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
Drug Property Profile of Target
Co-Targets
Target Poor or Non Binders
Target Profiles in Patients
Target Affiliated Biological Pathways
Target-Related Models and Studies
References
Drug Binding Sites of Target  Top
Ligand Name: MDL 101,146 Ligand Info
Structure Description CRYSTAL STRUCTURE OF HUMAN NEUTROPHIL ELASTASE WITH MDL 101, 146 PDB:1B0F
Method X-ray diffraction Resolution 3.00 Å Mutation No [65]
PDB Sequence
IVGGRRARPH
25
AWPFMVSLQL
35
AGGHFCGATL
46
IAPNFVMSAA
56
HCVANVNVRA
64

VRVVLGAHNL
73
SRREPTRQVF
83
AVQRIFEDGY
94
DPVNLLNDIV
104
ILQLNGSATI
114

NANVQVAQLP
124
AQGRRLGNGV
134
QCLAMGWGLL
144
GRNRGIASVL
155
QELNVTVVTS
166

LCRRSNVCTL
184
VRGRQAGVCF
192
GDSGSPLVCN
204
GLIHGIASFV
216
RGGCASGLYP
225

DAFAPVAQFV
235
NWIDSIIQ
Residue
Distance (Å)
PHE41
3.430
CYS42
3.034
HIS57
2.801
CYS58
3.715
LEU99B
3.728
ARG177
3.444
VAL190
4.251
CYS191
3.378
PHE192
3.251
Residue
Distance (Å)
GLY193
2.741
ASP194
2.953
SER195
1.488
ALA213
4.741
SER214
3.062
PHE215
3.142
VAL216
2.964
ARG217
3.498
Ligand Name: 1-(3-Chlorophenyl)-5-(3,5-Dimethylisoxazol-4-Yl)-6-Methyl-N-[4-(Methylsulfonyl)benzyl]-2-Oxo-1,2-Dihydropyridine-3-Carboxamide Ligand Info
Structure Description Neutrophil elastase inhibitors for the treatment of (cardio)pulmonary diseases PDB:5ABW
Method X-ray diffraction Resolution 1.60 Å Mutation No [66]
PDB Sequence
IVGGRRARPH
25
AWPFMVSLQL
35
RGGHFCGATL
46
IAPNFVMSAA
56
HCVANVNVRA
63C

VRVVLGAHNL
73
SRREPTRQVF
83
AVQRIFENGY
94
DPVNLLNDIV
104
ILQLNGSATI
114

NANVQVAQLP
124
AQGRRLGNGV
134
QCLAMGWGLL
144
GGIASVLQEL
158
NVTVVTSLCR
177

RSNVCTLVRG
186A
RQAGVCFGDS
195
GSPLVCNGLI
209
HGIASFVRGG
219
CASGLYPDAF
228

APVAQFVNWI
238
DSIIQ
Residue
Distance (Å)
HIS57
3.538
TYR94
4.314
ASN98
3.704
LEU99
3.735
ARG177
3.510
VAL190
4.278
CYS191
3.320
PHE192
3.330
Residue
Distance (Å)
ASP194
4.389
SER195
3.560
ALA213
3.564
SER214
3.292
PHE215
3.376
VAL216
2.879
ARG217
3.586
CYS220
4.427
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
There is no similarity protein (E value < 0.005) for this target
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
Neutrophil extracellular trap formation hsa04613 Affiliated Target
  Class: Organismal Systems => Immune system Pathway Hierarchy
Degree 5 Degree centrality 5.37E-04 Betweenness centrality 3.09E-05
Closeness centrality 1.79E-01 Radiality 1.29E+01 Clustering coefficient 0.00E+00
Neighborhood connectivity 4.80E+00 Topological coefficient 2.38E-01 Eccentricity 12
Download Click to Download the Full PPI Network of This Target

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