DES(1-3) IGF-1

Research Reagent · Laboratory Use Only

What are the research findings on Des 1-3 IGF-1 and its potency compared to IGF-1?

Des 1-3 IGF-1 is a truncated analogue of insulin-like growth factor-1 lacking the first three N-terminal amino acids. Research indicates it binds IGF-1 receptors with approximately 10-fold greater potency than native IGF-1, due to reduced binding affinity for IGF-binding proteins. Preclinical studies explore its role in cellular proliferation and neuroprotection.

Scientific AbstractPMID 23106397 · 2013

Background

Although oral squamous cell carcinomas (OSCCs) commonly overexpress the epidermal growth factor receptor (EGFR), EGFR tyrosine kinase inhibitors (TKIs) exhibit poor efficacy clinically. Activation of the insulin-like growth factor-1 receptor (IGF1R) induces resistance of OSCC cells to EGFR-TKIs in vitro. This study seeks to evaluate the changes in cell cycle status in OSCC cells in response to gefitinib and IGF1R activation.

Methods

SCC-25 OSCC cells were used for in vitro analyses.

Results

Gefitinib caused a 50% reduction in S-phase population, and IGF1R activation caused a 2.8-fold increase; combined treatment yielded a baseline S-phase population. Gefitinib treatment increased the cyclin-dependent kinase inhibitor p27, and this was not abrogated by IGF1R activation. pT157-p27 was noted by immunoblot to be decreased on gefitinib treatment, but this was reversed with IGF1R activation. T157 phosphorylation contributes to cytoplasmic localization of p27 where it can promote cell proliferation and cell motility. Using both subcellular fractionation and immunofluorescence microscopy techniques, IGF1R stimulation was noted to increase the relative cytoplasmic localization of p27; this persisted when combined with gefitinib.

Conclusions

IGF1R activation partially reverses the cell cycle arrest caused by gefitinib in OSCC cells. While IGF1R stimulation does not eliminate the gefitinib-induced increase in total p27, its phosphorylation state and subcellular localization are altered. This may contribute to the ability of the IGF1R to rescue OSCC cells from EGFR-TKI treatment and may have important implications for the use of p27 as a biomarker of cell cycle arrest and response to therapy.

Mechanistic Research SummaryCurated from PubMed

This data is for laboratory research purposes only. Not for human or animal consumption.

What is DES(1-3) IGF-1?

DES(1-3) IGF-1 (also called Des(1-3)-IGF-1 or Long R3-IGF-1) is a synthetic analog of insulin-like growth factor-1 (IGF-1) that selectively activates the IGF-1 receptor (IGF1R) with reduced binding to insulin-like growth factor binding proteins (IGFBPs). In this research context, it was used as a pharmacological tool to study IGF1R-mediated resistance mechanisms in oral squamous cell carcinoma (OSCC) cells treated with EGFR tyrosine kinase inhibitors.

Mechanism of Action

DES(1-3) IGF-1 binds directly to IGF1R, triggering downstream activation of PI3K/AKT and MAPK/ERK signaling pathways. In OSCC cells, IGF1R activation antagonizes EGFR-TKI-induced cell cycle arrest by phosphorylating p27 (CDK inhibitor 1B) at the T157 residue, promoting cytoplasmic translocation of p27 and reducing its nuclear accumulation. This relocalization converts p27 from a cell cycle inhibitor to a promoter of cell proliferation and motility, effectively rescuing cancer cells from gefitinib-mediated growth suppression.

Observed Laboratory Results

  • S-phase population reversal: IGF1R activation via DES(1-3) IGF-1 induced a 2.8-fold increase in S-phase cells, reversing the 50% S-phase reduction caused by gefitinib monotherapy in SCC-25 OSCC cells.
  • p27 phosphorylation state alteration: Gefitinib decreased pT157-p27 levels, but concurrent IGF1R stimulation reversed this phosphorylation, enabling cytoplasmic sequestration of p27 despite elevated total p27 protein.
  • Subcellular p27 redistribution: Both subcellular fractionation and immunofluorescence microscopy demonstrated that DES(1-3) IGF-1 significantly increased cytoplasmic localization of p27, which persisted during combined gefitinib + IGF1R stimulation treatment.
Clinical Research Parameters
10 trials4 human studies

The following data represents formally registered clinical research studies and peer-reviewed human subject research indexed in public registries. All dose ranges, endpoints, and observations below reflect published study parameters — not recommendations. For research reference only.

