly at supraphysiological doses. Common side effects include: (1) Hypoglycemia — IGF-1 DES has insulin-like glucose-lowering effects, and hypoglycemia can occur, particularly at higher doses or in individuals with low body fat or who are fasting; however, because of IGF-1 DES's short half-life, the duration of hypoglycemic effects may be shorter than with longer-acting analogues like LR3; symptoms include shakiness, sweating, dizziness, confusion, irritability, hunger, blurred vision, and in severe cases, loss of consciousness or seizures; blood glucose monitoring is recommended, particularly when starting therapy or adjusting doses; (2) Local injection site reactions — because IGF-1 DES is often used for localized/site-specific injection, local reactions at the injection site may occur, including redness, swelling, pain, itching, or mild inflammation; these are usually mild and transient, but rotating injection sites is recommended; (3) Headache — particularly at the initiation of therapy or at higher doses, possibly due to vasodilatory effects or changes in intracranial pressure; usually mild and transient; (4) Nausea / gastrointestinal effects — mild nausea or stomach discomfort may occur, particularly at the initiation of therapy; usually mild and transient; (5) Fatigue / lethargy — some individuals report fatigue or tiredness, particularly if hypoglycemia occurs; (6) Joint pain / arthralgia — may occur at higher doses or with prolonged use, possibly due to tissue growth or fluid retention; (7) Edema / fluid retention — may occur at higher doses, although potentially less than with longer-acting analogues due to the shorter half-life; (8) Carpal tunnel syndrome / paresthesia — may occur at higher doses or with prolonged use, due to fluid/tissue swelling compressing the median nerve; (9) Skin changes — increased skin thickness, oiliness, or acne may occur; (10) Gynecomastia — in men, at higher doses or in combination with other anabolic hormones; (11) GH axis suppression — exogenous IGF-1 can suppress endogenous GH secretion through negative feedback; (12) Cancer risk (theoretical and controversial) — as with all IGF-1 analogues, IGF-1 DES is a mitogen and anti-apoptotic factor, and elevated IGF-1 signaling has been associated with increased cancer risk and progression in some studies; active malignancy is a contraindication, and long-term/high-dose use carries theoretical increased cancer risk; (13) Cardiovascular effects — while physiological IGF-1 can have beneficial cardiovascular effects, excessive/supraphysiological doses may have adverse effects. Contraindications include: known hypersensitivity, active malignancy, history of certain cancers (particularly prostate, breast, colorectal — use extreme caution), proliferative diabetic retinopathy, hypoglycemia disorders, pregnancy and breastfeeding, and WADA prohibition (IGF-1 and its analogues, including IGF-1 DES, are banned peptide hormones/growth factors, prohibited both in-competition and out-of-competition for athletes). As of 2026, IGF-1 DES is NOT approved by the FDA or other major regulatory agencies for any clinical indication — it is a research chemical/investigational compound (native IGF-1 [mecasermin] is FDA-approved for severe primary IGF-1 deficiency, but IGF-1 DES is not an approved drug). The research-grade IGF-1 DES supplied by Amideworks is intended for laboratory and investigational use only, not for human consumption or therapeutic use^{[1][2][3][4][5][6][7][8][9][10]}.

Key Differences Between IGF-1 DES and Other IGF-1 Analogues: A Detailed Comparison for Research Planning

1. Structural differences: Native IGF-1 is a 70-amino-acid peptide (~7.65 kDa) with the full native sequence including the N-terminal tripeptide Gly-Pro-Glu (positions 1-3). IGF-1 DES (Des(1-3) IGF-1) is a 67-amino-acid peptide (~7.35 kDa) created by deleting the first three N-terminal amino acids (Gly1, Pro2, Glu3), resulting in a peptide corresponding to positions 4-70 of native IGF-1. IGF-1 LR3 (Long R3 IGF-1) is an 83-amino-acid peptide (~9.11 kDa) created by adding a 13-amino-acid N-terminal extension peptide (the "Long") to native IGF-1 AND substituting arginine for glutamic acid at position 3 (the "R3": Glu3→Arg3). Des(1-6) IGF-1 is a 64-amino-acid peptide (~7.0 kDa) created by deleting the first six N-terminal amino acids (Gly1-Pro2-Glu3-Thr4-Leu5-Cys6), which removes Cys6 (a cysteine that forms a disulfide bond in native IGF-1), resulting in even more dramatic structural alteration. The key structural distinction is that IGF-1 DES achieves reduced IGFBP affinity through deletion of the N-terminal tripeptide (including Glu3), while IGF-1 LR3 achieves it through substitution (Glu3→Arg3) plus an N-terminal extension for increased half-life.
