Target General Infomation
Target ID
T44141
Former ID
TTDC00247
Target Name
Angiopoietin-1
Gene Name
ANGPT1
Synonyms
ANG-1; ANG1; Angiopoietin1; ANGPT1
Target Type
Clinical Trial
Disease Breast cancer [ICD9: 174, 175; ICD10: C50]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Function
Binds and activates TEK/TIE2 receptor by inducing its dimerization and tyrosine phosphorylation. Plays an important role in the regulation of angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Required for normal angiogenesis and heart development during embryogenesis. After birth, activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. Mediates blood vessel maturation/stability. Implicated in endothelial developmental processes laterand distinct from that of VEGF. Appears to play a crucial role in mediating reciprocal interactions between the endothelium and surrounding matrix and mesenchyme.
BioChemical Class
Fibrinogen
Target Validation
T44141
UniProt ID
Sequence
MTVFLSFAFLAAILTHIGCSNQRRSPENSGRRYNRIQHGQCAYTFILPEHDGNCRESTTD
QYNTNALQRDAPHVEPDFSSQKLQHLEHVMENYTQWLQKLENYIVENMKSEMAQIQQNAV
QNHTATMLEIGTSLLSQTAEQTRKLTDVETQVLNQTSRLEIQLLENSLSTYKLEKQLLQQ
TNEILKIHEKNSLLEHKILEMEGKHKEELDTLKEEKENLQGLVTRQTYIIQELEKQLNRA
TTNNSVLQKQQLELMDTVHNLVNLCTKEGVLLKGGKREEEKPFRDCADVYQAGFNKSGIY
TIYINNMPEPKKVFCNMDVNGGGWTVIQHREDGSLDFQRGWKEYKMGFGNPSGEYWLGNE
FIFAITSQRQYMLRIELMDWEGNRAYSQYDRFHIGNEKQNYRLYLKGHTGTAGKQSSLIL
HGADFSTKDADNDNCMCKCALMLTGGWWFDACGPSNLNGMFYTAGQNHGKLNGIKWHYFK
GPSYSLRSTTMMIRPLDF
Structure
4EPU; 4JYO; 4K0V
Drugs and Mode of Action
Drug(s) AMG 386 Drug Info Phase 3 Breast cancer [523327], [543118]
AMG 780 Drug Info Phase 1 Cancer [549765]
Modulator AMG 386 Drug Info [1572591]
AMG 780 Drug Info [549766]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Ras signaling pathway
Rap1 signaling pathway
HIF-1 signaling pathway
PI3K-Akt signaling pathway
Rheumatoid arthritis
NetPath Pathway TGF_beta_Receptor Signaling Pathway
TNFalpha Signaling Pathway
FSH Signaling Pathway
PANTHER Pathway Angiogenesis
Pathway Interaction Database Angiopoietin receptor Tie2-mediated signaling
SHP2 signaling
Reactome Tie2 Signaling
RAF/MAP kinase cascade
WikiPathways Cell surface interactions at the vascular wall
Angiogenesis
References
Ref 523327ClinicalTrials.gov (NCT01281254) TRINOVA-2: Trebananib in Ovarian Cancer-2. U.S. National Institutes of Health.
Ref 543118(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: 8414).
Ref 549765Development and preclinical testing of AMG 780, a fully human antibody targeting angiopoietin 1 (Ang1) and angiopoietin 2 (Ang2). Cancer Research. 10/2014; 74(19 Supplement):1022-1022.
Ref
Ref 549766Development and preclinical testing of AMG 780, a fully human antibody targeting angiopoietin 1 (Ang1) and angiopoietin 2 (Ang2). Cancer Research. 10/2014; 74(19 Supplement):1022-1022.
Ref 1572591Interpreting 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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