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Protein / target

Insulin-like growth factor 1

Encoded byIGF1P05019Homo sapiensSwiss-Prot
Clinical-stage
Therapeutic maturity
2
Clinical candidates
Small-molecule tractable
Druggability
Structure with Ligand
9
Research papers

Protein at a glance

Biological role

Insulin-like growth factor receptor binding

Strongest disease association

Microcephalic primordial dwarfism

Via encoding gene IGF1 · Genetic literature evidence · score 0.61

Therapeutic position

Clinically advancing target

Antibodies

Research activity

Emerging research

9 papers · latest 2024

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity.

View complete UniProt function annotation

The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. Stimulates glucose transport in bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake. May play a role in synapse maturation (PubMed:21076856, PubMed:24132240). Ca(2+)-dependent exocytosis of IGF1 is required for sensory perception of smell in the olfactory bulb (By similarity). Acts as a ligand for IGF1R. Binds to the alpha subunit of IGF1R, leading to the activation of the intrinsic tyrosine kinase activity which autophosphorylates tyrosine residues in the beta subunit thus initiating a cascade of down-stream signaling events leading to activation of the PI3K-AKT/PKB and the Ras-MAPK pathways. Binds to integrins ITGAV:ITGB3 and ITGA6:ITGB4. Its binding to integrins and subsequent ternary complex formation with integrins and IGFR1 are essential for IGF1 signaling. Induces the phosphorylation and activation of IGFR1, MAPK3/ERK1, MAPK1/ERK2 and AKT1 (PubMed:19578119, PubMed:22351760, PubMed:23243309, PubMed:23696648). As part of the MAPK/ERK signaling pathway, acts as a negative regulator of apoptosis in cardiomyocytes via promotion of STUB1/CHIP-mediated ubiquitination and degradation of ICER-type isoforms of CREM (By similarity)

Subcellular location

Secreted
Domains and Gene Ontology detail (85)

Gene Ontology

  • Calphav-beta3 integrin-IGF-1-IGF1R complex
  • Cexocytic vesicle
  • Cextracellular region
  • Cextracellular space
  • Cglutamatergic synapse
  • Cinsulin-like growth factor binding protein complex
  • Cinsulin-like growth factor ternary complex
  • Cneuronal dense core vesicle lumen
  • Cplatelet alpha granule lumen
  • Cpostsynapse
  • Fgrowth factor activity
  • Fhormone activity

195 aa · 22 kDa · 4 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Synaptic signallingUniProt · GOGrowth-factor signallingUniProt · GOCell proliferation & survivalGOCell migrationGOKinase signallingUniProt · GOTranscriptional regulationGO
View supporting evidence

Synaptic signalling

  • ·The insulin-like growth factors, isolated from plasma, are structurally and functionally…
  • ·glutamatergic synapse
  • ·postsynapse
  • ·postsynaptic modulation of chemical synaptic transmission

Growth-factor signalling

  • ·The insulin-like growth factors, isolated from plasma, are structurally and functionally…
  • ·insulin-like growth factor ternary complex
  • ·insulin-like growth factor receptor binding
  • ·insulin-like growth factor receptor signaling pathway

Cell proliferation & survival

  • ·cell population proliferation
  • ·positive regulation of cell population proliferation

Cell migration

  • ·positive regulation of cell migration
  • ·positive regulation of smooth muscle cell migration

Kinase signalling

  • ·The insulin-like growth factors, isolated from plasma, are structurally and functionally…
  • ·protein kinase activator activity
  • ·activation of protein kinase B activity
  • ·positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction

Transcriptional regulation

  • ·negative regulation of gene expression
  • ·positive regulation of DNA-templated transcription
  • ·positive regulation of gene expression
  • ·positive regulation of transcription by RNA polymerase II

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene IGF1

Gene-level evidence surfaced through the gene IGF1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

COVID-19
0.61Moderately supported

Genetic evidence dominant · Open Targets 0.36

Breast Neoplasms
0.56Moderately supported

Genetic evidence dominant · Open Targets 0.29

Microcephalic primordial dwarfism
0.56Moderately supported

Genetic literature evidence dominant · Open Targets 0.38

Pre-Eclampsia
0.55Moderately supported

Genetic evidence dominant · Open Targets 0.32

View evidence synthesis (4)
COVID-19Moderately supported
0.61
agreement 0.470.75
Genetic81%Literature19%

Open Targets aggregate 0.36 · 2 independent evidence families

Breast NeoplasmsModerately supported
0.56
agreement 0.460.67
Genetic59%Literature21%Clinical19%

Open Targets aggregate 0.29 · 3 independent evidence families

Microcephalic primordial dwarfismModerately supported
0.56
agreement 0.430.69
Genetic literature77%Animal model20%Literature3%

Open Targets aggregate 0.38 · 3 independent evidence families

Pre-EclampsiaModerately supported
0.55
agreement 0.410.69
Genetic87%Literature13%

Open Targets aggregate 0.32 · 2 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Microcephalic primordial dwarfism0.38
COVID-190.36
Pre-Eclampsia0.32
Breast Neoplasms0.29

Drug development

2 compounds recorded · 2 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines.

View all recorded compounds (2)
XENTUZUMABPhase 2
DUSIGITUMABPhase 2

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesEmerging

Feasibility evidence (structure with ligand and med-quality pocket) — no clinical-stage drug of this modality recorded.

AntibodiesStrong

Advanced Clinical and GO CC high conf support this modality.

Protein degradersEmerging

Feasibility evidence (database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (7)
SM · Structure with LigandSM · Med-Quality PocketAB · Advanced ClinicalAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Database Ubiquitination

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

regulation of transcription factor activityToxCast

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Research activity

9 papers · to 2024

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Trejo JL · The Journal of neuroscience : the official journal of the Society for Neuroscience · 2001

Aberg MA · The Journal of neuroscience : the official journal of the Society for Neuroscience · 2000

Carro E · The Journal of neuroscience : the official journal of the Society for Neuroscience · 2000

Recent

SEP-363856 attenuates CUMS-induced depression-like behaviours and reverses hippocampal neuronal injuries.

Li M · The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry · 2024

Cancer in growth hormone excess and growth hormone deficit.

Guevara-Aguirre J · Endocrine-related cancer · 2023

The gut microbiota influences skeletal muscle mass and function in mice.

Lahiri S · Science translational medicine · 2019

Circulating insulin-like growth factor I mediates exercise-induced increases in the number of new neurons in the adult hippocampus.

Trejo JL · The Journal of neuroscience : the official journal of the Society for Neuroscience · 2001

Circulating insulin-like growth factor I mediates effects of exercise on the brain.

Carro E · The Journal of neuroscience : the official journal of the Society for Neuroscience · 2000

Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus.

Aberg MA · The Journal of neuroscience : the official journal of the Society for Neuroscience · 2000

Europe PMC papers linked directly to this protein.