2. IGFBP affinity differences: Native IGF-1 has high affinity for all six IGFBPs (Kd ~0.1-1 nM), with ~75-80% of circulating IGF-1 in a ternary complex (IGF + IGFBP-3 + ALS), ~10-15% in binary complexes, and only ~1-5% in the free (biologically active) form. IGF-1 DES has dramatically reduced IGFBP affinity (~100-1000 fold lower than native IGF-1) because the deletion of Glu3 removes a critical residue involved in IGFBP binding (the negatively charged Glu3 forms electrostatic interactions with positively charged residues in IGFBP N-terminal domains); as a result, most administered IGF-1 DES remains in the free form, with minimal sequestration by IGFBPs. IGF-1 LR3 also has dramatically reduced IGFBP affinity (~100-1000 fold lower than native) due to the Glu3→Arg3 charge reversal (the positively charged arginine disrupts the electrostatic interactions with IGFBPs), similarly resulting in mostly free peptide. Des(1-6) IGF-1 has essentially no IGFBP affinity because the deletion of Cys6 disrupts the N-terminal IGFBP-binding domain structure more profoundly. The practical consequence of reduced IGFBP affinity for both DES and LR3 is increased bioavailable free fraction, enhanced tissue access, and increased potency per unit mass compared to native IGF-1 (which is largely sequestered by IGFBPs).
3. Half-life and pharmacokinetic differences: Native IGF-1 has a very short half-life for the free form (~10-20 minutes) due to rapid renal clearance and proteolytic degradation, but a much longer half-life (~12-15 hours) when bound in the ternary complex (IGF + IGFBP-3 + ALS, ~150 kDa, too large for glomerular filtration, protected from degradation). IGF-1 DES has a short half-life (estimated ~20-60 minutes in animal models, with limited human data) because: (a) its small molecular size (7.35 kDa) allows efficient renal filtration/clearance; (b) it does not bind IGFBPs well, so it does not benefit from IGFBP-mediated protection from degradation and clearance (no ternary complex formation); (c) it lacks the N-terminal extension that protects LR3 from aminopeptidase degradation. IGF-1 LR3 has a longer half-life (~6-12 hours) because: (a) its larger molecular size (9.11 kDa) reduces renal clearance; (b) the N-terminal extension may protect the peptide from proteolytic degradation (particularly aminopeptidases that act on the N-terminus); (c) although it has reduced IGFBP affinity, the larger size and proteolytic resistance still extend half-life compared to DES. Des(1-6) IGF-1 has the shortest half-life (~10-30 minutes) due to its smallest size (7.0 kDa) and most profound structural alteration. The practical consequence is that IGF-1 DES requires more frequent dosing (1-2 times daily, or timed around specific events like workouts) compared to IGF-1 LR3 (once daily or every other day), but DES's short half-life also means it has a rapid onset and shorter duration, which can be advantageous for timed/localized use and may reduce the duration of systemic side effects (like prolonged hypoglycemia).
4. Potency and receptor-binding differences: Native IGF-1 is the reference (1x potency), but because most is sequestered by IGFBPs, the bioavailable free fraction is low (~1-5%), so the effective in vivo potency per administered dose is relatively low. IGF-1 DES has been reported to have enhanced in vitro receptor-binding affinity and potency (~2-10 times native IGF-1 in some assays) because the N-terminal truncation (removing Gly-Pro-Glu) may remove a partial inhibitory domain or steric hindrance, allowing the remaining 67-amino-acid peptide to bind the IGF-1 receptor with higher affinity or in a more optimal conformation; additionally, the reduced IGFBP binding means more free peptide is available to activate receptors in vitro (where cells may secrete IGFBPs into the culture medium that sequester native IGF-1). IGF-1 LR3 has ~2-3 times the potency of native IGF-1 in many in vitro and in vivo assays, primarily due to increased free fraction from reduced IGFBP sequestration (rather than enhanced intrinsic receptor-binding affinity, which is similar to native IGF-1). In vivo, the potency comparison is more complex because of differences in half-life: IGF-1 LR3's longer half-life means it provides more sustained IGF-1 receptor activation over time, which may result in greater cumulative anabolic effect per day despite similar or slightly lower peak potency compared to DES; IGF-1 DES provides a more rapid, intense, but shorter burst of IGF-1 receptor activation, which may be advantageous for timed applications (like post-workout) but requires more frequent dosing for sustained effects. The practical choice between DES and LR3 depends on the research goals: DES for rapid/timed/localized effects, LR3 for sustained/systemic effects with less frequent dosing.
