Target Information

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Target General Information
Drugs and Modes of Action
Drug Binding Sites of Target
Different Human System Profiles of Target
Chemical Structure based Activity Landscape of Target
Target Poor or Non Binders
Target Regulators
Target Affiliated Biological Pathways
References
Drug Binding Sites of Target  Top
Ligand Name: 7-methoxy-~{N}-[(3~{S})-1-(4-methylphenyl)pyrrolidin-3-yl]-1~{H}-indole-3-carboxamide Ligand Info
Structure Description HDMX (14-111; C17S) COMPLEXED WITH COMPOUND 16 AT 1.20A; Structural states of Hdm2 and HdmX: X-ray elucidation of adaptations and binding interactions for different chemical compound classes PDB:6Q9Y
Method X-ray diffraction Resolution 1.20 Å Mutation Yes [4]
PDB Sequence
QVRPKLPLLK
36
ILHAAGAQGE
46
MFTVKEVMHY
56
LGQYIMVKQL
66
YDQQEQHMVY
76

CGGDLLGELL
86
GRQSFSVKDP
96
SPLYDMLRKN
106
LVTLA
Residue
Distance (Å)
MET54
3.838
LEU57
3.851
GLY58
3.463
ILE61
3.496
MET62
3.919
TYR67
3.357
GLN72
2.791
HIS73
4.279
Residue
Distance (Å)
MET74
4.859
VAL75
3.451
PHE91
3.346
VAL93
3.310
PRO96
3.704
LEU99
3.536
TYR100
3.851
LEU103
3.766
Ligand Name: (4~{S})-4-(4-chlorophenyl)-5-[(1~{S})-1-(3-chlorophenyl)ethyl]-2-(2,4-dimethoxypyrimidin-5-yl)-3-propan-2-yl-4~{H}-pyrrolo[3,4-d]imidazol-6-one Ligand Info
Structure Description X-ray structure of compound 15 bound to HdmX: Structural states of Hdm2 and HdmX: X-ray elucidation of adaptations and binding interactions for different chemical compound classes PDB:6Q9W
Method X-ray diffraction Resolution 1.55 Å Mutation Yes [4]
PDB Sequence
NQVRPKLPLL
35
KILHAAGAQG
45
EMFTVKEVMH
55
YLGQYIMVKQ
65
LYDQQEQHMV
75

YCGGDLLGEL
85
LGRQSFSVKD
95
PSPLYDMLRK
105
NLVTLA
Residue
Distance (Å)
MET54
3.540
LEU57
3.707
GLY58
3.497
GLN59
4.826
ILE61
3.450
MET62
3.692
TYR67
3.186
ASP68
4.115
GLN69
3.655
GLN72
3.216
Residue
Distance (Å)
HIS73
3.718
MET74
3.133
VAL75
3.864
PHE91
3.932
SER92
4.621
VAL93
3.791
PRO96
3.478
LEU99
3.534
TYR100
3.089
Click to View More Binding Site Information of This Target with Different Ligands
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
Peroxisome assembly protein 12 (PEX12)
PF04757
24.528 (39/159) 1.00E-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.
 Download Picture         KEGG Link      
KEGG Pathway Pathway ID Affiliated Target Pathway Map
p53 signaling pathway hsa04115 Affiliated Target
  Class: Cellular Processes => Cell growth and death Pathway Hierarchy
Degree 12 Degree centrality 1.29E-03 Betweenness centrality 9.88E-05
Closeness centrality 2.44E-01 Radiality 1.43E+01 Clustering coefficient 3.64E-01
Neighborhood connectivity 7.07E+01 Topological coefficient 1.26E-01 Eccentricity 12
Download Click to Download the Full PPI Network of This Target

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