IGF-1 DES [Peptide]

Description

What is IGF-1 DES?

IGF-1 DES  formally designated des(1-3)IGF-1  is a naturally occurring, endogenous truncated analog of insulin-like growth factor 1 (IGF-1). It is produced through N-terminal proteolytic processing of full-length IGF-1 and lacks the first three amino acid residues (Gly-Pro-Glu) present at the N-terminus of the 70-amino acid parent molecule. The result is a 67-amino acid polypeptide that retains the three-disulfide bond framework, the receptor-binding domains, and the C-domain architecture of native IGF-1, while exhibiting markedly reduced affinity for insulin-like growth factor-binding proteins (IGFBPs)  particularly IGFBP-1, -2, and -3.

In research settings, IGF-1 DES has been widely employed as a pharmacological tool for investigating IGF-1 receptor (IGF-1R) signaling independent of IGFBP-mediated regulation. It has been investigated in preclinical models and in vitro systems for its roles in IGF-1R-PI3K-Akt pathway activation, Ras-MAPK/ERK cascade engagement, satellite cell proliferation in myogenic preparations, and retinal IGF-1R regulation in diabetic rodent models.

IGF-1 DES supplied by RCDbio is intended strictly for laboratory and research purposes. It is not approved by the Food and Drug Administration for use in this research-grade, non-pharmaceutical form. It is not a dietary supplement and is not intended for human consumption or therapeutic self-administration.

Chemical Properties

Property	Detail
Product Type	Synthetic Truncated Polypeptide Analog (IGF-1 N-terminal des(1-3) variant)
Product Name	IGF-1 DES (des(1-3)IGF-1; 4-70-Insulin-Like Growth Factor 1)
Application	Scientific / Research Use Only
CAS Number	112603-35-7
Molar Mass	7365.42 g/mol
Chemical Formula	C₃₁₉H₄₉₅N₉₁O₉₆S₇
Sequence	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-Ala-Ala-Lys-Ser-Ala (67 residues; N-terminus starts at Thr-4 of native IGF-1; three intramolecular disulfide bonds preserved)
IUPAC Name	Full systematic IUPAC designation of the 67-residue polypeptide chain; refer to PubChem CID 135331146 for complete canonical notation
Synonyms	des(1-3)IGF-1; des(1-3) Insulin-Like Growth Factor 1; 4-70-IGF-1; Truncated IGF-1
Physical Form	Lyophilized white to off-white powder
Solubility	Soluble in sterile bacteriostatic water or dilute acetic acid (0.1–1% v/v); reconstitute immediately before use; avoid alkaline conditions which may disrupt disulfide integrity
Storage (Lyophilized)	Store at −20°C in a sealed, light-protected container with desiccant; protect from moisture and freeze-thaw cycling prior to reconstitution
Storage (Reconstituted)	Store at 4°C; use within 24–48 hours of reconstitution; for extended in vitro storage protocols, −80°C may be used with minimal freeze-thaw cycling; discard any solution showing turbidity, particulate matter, or discoloration
PubChem CID	135331146
Purity	≥98% (HPLC verified, independent third-party laboratory analysis; COA available per batch)
WADA Status	IGF-1 and its analogs — explicitly including des(1-3)IGF-1 — are prohibited at all times under WADA Prohibited List Section S2.3 (Growth Factors and Growth Factor Modulators). This prohibition applies in-competition and out-of-competition regardless of dosage or source. Researchers engaged in sport-adjacent studies should verify current status at GlobalDRO.com before use.

How Does IGF-1 DES Work?

IGF-1 DES engages the insulin-like growth factor 1 receptor (IGF-1R), a receptor tyrosine kinase (RTK) expressed across most mammalian tissues, with maintained affinity comparable to native IGF-1. The critical mechanistic distinction of IGF-1 DES from full-length IGF-1 lies not in its receptor-binding capacity, but in its dramatically reduced interaction with IGFBPs — the carrier proteins that sequester and regulate the bioavailability of circulating IGF-1. Deletion of the N-terminal Gly-Pro-Glu tripeptide reduces IGFBP-3 binding affinity by approximately 25-fold and IGFBP-1 affinity more substantially, effectively freeing a greater proportion of the analog for direct receptor engagement in in vitro and in vivo experimental systems. The following subheadings describe the principal downstream molecular pathways characterized in preclinical and in vitro systems following IGF-1R activation.