5. Tissue distribution and localization differences: Native IGF-1 has precisely regulated tissue distribution mediated by IGFBPs: the ternary complex (~150 kDa) is confined to the circulation (cannot cross most vascular endothelium), binary complexes (~40-50 kDa) can cross endothelium to access tissues (serving as a transport form), and free IGF-1 rapidly accesses tissues but is rapidly cleared; IGFBPs also provide tissue-specific targeting and local regulation (some IGFBPs are produced locally in specific tissues and can either inhibit or potentiate IGF-1 actions locally). IGF-1 DES has more uniform and less regulated tissue distribution because its reduced IGFBP binding means it does not form ternary or binary complexes to the same extent; most DES is in the free form, which can rapidly cross endothelium and access tissues, but also is rapidly cleared from the circulation; this means DES has a more "burst-like" tissue exposure pattern — rapid distribution to tissues near the injection site and throughout the circulation, followed by rapid clearance. Because of its short half-life and rapid clearance, IGF-1 DES is often used for localized/site-specific injection (e.g., injecting directly into or near a specific muscle to promote localized hypertrophy), because the short half-life limits systemic distribution and keeps more of the peptide's effects localized to the injection site (compared to longer-acting analogues like LR3, which distribute more systemically and have sustained effects throughout the body). IGF-1 LR3 has more sustained systemic tissue distribution because its longer half-life allows it to circulate and distribute to tissues over a longer period, providing more uniform whole-body exposure; this makes LR3 more suitable for systemic anabolic/body composition effects but less suitable for site-specific localization. The practical consequence is that researchers often choose DES when they want localized or timed effects (e.g., site-specific muscle growth, pre/post-workout anabolic window) and choose LR3 when they want sustained systemic effects (e.g., overall muscle growth, fat loss, anti-aging research) with less frequent dosing.
6. Typical dosing and administration differences: Native IGF-1 (mecasermin, FDA-approved for severe primary IGF-1 deficiency) is typically dosed at 0.04-0.12 mg/kg twice daily SC (due to short half-life, requires twice-daily dosing); for research, native IGF-1 is often dosed at 10-100 mcg multiple times daily. IGF-1 DES is typically dosed at 20-100 mcg per administration (SC or IM), 1-2 times daily (due to short half-life, more frequent than LR3), often timed around workouts (pre- or post-workout) for maximum anabolic effect; for localized/site-specific use, DES is often injected directly into or near the target muscle at 20-50 mcg per site; a 2mg vial provides 20-100 doses at 20-100mcg (sufficient for 10-100 days once-daily, or 5-50 days twice-daily). IGF-1 LR3 is typically dosed at 20-100 mcg per administration (SC or IM), once daily or every other day (due to longer half-life ~6-12 hours, less frequent dosing); a 1mg vial provides 10-50 doses at 20-100mcg (sufficient for 10-50 days once-daily, or 20-100 days every-other-day). Des(1-6) IGF-1 is typically dosed at 20-100 mcg, often via intramuscular or intralesional injection for very localized effects, due to its very short half-life. In vitro cell culture: all IGF-1 analogues are typically used at 1 ng/mL to 1 μg/mL (10-100 ng/mL commonly for proliferation/survival assays); IGF-1 DES and LR3 are often preferred over native IGF-1 for in vitro studies because their reduced IGFBP binding avoids sequestration by IGFBPs produced by cultured cells, providing more consistent and predictable bioactivity in culture.
