Target Information
| Target General Information | Top | |||||
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| Target ID |
T70792
(Former ID: TTDNS00541)
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| Target Name |
Placenta growth factor (PlGF)
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| Synonyms |
SHGC-10760; PlGF-2; PLGF; PGFL; D12S1900
Click to Show/Hide
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| Gene Name |
PGF
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Colorectal cancer [ICD-11: 2B91] | |||||
| Function |
It binds to the receptor FLT1/VEGFR-1. Isoform PlGF-2 binds NRP1/neuropilin-1 and NRP2/neuropilin-2 in a heparin-dependent manner. Also promotes cell tumor growth. Growth factor active in angiogenesis and endothelial cell growth, stimulating their proliferation and migration.
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| BioChemical Class |
Growth factor
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| UniProt ID | ||||||
| Sequence |
MPVMRLFPCFLQLLAGLALPAVPPQQWALSAGNGSSEVEVVPFQEVWGRSYCRALERLVD
VVSEYPSEVEHMFSPSCVSLLRCTGCCGDENLHCVPVETANVTMQLLKIRSGDRPSYVEL TFSQHVRCECRHSPGRQSPDMPGDFRADAPSFLPPRRSLPMLFRMEWGCALTGSQSAVWP SSPVPEEIPRMHPGRNGKKQQRKPLREKMKPERCGDAVPRR Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T84XW5 | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Aflibercept | Drug Info | Approved | Metastatic colorectal cancer | [1] | |
| Clinical Trial Drug(s) | [+] 4 Clinical Trial Drugs | + | ||||
| 1 | RO-5323441 | Drug Info | Phase 2 | Solid tumour/cancer | [2] | |
| 2 | TB-403 | Drug Info | Phase 2 | Glioblastoma of brain | [2] | |
| 3 | R7334 | Drug Info | Phase 1 | Macular degeneration | [3] | |
| 4 | SFLT-01 | Drug Info | Phase 1 | Macular degeneration | [4] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | Aflibercept | Drug Info | [1] | |||
| 2 | SFLT-01 | Drug Info | [8] | |||
| Inhibitor | [+] 3 Inhibitor drugs | + | ||||
| 1 | RO-5323441 | Drug Info | [5] | |||
| 2 | TB-403 | Drug Info | [6] | |||
| 3 | 2-Methyl-2,4-Pentanediol | Drug Info | [9] | |||
| 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 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 |
|---|---|---|---|
| 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 | ||
| PI3K-Akt signaling pathway | hsa04151 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Focal adhesion | hsa04510 | Affiliated Target |
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| Class: Cellular Processes => Cellular community - eukaryotes | Pathway Hierarchy | ||
| Degree | 5 | Degree centrality | 5.37E-04 | Betweenness centrality | 7.04E-06 |
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| Closeness centrality | 2.14E-01 | Radiality | 1.38E+01 | Clustering coefficient | 7.00E-01 |
| Neighborhood connectivity | 3.54E+01 | Topological coefficient | 3.00E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| 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 | [+] 7 KEGG Pathways | + | ||||
| 1 | Ras signaling pathway | |||||
| 2 | Rap1 signaling pathway | |||||
| 3 | PI3K-Akt signaling pathway | |||||
| 4 | Focal adhesion | |||||
| 5 | Pathways in cancer | |||||
| 6 | Glycosylphosphatidylinositol(GPI)-anchor biosynthesis | |||||
| 7 | Metabolic pathways | |||||
| NetPath Pathway | [+] 2 NetPath Pathways | + | ||||
| 1 | TSH Signaling Pathway | |||||
| 2 | TCR Signaling Pathway | |||||
| PID Pathway | [+] 1 PID Pathways | + | ||||
| 1 | VEGFR1 specific signals | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | VEGF ligand-receptor interactions | |||||
| 2 | VEGF binds to VEGFR leading to receptor dimerization | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | Focal Adhesion | |||||
| 2 | Signaling by VEGF | |||||
| 3 | Diurnally Regulated Genes with Circadian Orthologs | |||||
| 4 | Post-translational modification: synthesis of GPI-anchored proteins | |||||
| References | Top | |||||
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| REF 1 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 2 | ClinicalTrials.gov (NCT01622764) 89Zr-RO5323441 PET Imaging in Glioblastoma. U.S. National Institutes of Health. | |||||
| REF 3 | ClinicalTrials.gov (NCT00702494) Phase I Study on Monoclonal Antibody TB-403 Directed Against PlGF in Patients With Solid Tumours. U.S. National Institutes of Health. | |||||
| REF 4 | ClinicalTrials.gov (NCT01024998) Safety and Tolerability Study of AAV2-sFLT01 in Patients With Neovascular Age-Related Macular Degeneration (AMD). U.S. National Institutes of Health. | |||||
| REF 5 | RO5323441, a humanized monoclonal antibody against the placenta growth factor, blocks PlGF-induced VEGFR-1 phosphorylation in vitro and tumor growth in vivo. Cancer Research. 01/2011. | |||||
| REF 6 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 7 | Clinical pipeline report, company report or official report of Roche (2009). | |||||
| REF 8 | sFLT01: a novel fusion protein with antiangiogenic activity. Mol Cancer Ther. 2011 Mar;10(3):404-15. | |||||
| REF 9 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
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