Target Information
| Target General Information | Top | |||||
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| Target ID |
T60930
(Former ID: TTDI02228)
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| Target Name |
Insulin-like growth factor-I (IGF1)
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| Synonyms |
SomatomedinC; Somatomedin-C; Mechano growth factor; Insulin-like growth factor I; IGFI; IGF-I
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| Gene Name |
IGF1
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 3 Target-related Diseases | + | ||||
| 1 | Breast cancer [ICD-11: 2C60-2C6Y] | |||||
| 2 | Prostate cancer [ICD-11: 2C82] | |||||
| 3 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
| Function |
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. Ca(2+)-dependent exocytosis of IGF1 is required for sensory perception of smell in the olfactory bulb. 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 initiatiating 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. The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity.
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| UniProt ID | ||||||
| Sequence |
MGKISSLPTQLFKCCFCDFLKVKMHTMSSSHLFYLALCLLTFTSSATAGPETLCGAELVD
ALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSARS VRAQRHTDMPKTQKYQPPSTNKNTKSQRRKGWPKTHPGGEQKEGTEASLQIRGKKKEQRR EIGSRNAECRGKKGK Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| ADReCS ID | BADD_A03920 | |||||
| HIT2.0 ID | T80R6A | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | Xentuzumab | Drug Info | Phase 2 | Breast cancer | [2] | |
| 2 | BI-836845 | Drug Info | Phase 1 | Solid tumour/cancer | [3] | |
| 3 | MEDI-573 | Drug Info | Phase 1 | Solid tumour/cancer | [4], [5] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | BI-836845 | Drug Info | [6] | |||
| 2 | MEDI-573 | Drug Info | [7] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Deoxy-Bigchap | Ligand Info | |||||
| Structure Description | 1.8 Angstrom crystal structure of IGF-1 | PDB:1IMX | ||||
| Method | X-ray diffraction | Resolution | 1.82 Å | Mutation | No | [8] |
| PDB Sequence |
ETLCGAELVD
12 ALQFVCGDRG22 FYFNKPTGYG32 SSTGIVDECC48 FRSCDLRRLE58 MYCAPL |
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| MAPK signaling pathway | hsa04010 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Ras signaling pathway | hsa04014 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Rap1 signaling pathway | hsa04015 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| HIF-1 signaling pathway | hsa04066 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| FoxO signaling pathway | hsa04068 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Oocyte meiosis | hsa04114 | Affiliated Target |
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| Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
| p53 signaling pathway | hsa04115 | Affiliated Target |
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| Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
| mTOR signaling pathway | hsa04150 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| PI3K-Akt signaling pathway | hsa04151 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| AMPK signaling pathway | hsa04152 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Longevity regulating pathway | hsa04211 | Affiliated Target |
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| Class: Organismal Systems => Aging | Pathway Hierarchy | ||
| Longevity regulating pathway - multiple species | hsa04213 | Affiliated Target |
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| Class: Organismal Systems => Aging | Pathway Hierarchy | ||
| Focal adhesion | hsa04510 | Affiliated Target |
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| Class: Cellular Processes => Cellular community - eukaryotes | Pathway Hierarchy | ||
| Signaling pathways regulating pluripotency of stem cells | hsa04550 | Affiliated Target |
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| Class: Cellular Processes => Cellular community - eukaryotes | Pathway Hierarchy | ||
| Long-term depression | hsa04730 | Affiliated Target |
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| Class: Organismal Systems => Nervous system | Pathway Hierarchy | ||
| Inflammatory mediator regulation of TRP channels | hsa04750 | Affiliated Target |
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| Class: Organismal Systems => Sensory system | Pathway Hierarchy | ||
| Ovarian steroidogenesis | hsa04913 | Affiliated Target |
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| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Progesterone-mediated oocyte maturation | hsa04914 | Affiliated Target |
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| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Growth hormone synthesis, secretion and action | hsa04935 | Affiliated Target |
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| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Aldosterone-regulated sodium reabsorption | hsa04960 | Affiliated Target |
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| Class: Organismal Systems => Excretory system | Pathway Hierarchy | ||
| Click to Show/Hide the Information of Affiliated Human Pathways | |||
| Degree | 43 | Degree centrality | 4.62E-03 | Betweenness centrality | 4.88E-03 |
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| Closeness centrality | 2.56E-01 | Radiality | 1.44E+01 | Clustering coefficient | 1.20E-01 |
| Neighborhood connectivity | 3.79E+01 | Topological coefficient | 4.71E-02 | Eccentricity | 11 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| PID Pathway | [+] 6 PID Pathways | + | ||||
| 1 | Plasma membrane estrogen receptor signaling | |||||
| 2 | SHP2 signaling | |||||
| 3 | IGF1 pathway | |||||
| 4 | Ceramide signaling pathway | |||||
| 5 | Integrins in angiogenesis | |||||
| 6 | Stabilization and expansion of the E-cadherin adherens junction | |||||
| References | Top | |||||
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| REF 1 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 2 | ClinicalTrials.gov (NCT03659136) The XENERA 1 Study Tests Xentuzumab in Combination With Everolimus and Exemestane in Women With Hormone Receptor Positive and HER2-negative Breast Cancer That Has Spread. U.S. National Institutes of Health. | |||||
| REF 3 | ClinicalTrials.gov (NCT02145741) Weekly Intravenous Administrations of BI 836845 in Japanese Patients With Advanced Solid Tumours. U.S. National Institutes of Health. | |||||
| REF 4 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7749). | |||||
| REF 5 | Clinical pipeline report, company report or official report of MedImmune (2011). | |||||
| REF 6 | Pharmacodynamic and antineoplastic activity of BI 836845, a fully human IGF ligand-neutralizing antibody, and mechanistic rationale for combination with rapamycin.Mol Cancer Ther.2014 Feb;13(2):399-409. | |||||
| REF 7 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | |||||
| REF 8 | Crystal structure of human insulin-like growth factor-1: detergent binding inhibits binding protein interactions. Biochemistry. 2001 Sep 18;40(37):11022-9. | |||||
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