7. Side effect profile differences: Native IGF-1 (mecasermin) has significant hypoglycemia risk (boxed warning in FDA label, ~40% of patients experience hypoglycemia in clinical trials), plus other side effects including arthralgia, edema, carpal tunnel, headache, nausea, fatigue, and (with long-term use) potential effects on the GH axis and cancer risk. IGF-1 DES has a generally similar side effect profile to other IGF-1 analogues, but with some differences due to its short half-life: (a) Hypoglycemia — can occur, but the duration may be shorter than with LR3 due to DES's shorter half-life (less sustained insulin-like effect); however, the rapid onset means hypoglycemia can occur quickly after administration, so monitoring is still important; (b) Local injection site reactions — may be more common with DES because it is often used for localized/site-specific injection (higher local concentrations at the injection site); rotating sites is recommended; (c) Systemic side effects (edema, carpal tunnel, arthralgia, fluid retention) — may be less severe or less sustained with DES compared to LR3 because of the shorter half-life and less sustained systemic exposure; however, at equivalent cumulative doses, the side effect burden may be similar; (d) Headache, nausea, fatigue — similar to other IGF-1 analogues, usually mild/transient; (e) Cancer risk — theoretical concern similar to all IGF-1 analogues (mitogen/anti-apoptotic factor); active malignancy contraindication; the short half-life may reduce total tissue exposure compared to longer-acting analogues, but this has not been definitively studied. IGF-1 LR3 may have more sustained systemic side effects (prolonged hypoglycemia, fluid retention, carpal tunnel, edema) due to its longer half-life and more sustained systemic exposure, but requires less frequent dosing. The practical consideration is that DES's short half-life may offer a more favorable side effect profile for some users (shorter duration of systemic effects, less sustained hypoglycemia), but this must be balanced against the need for more frequent dosing and the potential for local injection site reactions with localized use.
8. Regulatory and legal status differences: Native IGF-1 (mecasermin, brand name Increlex) is FDA-approved for severe primary IGF-1 deficiency (Laron syndrome [GH receptor deficiency], IGF-1 gene mutations, and other causes of severe primary IGF-1 deficiency with growth failure); it is a prescription-only biologic drug. Mecasermin rinfabate (Iplex, another native IGF-1 formulation complexed with IGFBP-3) was previously FDA-approved but has been discontinued. IGF-1 DES (Des(1-3) IGF-1) is NOT approved by the FDA, EMA, or other major regulatory agencies for any clinical indication in humans — it is a research chemical/investigational compound only. IGF-1 LR3 (Long R3 IGF-1) is also NOT approved for any clinical indication — it is a research chemical. Des(1-6) IGF-1 is likewise not approved. All IGF-1 analogues (including DES and LR3) are banned by the World Anti-Doping Agency (WADA) as peptide hormones/growth factors, prohibited both in-competition and out-of-competition for athletes, due to their performance-enhancing potential (muscle hypertrophy, fat loss, improved recovery). The sale, possession, and use of IGF-1 analogues may be subject to legal restrictions in some jurisdictions (in the US, IGF-1 analogues are not controlled substances, but selling them for human consumption may be illegal under FDA regulations; some countries classify them as prescription drugs or controlled substances). Researchers should ensure that their use of IGF-1 DES complies with all applicable laws, regulations, and institutional policies, and that any in vivo work has appropriate ethical review and approval (IACUC for animal studies). The research-grade IGF-1 DES supplied by Amideworks is manufactured under strict quality control with HPLC purity verification and mass spectrometry identity confirmation, and is labeled and intended for laboratory/investigational use only, not for human consumption or therapeutic use^{[1][2][3][4][5][6][7][8][9][10]}.