IGF-1R Tyrosine Kinase Activation and IRS/Shc Substrate Phosphorylation

In isolated cell preparations and mammalian cell-free systems, ligand binding of IGF-1 DES to the extracellular α-subunit of IGF-1R induces a conformational change in the transmembrane β-subunit, activating the intracellular receptor tyrosine kinase domain. Activated IGF-1R autophosphorylates and subsequently phosphorylates intracellular substrates including insulin receptor substrates (IRS-1, IRS-2) and the Src homology collagen (Shc) adaptor protein. Phosphotyrosine residues on these substrates serve as docking sites for SH2 domain-containing signaling molecules, initiating the two primary downstream signaling cascades observed in IGF-1R biology.

PI3K-Akt-mTOR Pathway

In a broad range of mammalian cell line preparations — including neuronal, myogenic, and epithelial in vitro systems — phosphorylated IRS-1 recruits the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3K), activating PI3K’s catalytic activity. PI3K-mediated conversion of PIP2 to PIP3 activates PDK1, which phosphorylates Akt (threonine 308); mTORC2 subsequently phosphorylates Akt at serine 473, producing fully activated Akt. Downstream Akt substrates include mTOR (promoting protein synthesis), BAD (anti-apoptotic inactivation), and FOXO transcription factors (cell cycle regulation). This cascade has been characterized as the primary pro-survival and anabolic signaling arm of IGF-1R activation in isolated cell preparations.

Ras-MAPK/ERK Pathway

In parallel to PI3K activation, phosphorylated IRS-1 and Shc recruit Grb2/SOS adaptor complexes, initiating GDP-to-GTP exchange on Ras GTPase. Activated Ras engages the Raf/MEK/ERK kinase cascade, resulting in ERK1/2 phosphorylation and nuclear translocation. ERK-mediated phosphorylation of transcriptional activators has been characterized in mammalian cell preparations as the primary mechanism by which IGF-1R signaling promotes DNA synthesis and mitogenic responses. In preclinical in vitro models using MEK-specific inhibitors (PD98059, U0126), MAPK pathway activation has been shown to be required for IGF-1-induced cell proliferation across multiple cell types.

Retinal IGF-1R Regulation in Diabetic Rodent Models

In streptozotocin (STZ)-induced diabetic rat preparations, des(1-3)IGF-1 administration has been investigated for its effects on IGF-1R and phospho-Akt (Thr308) immunoreactivity in predegenerative retinal tissue. Systemic des(1-3)IGF-1 treatment in STZ diabetic rats was associated with normalization of aberrant IGF-1R and phospho-Akt accumulations in the inner nuclear layer (INL) and ganglion cell layer (GCL), observations that were noted to occur independently of glycemic correction in the experimental model. These findings are derived exclusively from in vivo rodent model systems and do not represent human mechanistic data for research-grade material.

Key Research Findings

• Reduced IGFBP affinity and enhanced receptor availability: des(1-3)IGF-1 exhibits approximately 25-fold reduced binding to IGFBP-3 relative to native IGF-1, characterized in biosensor binding assays; this structural difference is mechanistically attributed to disruption of backbone interactions at the N-terminal interface in carrier protein binding studies. [Bagley et al., 1989; Heding et al.]

• IGF-1R-PI3K-Akt engagement in neocortical preparations: des(1-3)IGF-1 activation of the IGF-1R-PI3K-Akt and IGF-1R-Ras-ERK signaling cascades characterized in murine neocortical tissue preparations; Akt phosphorylation blocked by selective IGF-1R antagonist picropodophyllin (PPP) and by AAV-Cre-mediated IGF-1R knockdown, confirming IGF-1R-dependent mechanism. [preclinical in vivo murine preparations]

• Retinal predegenerative biomarker normalization: Systemic des(1-3)IGF-1 treatment in STZ diabetic rats significantly reduced aberrant IGF-1R and phospho-Akt (Thr308) immunoreactivity in INL and GCL; observed in the absence of hyperglycemia correction, suggesting receptor-level effect independent of metabolic normalization. [Kummer et al., 2003]

• IGF-1R downstream PI3K pathway review: IGF-1 ligand binding to IGF-1R characterized as initiating dual PI3K-Akt and Ras-MAPK cascades in mammalian cell preparations; MAPK pathway activation required for DNA synthesis induction across multiple cell types as demonstrated with MEK inhibitor experiments. [Hakuno & Takahashi, 2018]

• Anterior pituitary GH/IGFBP secretion modulation: des(1-3)IGF-1 investigated as a potent IGF analog in cultured rat anterior pituitary cell preparations; differential effects on growth hormone and IGFBP secretion relative to native IGF-1 and IGF-II characterized in in vitro pituitary cell system. [Simes et al., 1991; PMID 1715381]

All findings listed above are derived from preclinical or in vitro data. No conclusions regarding human therapeutic efficacy can be drawn from these observations. These findings do not constitute evidence of safety or efficacy in any human condition or organism.

