Target Information
Target General Information | Top | |||||
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Target ID |
T44141
(Former ID: TTDC00247)
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Target Name |
Angiopoietin-1 (ANGPT1)
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Synonyms |
Angiopoietin1; ANGPT1; ANG1; ANG-1
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Gene Name |
ANGPT1
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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 | General pain disorder [ICD-11: 8E43] | |||||
3 | Ovarian cancer [ICD-11: 2C73] | |||||
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.
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BioChemical Class |
Fibrinogen protein
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UniProt ID | ||||||
Sequence |
MTVFLSFAFLAAILTHIGCSNQRRSPENSGRRYNRIQHGQCAYTFILPEHDGNCRESTTD
QYNTNALQRDAPHVEPDFSSQKLQHLEHVMENYTQWLQKLENYIVENMKSEMAQIQQNAV QNHTATMLEIGTSLLSQTAEQTRKLTDVETQVLNQTSRLEIQLLENSLSTYKLEKQLLQQ TNEILKIHEKNSLLEHKILEMEGKHKEELDTLKEEKENLQGLVTRQTYIIQELEKQLNRA TTNNSVLQKQQLELMDTVHNLVNLCTKEGVLLKGGKREEEKPFRDCADVYQAGFNKSGIY TIYINNMPEPKKVFCNMDVNGGGWTVIQHREDGSLDFQRGWKEYKMGFGNPSGEYWLGNE FIFAITSQRQYMLRIELMDWEGNRAYSQYDRFHIGNEKQNYRLYLKGHTGTAGKQSSLIL HGADFSTKDADNDNCMCKCALMLTGGWWFDACGPSNLNGMFYTAGQNHGKLNGIKWHYFK GPSYSLRSTTMMIRPLDF Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T54D6L |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
1 | AMG 386 | Drug Info | Phase 3 | Neuropathic pain | [2] | |
2 | Trebananib | Drug Info | Phase 3 | Ovarian cancer | [3] | |
3 | AMG 780 | Drug Info | Phase 1 | Solid tumour/cancer | [4] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Modulator | [+] 2 Modulator drugs | + | ||||
1 | AMG 386 | Drug Info | [1] | |||
2 | AMG 780 | Drug Info | [6] | |||
Inhibitor | [+] 1 Inhibitor drugs | + | ||||
1 | Trebananib | Drug Info | [5] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
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 Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
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 Tissue Distribution
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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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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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 | ||
PI3K-Akt signaling pathway | hsa04151 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy |
Degree | 6 | Degree centrality | 6.45E-04 | Betweenness centrality | 1.53E-05 |
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Closeness centrality | 2.18E-01 | Radiality | 1.38E+01 | Clustering coefficient | 4.00E-01 |
Neighborhood connectivity | 3.70E+01 | Topological coefficient | 2.28E-01 | Eccentricity | 12 |
Download | Click to Download the Full PPI Network of This Target | ||||
Target Regulators | Top | |||||
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Target-interacting Proteins |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 5 KEGG Pathways | + | ||||
1 | Ras signaling pathway | |||||
2 | Rap1 signaling pathway | |||||
3 | HIF-1 signaling pathway | |||||
4 | PI3K-Akt signaling pathway | |||||
5 | Rheumatoid arthritis | |||||
NetPath Pathway | [+] 3 NetPath Pathways | + | ||||
1 | TGF_beta_Receptor Signaling Pathway | |||||
2 | TNFalpha Signaling Pathway | |||||
3 | FSH Signaling Pathway | |||||
Panther Pathway | [+] 1 Panther Pathways | + | ||||
1 | Angiogenesis | |||||
PID Pathway | [+] 2 PID Pathways | + | ||||
1 | Angiopoietin receptor Tie2-mediated signaling | |||||
2 | SHP2 signaling | |||||
Reactome | [+] 2 Reactome Pathways | + | ||||
1 | Tie2 Signaling | |||||
2 | RAF/MAP kinase cascade | |||||
WikiPathways | [+] 2 WikiPathways | + | ||||
1 | Cell surface interactions at the vascular wall | |||||
2 | Angiogenesis |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | |||||
REF 2 | Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26. | |||||
REF 3 | ClinicalTrials.gov (NCT01281254) AMG 386 (Trebananib) in Ovarian Cancer (TRINOVA-2). U.S. National Institutes of Health. | |||||
REF 4 | Development 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 5 | Pediatric Phase I Trial and Pharmacokinetic Study of Trebananib in Relapsed Solid Tumors, Including Primary Tumors of the Central Nervous System ADVL1115: A Children's Oncology Group Phase I Consortium Report. Clin Cancer Res. 2017 Oct 15;23(20):6062-6069. | |||||
REF 6 | Development 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. |
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