ClinicalTrials.gov ↗
NCT05032326
UNKNOWNPhase IIIn=80

Long-term Interventional Follow-up Study of Children With Prader-Willi Syndrome Included in the OTBB3 Clinical Trial

This study is a prospective, multicentre, interventional cohort study in children with Prader-Willi Syndrome (PWS) over 4 years (no treatment administered). The duration of the preceding OTTB3 study is 26 weeks. An untreated cohort of children with PWS will be included at an age of 2 years and followed up until an age of 4 years. Regarding the untreated cohort, children with PWS born in France an

Study Interventions
Follow-up study of the treated cohort, Follow-up study of the untreated cohort
Primary Endpoints
Confirmation of the long term safety profile (1); Confirmation of the long term safety profile (2)
Study Period
2021-09-07 → 2025-04-01
NCT00163189
COMPLETEDPhase IIIn=98

Evolution Of Growth Rate In Children With Growth Retardation Due to Glucocorticosteroid Therapy And Treated By Genotonorm

To estimate the evolution of height and growth rate over 5 years of growth hormone (GH) treatment To estimate the prognostic factors of growth rate with GH treatment To confirm the good clinical and biological safety of GH treatment in such children

Study Interventions
Somatropin
Primary Endpoints
Change From Baseline in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Month 36: Full Analysis Population; Change From Baseline in Height Standard Deviation Score (SD) for Chronological Age (CA) at Month 36: Per Protocol (PP) Population
Study Period
2005-01 → 2014-12
NCT01431625
UNKNOWNPhase IVn=30

Effects of Exercise Training on Systemic Inflammation an Muscle Repair According to the Obstructive Chronic Pulmonary Disease (COPD) Phenotype

AIM: To identify those mechanisms involved in the systemic and muscular response to exercise treatment, in two different Obstructive Chronic Pulmonary Disease (COPD) phenotypes (emphysema and non-emphysema). The investigators will evaluate the effect of exercise training, on exercise outcomes, peripheral muscle strength measures, dyspnea and quality of life indices, and markers of systemic inflamm

Study Interventions
Combined Training (endurance and strength exercises)
Primary Endpoints
Change from baseline in TNF-alpha and its receptors, muscle isoforms of IGF-1 and its receptor in samples of quadriceps muscle satellite cells at 3 moths.
Study Period
2011-01 → 2012-12
NCT05028959
UNKNOWNN/An=80

Hormonal Status, Performance and Health in Elite Female Athlete

The repercussions of the hormonal status of high-level sportswomen on their performance and health as well as on the Athlete's Biological Passport (ABP) have been little studied and remain poorly known. The investigators therefore propose to contribute to the improvement of current knowledge by determining, thanks to the implementation of a multidisciplinary monitoring, with the use of various tes

Study Interventions
Multidisciplinary monitoring of healthy women
Primary Endpoints
Change from baseline weight; Change from baseline fat and lean mass
Study Period
2021-09-15 → 2025-05-31
NCT05163314
TERMINATEDPhase IIIn=352

A Study of Soticlestat as an Add-on Therapy in Children and Adults With Dravet Syndrome or Lennox-Gastaut Syndrome

The main aim of the study is to learn if soticlestat, when given as an add-on therapy, reduces the number of seizures in children and adults with Dravet Syndrome (DS) or Lennox-Gastaut Syndrome (LGS). Participants will receive their standard anti-seizure therapy, plus tablets of soticlestat. There will be scheduled visits and follow-up phone calls throughout the study.