What are the Potential Research Applications of IGF-1 DES?

IGF-1R Signaling Pathway Studies Independent of IGFBP Interference

IGF-1 DES is used in in vitro cell culture systems and ex vivo tissue preparations as a mechanistic tool to investigate IGF-1R signaling in conditions that minimize the confounding contribution of endogenous IGFBP modulation. Because the truncation dramatically reduces IGFBP binding, IGF-1 DES-based assay systems allow researchers to study IGF-1R-PI3K-Akt and IGF-1R-Ras-MAPK pathway activation with greater predictability of effective ligand concentration relative to full-length IGF-1 preparations in IGFBP-rich biological matrices.

Comparative IGF Analog Pharmacology

In receptor binding kinetics, displacement assay, and IGFBP affinity studies, IGF-1 DES serves as a structurally defined reference analog for characterizing the contribution of the N-terminal Gly-Pro-Glu tripeptide to IGF-1’s interaction landscape. Side-by-side comparison of des(1-3)IGF-1 with native IGF-1 and IGF-1 LR3 in cell-free binding assays allows researchers to isolate the mechanistic significance of N-terminal residues and IGFBP interaction in receptor engagement and downstream pathway activation.

Myogenic and Satellite Cell Research Models

In rodent skeletal muscle preparation and isolated myoblast in vitro studies, IGF-1 DES has been employed to investigate IGF-1R-mediated effects on satellite cell responses and myogenic signaling. The compound’s reduced IGFBP sequestration in interstitial experimental environments makes it a research tool for studying localized IGF-1R activation in muscle tissue preparations under conditions that approximate IGFBP-limited availability of full-length IGF-1 in situ.

Retinal and Neuroprotective Signaling Research

In rodent diabetic retinopathy models and neuronal in vitro preparations, IGF-1 DES has been used to probe IGF-1R signaling in predegenerative retinal tissue and in models of neurotrophic factor deprivation. Its application in these systems allows investigation of IGF-1R pathway activity and downstream Akt phosphorylation states in tissues relevant to neurodegenerative and metabolic disease preclinical models.

IGFBP Biology and Binding Protein Interaction Studies

IGF-1 DES is employed in in vitro biosensor and competitive binding assay systems as a reference ligand for characterizing IGFBP binding interfaces. Its defined, reduced-affinity interaction profile with IGFBP-1, -2, and -3 makes it a structurally informative comparator in studies mapping the molecular determinants of IGF/IGFBP interaction specificity across the IGFBP family.

These are observed in preclinical and in vitro contexts only and do not constitute claims of efficacy or safety in any organism.

What are the Potential Side Effects of IGF-1 DES?

• Hypoglycemia-like effects have been observed in rodent in vivo models at supraphysiological doses of IGF-1 and related analogs, consistent with partial insulin receptor (IR) cross-reactivity; these effects are dose-dependent and not uniform across rodent species or dosing conditions
• In in vitro transformed cell preparations, IGF-1R pathway activation by IGF-1 analogs has been associated with enhanced cell survival and proliferation signaling; this is a pharmacological consequence of IGF-1R engagement and is relevant to assay design in cancer cell model systems
• Injection-site tissue reactions have been reported in rodent subcutaneous administration models of IGF-1 analogs at high local concentrations; these are model- and dose-dependent and do not reflect systemic compound toxicity
• In preclinical pituitary cell preparations, des(1-3)IGF-1 has been associated with modulation of growth hormone and IGFBP secretion; these observations are relevant to assay interpretation in neuroendocrine research systems that include pituitary-derived cell components

No human safety or tolerability data pertaining to research-grade IGF-1 DES has been established. These observations are derived from experimental systems and should not be extrapolated to human or animal outcomes.

Risk & Handling

Risk Tier: MODERATE

IGF-1 DES is a potent, endogenous polypeptide with well-characterized pharmacological activity at IGF-1R in peripheral and central tissues. At research-relevant concentrations, it is not acutely toxic in preclinical systems; however, its enhanced bioavailability relative to native IGF-1 (due to reduced IGFBP sequestration) means that effective IGF-1R engagement occurs at lower concentrations than required with full-length IGF-1 in IGFBP-rich systems. Dose-dependent hypoglycemic and mitogenic effects have been observed in rodent in vivo models at supraphysiological concentrations. No human safety data has been established for research-grade material.

