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 Regulators
Target Profiles in Patients
Target Affiliated Biological Pathways
Target-Related Models and Studies
References
Drug Binding Sites of Target  Top
Ligand Name: Acetazolamide Ligand Info
Structure Description Crystal structure of the catalytic domain of the tumor-associated human carbonic anhydrase IX PDB:3IAI
Method X-ray diffraction Resolution 2.20 Å Mutation Yes [51]
PDB Sequence
GPDQSHWRYG
8
GDPPWPRVSP
21
ACAGRFQSPV
31
DIRPQLAAFS
41
PALRPLELLG
50A

FQLPPLPELR
58
LRNNGHSVQL
68
TLPPGLEMAL
81
GPGREYRALQ
92
LHLHWGAAGR
102

PGSEHTVEGH
112
RFPAEIHVVH
122
LSTAFARVDE
133
ALGRPGGLAV
143
LAAFLEEGPE
152

ENSAYEQLLS
162
RLEEIAEEGS
172
ETQVPGLDIS
182
ALLPSDFSRY
191
FQYEGSLTTP
201

PCAQGVIWTV
211
FNQTVMLSAK
221
QLHTLSDTLW
230
GPGDSRLQLN
244
FRATQPLNGR
254

VIEASFP
Residue
Distance (Å)
GLN92
3.249
HIS94
3.080
HIS96
3.360
GLU106
3.858
HIS119
3.469
VAL121
3.634
VAL131
3.910
Residue
Distance (Å)
VAL143
4.220
SER197
4.560
LEU198
3.436
THR199
2.754
THR200
2.843
PRO201
4.618
TRP209
3.422
Ligand Name: 4-[2-[3-(Cyclooctylamino)-2,5,6-tris(fluoranyl)-4-sulfamoyl-phenyl]sulfanylethyl]benzoic acid Ligand Info
Structure Description Three dimensional structure of human carbonic anhydrase IX in complex with sulfonamide PDB:6G9U
Method X-ray diffraction Resolution 1.75 Å Mutation Yes [52]
PDB Sequence
RVSPACAGRF
27
QSPVDIRPQL
37
AAFSPALRPL
47
ELLGFQLPPL
54B
PELRLRNNGH
64

SVQLTLPPGL
77
EMALGPGREY
88
RALQLHLHWG
98
AAGRPGSEHT
108
VEGHRFPAEI
118

HVVHLSTAFA
129
RVDEALGRPG
139
GLAVLAAFLE
149
EGPEENSAYE
158
QLLSRLEEIA
168

EEGSETQVPG
178
LDISALLPSD
188
FSRYFQYEGS
197
LTTPPCAQGV
207
IWTVFNQTVM
217

LSAKQLHTLS
227
DTLWGPGDSR
240
LQLNFRATQP
250
LNGRVIEASF
260
P
Residue
Distance (Å)
ARG60
3.278
ASN62
3.443
HIS64
3.640
SER65
4.046
GLN67
3.283
LEU91
4.597
GLN92
3.130
HIS94
3.203
HIS96
3.266
GLU106
3.780
Residue
Distance (Å)
HIS119
3.334
VAL121
3.783
VAL131
4.030
LEU135
4.823
LEU141
4.358
VAL143
4.712
LEU198
3.498
THR199
2.781
THR200
3.458
TRP209
4.088
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
Nitrogen metabolism hsa00910 Affiliated Target
  Class: Metabolism => Energy metabolism Pathway Hierarchy
Degree 5 Degree centrality 5.37E-04 Betweenness centrality 3.85E-04
Closeness centrality 2.18E-01 Radiality 1.38E+01 Clustering coefficient 4.00E-01
Neighborhood connectivity 2.22E+01 Topological coefficient 2.68E-01 Eccentricity 11
Download Click to Download the Full PPI Network of This Target

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