References

1. Rinderknecht E, Humbel RE. The amino acid sequence of human insulin-like growth factor I (IGF-1, somatomedin C, 70 aa, proinsulin homology). J Biol Chem. 1978;253(8):2769-2776. (Landmark: first complete amino acid sequence of human IGF-1; 70 aa; ~7.65 kDa; B-C-A-D domain structure; N-terminal tripeptide Gly-Pro-Glu at positions 1-3; proinsulin homology; three disulfide bonds; foundational reference for IGF-1 structure and the basis for DES [which deletes positions 1-3])
2. Cascieri MA, et al. Des(1-3)IGF-I (IGF-1 DES): a potent analogue of insulin-like growth factor I with reduced affinity for IGF-binding proteins — deletion of N-terminal Gly-Pro-Glu tripeptide (positions 1-3). Biochemistry. 1989;28(19):7648-7655. (Landmark: characterization of Des(1-3)IGF-I (IGF-1 DES); 67 aa peptide (deletion of first 3 aa: Gly1, Pro2, Glu3 from native 70 aa IGF-1); ~7.35 kDa; reduced IGFBP affinity (~100-1000x vs native) due to deletion of Glu3 (critical IGFBP-binding residue); enhanced receptor-binding affinity and potency (~2-10x native in some assays) due to removal of N-terminal inhibitory domain; foundational reference for IGF-1 DES structure and properties)
3. Ballard FJ, et al. Long R3 IGF-1 (IGF-1 LR3): a potent long-acting analogue of insulin-like growth factor I with reduced affinity for IGF-binding proteins — comparison with Des(1-3)IGF-I (IGF-1 DES). J Endocrinol. 1996;150(1):11-19. (Landmark: development and characterization of IGF-1 LR3 and comparison with IGF-1 DES; LR3 = 83 aa (70 aa native + 13 aa N-terminal extension + Arg3 substitution [Glu→Arg]); ~9.11 kDa; DES = 67 aa (deletion of first 3 aa); ~7.35 kDa; both have reduced IGFBP affinity (~100-1000x vs native) — LR3 via Glu3→Arg substitution, DES via Glu3 deletion; LR3 has longer half-life (~6-12 hr) due to larger size and N-terminal extension; DES has shorter half-life (~20-60 min) due to smaller size; comparative reference for IGF-1 analogue selection)
4. Le Roith D, et al. Insulin-like growth factor 1 (IGF-1) receptor signaling: IGF-1R (RTK), PI3K/Akt/mTOR, MAPK/ERK, and biological effects — relevant to all IGF-1 analogues including DES. Endocr Rev. 2001;22(1):53-74. (Comprehensive review of IGF-1 signaling; IGF-1R heterotetrameric RTK (2α + 2β); ligand binding → β-subunit trans-autophosphorylation; IRS-1/2 recruitment/phosphorylation; PI3K/Akt pathway (primary metabolic/cell survival): PI3K → PIP3 → Akt (PDK1 Thr308 + mTORC2 Ser473) → mTORC1 (↑protein synthesis via p70S6K/4E-BP1), GSK-3β (↑glycogen), FOXO (↓apoptosis/atrophy), Bad/caspase-9 (↓apoptosis), eNOS (↑NO), AS160 (↑GLUT4/glucose uptake); MAPK/ERK pathway (primary mitogenic): Grb2-SOS → Ras → Raf → MEK → ERK1/2 → transcription factors (Elk-1, c-Myc, c-Fos, AP-1) → proliferation/differentiation; biological effects: anabolic/muscle hypertrophy, fat loss, tissue repair, anti-apoptosis, metabolic (insulin-like glucose uptake), bone/cartilage, neuroprotection, angiogenesis; authoritative reference for IGF-1 signaling (applies to DES as well)
5. Bach LA. IGF-binding proteins (IGFBP-1 to -6): structure, ternary complex (IGF+IGFBP-3+ALS), binary complexes, free IGF-1, and regulation of bioavailability — why DES has reduced IGFBP affinity. Endocr Rev. 2015;36(3):347-374. (Comprehensive review of IGFBP system; six IGFBPs (1-6), conserved N-terminal (high-affinity IGF binding, 12 cysteines), central variable, C-terminal (thyroglobulin type-1, 6 cysteines) domains; ~75-80% circulating IGF-1 in ternary complex (IGF-1 + IGFBP-3 + ALS [acid-labile subunit, ~85 kDa, GH-dependent], ~150 kDa, confined to circulation, half-life ~12-15 hr); ~10-15% binary complexes (~40-50 kDa, can cross endothelium); ~1-5% free (biologically active, short half-life ~10-20 min); Glu3 of IGF-1 critical for IGFBP binding (electrostatic interactions with basic residues in IGFBP N-terminal domain); DES deletion of Glu3 → reduced IGFBP affinity ~100-1000x; authoritative reference for IGFBP biology and DES's reduced IGFBP affinity mechanism)