Handling Precautions

Handling of IGF-1 DES lyophilized powder and reconstituted solutions must be performed by trained laboratory personnel only. Personal protective equipment (PPE) should include nitrile gloves, a laboratory coat, and eye protection at minimum. Lyophilized powder should be reconstituted in a laminar flow biosafety cabinet to minimize particulate contamination and maintain aseptic technique. The compound contains three intramolecular disulfide bonds — avoid exposure to reducing agents (DTT, β-mercaptoethanol, TCEP) which will disrupt disulfide bridge integrity and inactivate the compound. Avoid reconstitution under strongly alkaline conditions (pH > 8.0) for the same reason.

Exposure Risks

IGF-1 DES is pharmacologically active at IGF-1R at research-relevant concentrations. Unintended parenteral or mucosal exposure in laboratory settings should be avoided. The compound’s partial insulin receptor cross-reactivity means that systemic exposure at high concentrations could theoretically engage IR-mediated glucose uptake pathways, though no acute hazard from standard laboratory contact exposure has been documented. No human safety data has been established for research-grade IGF-1 DES. Standard precautions appropriate to handling a potent biologically active recombinant polypeptide apply throughout.

Storage

• Lyophilized form: Store at −20°C in a sealed, light-protected container with desiccant; do not subject to repeated freeze-thaw cycles prior to reconstitution
• Reconstituted form: Store at 4°C; use within 24–48 hours of reconstitution; for extended storage in in vitro protocols, −80°C is preferred with single-use aliquots to avoid repeated freeze-thaw cycling
• Do not reconstitute in the presence of reducing agents; DTT, β-mercaptoethanol, or TCEP will cleave the three intramolecular disulfide bonds and irreversibly inactivate the compound
• Avoid alkaline reconstitution buffers (pH > 8.0); dilute acetic acid (0.1–1% v/v) or sterile bacteriostatic water at physiological pH is preferred
• Discard any reconstituted solution that appears turbid, discolored, or shows particulate matter

FAQs

Q: What is IGF-1 DES and what is it investigated for in research?

A: IGF-1 DES (des(1-3)IGF-1) is a naturally occurring, endogenous 67-amino acid truncated analog of IGF-1, lacking the N-terminal Gly-Pro-Glu tripeptide of the parent molecule. In laboratory research, it is investigated as a pharmacological tool for studying IGF-1R-mediated signaling — particularly the PI3K-Akt and Ras-MAPK cascades — under conditions of minimized IGFBP-mediated modulation. It is supplied by RCDbio for use in preclinical and in vitro research systems only and is not intended for human use or therapeutic self-administration.

Q: How does the N-terminal truncation in IGF-1 DES affect its interaction with IGF-binding proteins?

A: The deletion of the Gly-Pro-Glu N-terminal tripeptide in des(1-3)IGF-1 disrupts a critical binding interface — specifically backbone contacts — with insulin-like growth factor binding proteins, reducing IGFBP-3 affinity approximately 25-fold relative to native IGF-1 as characterized in in vitro biosensor binding assays. Affinity for IGFBP-1 is reduced more substantially. Because IGFBPs sequester and limit the free fraction of IGF-1 available for receptor engagement, the truncation results in a greater proportion of the peptide being available for IGF-1R binding in IGFBP-rich experimental matrices.

Q: What is the half-life of IGF-1 DES in preclinical models?

A: The plasma half-life of IGF-1 DES in rodent in vivo models is considerably shorter than that of native IGF-1, primarily because native IGF-1’s extended half-life (hours to days) depends on IGFBP-mediated protection from proteolytic clearance. IGF-1 DES, with its reduced IGFBP affinity, is more rapidly cleared from circulation in experimental animal models. Precise half-life values are assay- and model-dependent. These figures are derived from preclinical rodent data and do not represent human pharmacokinetic information for research-grade material.

Q: How should IGF-1 DES be stored to maintain stability?

A: Lyophilized IGF-1 DES should be stored at −20°C in a sealed container with desiccant, protected from light, moisture, and repeated freeze-thaw cycling. Upon reconstitution, solutions should be stored at 4°C and used within 24–48 hours, or stored as single-use aliquots at −80°C to minimize freeze-thaw-related degradation. Reducing agents (DTT, β-mercaptoethanol, TCEP) must be excluded from all reconstitution and storage buffers, as they will cleave the three intramolecular disulfide bonds and irreversibly inactivate the compound.

