Target Information

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Target General Information
Drugs and Modes of Action
Different Human System Profiles of Target
Chemical Structure based Activity Landscape of Target
Drug Property Profile of Target
Target Profiles in Patients
Target Affiliated Biological Pathways
Target-Related Models and Studies
References
Different Human System Profiles of Target  Top
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
Protein Name Pfam ID Percentage of Identity (%) E value
Calpain small subunit 1 (CAPNS1) 43.069 (87/202) 1.33E-52
Peflin (PEF1)
PF13405 ; 
PF13499
29.508 (36/122) 3.52E-16
Programmed cell death protein 6 (PDCD6)
PF13202 ; 
PF13499
26.400 (33/125) 1.96E-12
Calmodulin-like protein 5 (CALML5)
PF13499
23.853 (26/109) 2.00E-03
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
Protein processing in endoplasmic reticulum hsa04141 Affiliated Target
  Class: Genetic Information Processing => Folding, sorting and degradation Pathway Hierarchy
Apoptosis hsa04210 Affiliated Target
  Class: Cellular Processes => Cell growth and death Pathway Hierarchy
Necroptosis hsa04217 Affiliated Target
  Class: Cellular Processes => Cell growth and death Pathway Hierarchy
Cellular senescence hsa04218 Affiliated Target
  Class: Cellular Processes => Cell growth and death Pathway Hierarchy
Focal adhesion hsa04510 Affiliated Target
  Class: Cellular Processes => Cellular community - eukaryotes Pathway Hierarchy
Degree 5 Degree centrality 5.37E-04 Betweenness centrality 3.33E-04
Closeness centrality 2.18E-01 Radiality 1.38E+01 Clustering coefficient 2.00E-01
Neighborhood connectivity 3.38E+01 Topological coefficient 2.40E-01 Eccentricity 12
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