Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTT6LOU)

• DTT Name: Insulin-like growth factor-I (IGF1)
• Synonyms: SomatomedinC; Somatomedin-C; Mechano growth factor; Insulin-like growth factor I; IGFI; IGF-I
• Gene Name: IGF1
• DTT Type: Clinical trial target; [1]
• UniProt ID: IGF1_HUMAN
• TTD ID: T60930
• Sequence:
  MGKISSLPTQLFKCCFCDFLKVKMHTMSSSHLFYLALCLLTFTSSATAGPETLCGAELVD
  ALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSARS
  VRAQRHTDMPKTQKYQPPSTNKNTKSQRRKGWPKTHPGGEQKEGTEASLQIRGKKKEQRR
  EIGSRNAECRGKKGK
• 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.
• KEGG Pathway:
  EGFR tyrosine kinase inhibitor resistance (hsa01521)
  Endocrine resistance (hsa01522)
  MAPK signaling pathway (hsa04010)
  Ras signaling pathway (hsa04014)
  Rap1 signaling pathway (hsa04015)
  HIF-1 signaling pathway (hsa04066)
  FoxO signaling pathway (hsa04068)
  Oocyte meiosis (hsa04114)
  p53 signaling pathway (hsa04115)
  mTOR signaling pathway (hsa04150)
  PI3K-Akt signaling pathway (hsa04151)
  AMPK signaling pathway (hsa04152)
  Longevity regulating pathway (hsa04211)
  Longevity regulating pathway - multiple species (hsa04213)
  Focal adhesion (hsa04510)
  Signaling pathways regulating pluripotency of stem cells (hsa04550)
  Long-term depression (hsa04730)
  Inflammatory mediator regulation of TRP channels (hsa04750)
  Ovarian steroidogenesis (hsa04913)
  Progesterone-mediated oocyte maturation (hsa04914)
  Growth hormone synthesis, secretion and action (hsa04935)
  Aldosterone-regulated sodium reabsorption (hsa04960)
  Pathways in cancer (hsa05200)
  Transcriptional misregulation in cancer (hsa05202)
  Proteoglycans in cancer (hsa05205)
  Glioma (hsa05214)
  Prostate cancer (hsa05215)
  Melanoma (hsa05218)
  Breast cancer (hsa05224)
  Hypertrophic cardiomyopathy (hsa05410)
  Dilated cardiomyopathy (hsa05414)
• Reactome Pathway:
  Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) (R-HSA-2404192)
  IRS-related events triggered by IGF1R (R-HSA-2428928)
  SHC-related events triggered by IGF1R (R-HSA-2428933)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  Synthesis, secretion, and deacylation of Ghrelin (R-HSA-422085)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DTT

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Xentuzumab	DM4ZIDH	Breast cancer	2C60-2C65	Phase 2	[1]
BI-836845	DM4T916	Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]
MEDI-573	DMNL8MO	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] 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.
• [3] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.