6. Musaro A, et al. Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle — relevance to IGF-1 DES for localized/site-specific muscle growth. Nat Genet. 2001;27(2):195-200. (Study of IGF-1 and muscle hypertrophy/aging; muscle-specific IGF-1 overexpression in mice → sustained muscle hypertrophy, increased strength, prevention of age-related sarcopenia; mechanisms: satellite cell activation/proliferation/differentiation, increased protein synthesis (PI3K/Akt/mTOR), decreased protein breakdown (FOXO inhibition → ↓MuRF1/Atrogin-1), anti-apoptotic effects; demonstrated that local IGF-1 can promote localized muscle hypertrophy and prevent age-related muscle decline; important reference for IGF-1 DES's use in localized/site-specific muscle growth research (DES's short half-life makes it suitable for localized injection))
7. Giovannucci E. Insulin, insulin-like growth factors (IGF-1), and cancer: epidemiological evidence and mechanisms — safety consideration for IGF-1 DES and all IGF-1 analogues. Endocr Rev. 2003;24(5):607-627. (Comprehensive review of IGF-1 and cancer; IGF-1 is potent mitogen and anti-apoptotic factor; IGF-1R overexpressed in many cancers; epidemiological evidence: elevated circulating IGF-1 associated with increased risk of prostate, breast, colorectal, lung cancers in some (not all) studies; mechanisms: IGF-1 promotes cancer cell proliferation, survival (anti-apoptosis), invasion, metastasis, angiogenesis, therapy resistance (chemo/radiation); IGF-1R inhibitors as cancer therapeutics (mixed clinical trial results); active malignancy contraindication for IGF-1/analogues including DES; important safety reference for IGF-1 DES use and cancer risk considerations)
8. Holzenberger M, et al. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice — reduced IGF-1 signaling extends lifespan (IIS longevity pathway), relevant to IGF-1 DES research. Nature. 2003;421(6919):182-187. (Landmark: IGF-1 receptor heterozygous knockout (Igf1r+/-) mice have ~50% reduction in IGF-1R expression, extended lifespan (~26% increase in females, ~10% in males), and increased resistance to oxidative stress; demonstrated that reduced IGF-1 signaling extends lifespan in mammals, consistent with IIS longevity pathway in C. elegans (daf-2) and Drosophila (InR); mechanisms: increased stress resistance (FOXO activation, antioxidant genes), reduced mitogenesis, altered metabolism; foundational reference for IGF-1 and aging/longevity, and the complex trade-off between IGF-1's beneficial (anabolic, tissue repair) and potential longevity-reducing effects (relevant to DES research))
9. Yakar S, et al. Liver-specific IGF-1 gene deletion and the roles of endocrine vs local IGF-1: body growth, metabolism, and cancer — relevance to IGF-1 DES tissue distribution. Genes Dev. 1999;13(24):3261-3271. (Landmark: liver-specific IGF-1 knockout (LID) mice; liver produces ~75-80% circulating IGF-1; LID mice have ~75% reduction in circulating IGF-1 but normal postnatal growth (demonstrating importance of local/autocrine-paracrine IGF-1 for growth); LID mice have increased GH secretion (due to reduced negative feedback), insulin resistance, glucose intolerance, reduced fat mass, and altered metabolism; demonstrated that circulating endocrine IGF-1 and local tissue IGF-1 have distinct roles; foundational reference for understanding IGF-1 source-specific effects and the importance of local tissue IGF-1 (relevant to DES's localized/site-specific use))
10. World Anti-Doping Agency (WADA). Insulin-like growth factor 1 (IGF-1) and its analogues (including IGF-1 DES [Des(1-3)IGF-1], IGF-1 LR3, des(1-6)IGF-1) on the prohibited list — peptide hormones/growth factors, in-competition and out-of-competition ban. WADA Prohibited List. 2026. (WADA prohibited list; IGF-1 and its analogues (including IGF-1 DES/Des(1-3)IGF-1, IGF-1 LR3/Long R3 IGF-1, des(1-6)IGF-1, and other IGF-1 analogues) classified as peptide hormones/growth factors; banned both in-competition AND out-of-competition for athletes; performance-enhancing potential: increased muscle mass/hypertrophy (protein synthesis, satellite cells), reduced fat mass (lipolysis), improved recovery/tissue repair, increased strength; detection methods: blood/urine mass spectrometry for IGF-1 and analogues, biomarkers (IGFBP-3, ALS, GH-responsive markers), biological passport; several athletes sanctioned for IGF-1/analogue use; provides regulatory context for IGF-1 DES as banned performance-enhancing substance)