Target Information
Target General Information | Top | |||||
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Target ID |
T92963
(Former ID: TTDI01819)
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Target Name |
Natriuretic peptide receptor (NPR3)
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Synonyms |
NPR3
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Gene Name |
NPR3
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Heart failure [ICD-11: BD10-BD1Z] | |||||
Function |
Receptor for the atrial natriuretic peptide NPPA/ANP and the brain natriuretic peptide NPPB/BNP which are potent vasoactive hormones playing a key role in cardiovascular homeostasis. Has guanylate cyclase activity upon binding of the ligand.
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BioChemical Class |
Phosphorus-oxygen lyase
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UniProt ID | ||||||
Sequence |
MPSLLVLTFSPCVLLGWALLAGGTGGGGVGGGGGGAGIGGGRQEREALPPQKIEVLVLLP
QDDSYLFSLTRVRPAIEYALRSVEGNGTGRRLLPPGTRFQVAYEDSDCGNRALFSLVDRV AAARGAKPDLILGPVCEYAAAPVARLASHWDLPMLSAGALAAGFQHKDSEYSHLTRVAPA YAKMGEMMLALFRHHHWSRAALVYSDDKLERNCYFTLEGVHEVFQEEGLHTSIYSFDETK DLDLEDIVRNIQASERVVIMCASSDTIRSIMLVAHRHGMTSGDYAFFNIELFNSSSYGDG SWKRGDKHDFEAKQAYSSLQTVTLLRTVKPEFEKFSMEVKSSVEKQGLNMEDYVNMFVEG FHDAILLYVLALHEVLRAGYSKKDGGKIIQQTWNRTFEGIAGQVSIDANGDRYGDFSVIA MTDVEAGTQEVIGDYFGKEGRFEMRPNVKYPWGPLKLRIDENRIVEHTNSSPCKSSGGLE ESAVTGIVVGALLGAGLLMAFYFFRKKYRITIERRTQQEESNLGKHRELREDSIRSHFSV A Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
HIT2.0 ID | T41S16 |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | ANX-042 | Drug Info | Phase 1 | Chronic heart failure | [2] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | ANX-042 | Drug Info | [1] | |||
Antagonist | [+] 2 Antagonist drugs | + | ||||
1 | AP811 | Drug Info | [3] | |||
2 | M372049 | Drug Info | [4] |
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).
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
Biological Network Descriptors
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Protein Name | Pfam ID | Percentage of Identity (%) | E value |
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Guanylyl cyclase C (GUCY2C) | 22.287 (76/341) | 1.91E-04 |
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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Degree | 4 | Degree centrality | 4.30E-04 | Betweenness centrality | 7.42E-04 |
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Closeness centrality | 1.61E-01 | Radiality | 1.24E+01 | Clustering coefficient | 0.00E+00 |
Neighborhood connectivity | 4.00E+00 | Topological coefficient | 3.75E-01 | Eccentricity | 13 |
Download | Click to Download the Full PPI Network of This Target | ||||
Chemical Structure based Activity Landscape of Target | Top |
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References | Top | |||||
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REF 1 | Renin-Angiotensin Blockade Combined With Natriuretic Peptide System Augmentation: Novel Therapeutic Concepts to Combat Heart Failure. Circ Heart Fail. 2013 May; 6(3): 594-605. | |||||
REF 2 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800036485) | |||||
REF 3 | The discovery of non-basic atrial natriuretic peptide clearance receptor antagonists. Part 1. Bioorg Med Chem Lett. 2000 Sep 4;10(17):1949-52. | |||||
REF 4 | Natriuretic peptide receptor-C regulates coronary blood flow and prevents myocardial ischemia/reperfusion injury: novel cardioprotective role for e... Circulation. 2004 Sep 7;110(10):1231-5. |
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