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] |
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. |
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