Study Interventions
Soticlestat
Primary Endpoints
Number of Participants With At Least One Treatment Emergent Adverse Event (TEAE); Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Score
Study Period
2022-03-04 → 2025-09-24
NCT02616562
COMPLETEDPhase IIn=76

Investigating Efficacy and Safety of Once-weekly NNC0195-0092 Treatment Compared to Daily Growth Hormone Treatment (Norditropin® FlexPro®) in Growth Hormone Treatment naïve Pre-pubertal Children With Growth Hormone Deficiency

This trial is conducted globally. The aim of the trial is to investigate efficacy and safety of once-weekly NNC0195-0092 treatment compared to daily growth hormone treatment (Norditropin® FlexPro®) in growth hormone treatment naïve pre-pubertal children with growth hormone deficiency. The main trial period will consist of 26 weeks of treatment, followed by a 26 week extension period.

Study Interventions
somapacitan, Norditropin® FlexPro® pen
Primary Endpoints
Height Velocity (HV) (cm/Year) During the First 26 Weeks of Treatment, Measured as Standing Height With Stadiometer; Cohort II and Cohort III - Adverse Events Rate, Including Injection Site Reactions in Children With GHD.
Study Period
2016-03-31 → 2024-09-26
NCT00516698
COMPLETEDN/An=140

Changes in Breast Density and Blood Hormone Levels in Postmenopausal Women Receiving Anastrozole or Exemestane for Breast Cancer

RATIONALE: Studying changes in breast density and blood hormone levels in women receiving anastrozole or exemestane for breast cancer may help doctors learn more about the long-term effects of treatment and may help the study of breast cancer in the future. PURPOSE: This clinical trial is studying changes in breast density and blood hormone levels in postmenopausal women receiving anastrozole or

Study Interventions
polymorphism analysis, high performance liquid chromatography, laboratory biomarker analysis
Primary Endpoints
Changes in percent breast density in response to 1 year of aromatase inhibitor therapy; Changes in dense area in response to 1 year of aromatase inhibitor therapy
Study Period
2007-09 → 2009-12
NCT04530214
UNKNOWNN/An=130

Predictive Elements of Trauma and Its After-effects: Importance of the Quality of Neurobiological Response to Stress

The neurobiological response to stress is an adaptive response allowing us to cope with the multiple aggressions of daily life. This response orchestrates the body's systemic reaction. The intensity of response to stress can modify the body's functioning, which implies a variety of fields where biomarkers may be isolated: immunity, psychology, neurophysiology, integrative physiology. When stress i

Study Interventions
Blood collection, Saliva collection, Electrocardiography (ECG)
Primary Endpoints
Occurrence of depression; Occurrence of "psychosomatic death"
Study Period
2020-11-04 → 2023-05
NCT03811535
COMPLETEDPhase IIIn=200

A Research Study in Children With a Low Level of Hormone to Grow. Treatment is Somapacitan Once a Week Compared to Norditropin® Once a Day (REAL4)

The study compares 2 medicines for children who do not have enough hormone to grow: somapacitan given once a week (a new medicine) and Norditropin® given once a day (the medicine doctors can already prescribe). Researchers will test to see how well somapacitan works. The study will also test if somapacitan is safe. Participants will either get somapacitan or Norditropin® - which treatment particip

Study Interventions
Somapacitan, Norditropin®
Primary Endpoints
Height Velocity: In-trial Observation Period; Height Velocity: On-treatment Observation Period
Study Period
2019-05-20 → 2025-09-30
NCT04015141
RECRUITINGPhase IIn=100

A Study to Evaluate Efficacy and Safety of Perampanel Administered as an Adjunctive Therapy in Pediatric Participants With Childhood Epilepsy

The purpose of the study is to evaluate the efficacy of perampanel as measured by the 50 percent (%) responder rate during the maintenance period of the core study for seizure frequency in participants with pediatric epileptic syndrome (Cohort 1) and partial-onset seizures (POS) (Cohort 2).

Study Interventions
Perampanel Oral Suspension, Perampanel Tablet
Primary Endpoints
Proportion of 50% Responders For All Seizures During the Maintenance Period of Core Study
Study Period
2019-05-31 → 2027-12-23

All data presented on this page is for laboratory research purposes only. DES(1-3) IGF-1 is referenced here as a research reagent. This page does not constitute medical advice, clinical guidance, or endorsement of any compound for human or animal use. All referenced studies are available via PubMed (PMID: 23106397) and the DOI-linked journal publication. Researchers must consult applicable institutional and regulatory frameworks before conducting any protocols.