Q: What is IGF-1 DES typically reconstituted with in laboratory research?

A: In laboratory settings, IGF-1 DES is most commonly reconstituted in sterile bacteriostatic water or dilute acetic acid (0.1–1% v/v) to produce a stock solution. The use of acetic acid at low concentrations helps maintain peptide solubility and stability. Reconstituted stock solutions are typically diluted into phosphate-buffered saline (PBS) or culture medium immediately before use in cell-based assay systems. Alkaline buffers (pH > 8.0) should be avoided, as they may promote disulfide bond disruption.

Q: What toxicity observations have been reported in preclinical studies of IGF-1 DES?

A: IGF-1 DES itself has not been independently associated with acute organ toxicity in preclinical models at research-relevant concentrations. Its pharmacological profile — including dose-dependent hypoglycemia-like effects at supraphysiological doses and partial IR cross-reactivity — is consistent with the broader class of IGF-1 analogs in rodent in vivo studies. Enhanced potency relative to native IGF-1 in IGFBP-rich systems is a design characteristic, not a safety signal, but researchers should account for this when translating concentrations between in vitro and in vivo preclinical assay designs.

Q: Is IGF-1 DES prohibited under WADA anti-doping regulations?

A: Yes. IGF-1 and its analogs — a category that explicitly includes des(1-3)IGF-1 — are prohibited at all times under WADA Prohibited List Section S2.3, Growth Factors and Growth Factor Modulators. This prohibition applies in-competition and out-of-competition regardless of dosage, route, or source of the compound. Researchers engaged in sport-adjacent studies, anti-doping research, or studies requiring knowledge of an athlete’s supplement/compound use should verify current status at GlobalDRO.com and consult the authoritative WADA Prohibited List before conducting research involving this compound.

Related Research Compounds

IGF-1 LR3: A long-acting synthetic IGF-1 analog featuring an arginine substitution at position 3 and a 13-amino acid N-terminal extension; exhibits similarly reduced IGFBP affinity to IGF-1 DES but with a substantially extended plasma half-life, making it a comparator of choice in preclinical studies examining duration-of-exposure effects on IGF-1R-mediated signaling.

IGF-1: The full-length 70-amino acid endogenous parent peptide; employed as the primary reference ligand in IGF-1R binding displacement assays and as a mechanistic control in preclinical studies where IGFBP-regulated bioavailability is the experimental variable of interest.

MGF (Mechano Growth Factor): A splice variant of IGF-1 with a distinct C-terminal extension; investigated in preclinical models of skeletal muscle satellite cell activation in response to mechanical load; mechanistically distinct from IGF-1 DES but employed in related myogenic research contexts as a comparator ligand.

References

1. Hakuno F, Takahashi SI. IGF1 receptor signaling pathways. J Mol Endocrinol. 2018;61(1):T69–T86. https://pubmed.ncbi.nlm.nih.gov/29535161/
   
2. Kummer A, Pulford BE, Ishii DN, Seigel GM. Des(1–3)IGF-1 treatment normalizes type 1 IGF receptor and phospho-Akt (Thr 308) immunoreactivity in predegenerative retina of diabetic rats. Exp Diabesity Res. 2003;4(1):45–57. https://pubmed.ncbi.nlm.nih.gov/12745670/
   
3. Simes JM, Wallace JC, Walton PE. The effects of IGF-I, IGF-II and des(1-3)IGF-I, a potent IGF analogue, on growth hormone and IGF-binding protein secretion from cultured rat anterior pituitary cells. J Endocrinol. 1991;130(1):93–99. https://pubmed.ncbi.nlm.nih.gov/1715381/
   
4. Baserga R. The IGF-I receptor in cancer research. Exp Cell Res. 1999;253(1):1–6. https://pubmed.ncbi.nlm.nih.gov/10579905/
   
5. Gallagher EJ, LeRoith D. The proliferating role of insulin and insulin-like growth factors in cancer. Trends Endocrinol Metab. 2010;21(10):610–618. https://pubmed.ncbi.nlm.nih.gov/20663687/
   

Disclaimer 

IGF-1 DES is exclusively for laboratory research purposes. RCDbio products are not intended to diagnose, prevent, treat, or cure any disease or medical condition.

The Food and Drug Administration has not evaluated the statements on our website. This product is not approved for human or veterinary use. Researchers must comply with all applicable local, state, and federal laws and regulations governing the purchase and use of research compounds. By purchasing, you agree to our Terms and Conditions. RCDbio reserves the right to refuse sales to unauthorized individuals.

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