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: Norleucine Ligand Info
Structure Description Human Mcl-1 in complex with a modified unnatural Bim BH3 peptide PDB:6UAB
Method X-ray diffraction Resolution 2.10 Å Mutation No [18]
PDB Sequence
SDELYRQSLE
180
IISRYLREQA
190
TGAKDTKPMG
200
RSGATSRKAL
210
ETLRRVGDGV
220

QRNHETAFQG
230
MLRKLDIKNE
240
DDVKSLSRVM
250
IHVFSDGVTN
260
WGRIVTLISF
270

GAFVAKHLKT
280
INQESCIEPL
290
AESITDVLVR
300
TKRDWLVKQR
310
GWDGFVEFFH
320

VEDLE
Residue
Distance (Å)
MET231
4.037
LYS234
3.434
Residue
Distance (Å)
LEU235
3.290
VAL249
4.349
Ligand Name: AZD5991 Ligand Info
Structure Description INDUCED MYELOID LEUKEMIA CELL DIFFERENTIATION PROTEIN FABCOMPLEX IN COMPLEX WITH AZD5991 PDB:6FS0
Method X-ray diffraction Resolution 2.25 Å Mutation No [19]
PDB Sequence
GPLGSEDDLY
175
RQSLEIISRY
185
LREQATGSKD
195
SKPLGEAGAA
205
GRRALETLRR
215

VGDGVQRNHE
225
TAFQGMLRKL
235
DIKNEDDVKS
245
LSRVMIHVFS
255
DGVTNWGRIV
265

TLISFGAFVA
275
KHLKTINQES
285
CIEPLAESIT
295
DVLVRTKRDW
305
LVKQRGWDGF
315

VEFFHV
Residue
Distance (Å)
HIS224
4.032
ALA227
3.462
PHE228
3.559
MET231
3.453
LEU235
3.792
LEU246
4.171
VAL249
3.549
MET250
3.871
VAL253
3.283
Residue
Distance (Å)
PHE254
3.868
ARG263
2.807
THR266
3.598
LEU267
3.246
PHE270
3.485
GLY271
3.681
VAL274
4.504
LEU290
3.984
ILE294
3.791
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.
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KEGG Pathway Pathway ID Affiliated Target Pathway Map
PI3K-Akt signaling pathway hsa04151 Affiliated Target
  Class: Environmental Information Processing => Signal transduction Pathway Hierarchy
Apoptosis hsa04210 Affiliated Target
  Class: Cellular Processes => Cell growth and death Pathway Hierarchy
JAK-STAT signaling pathway hsa04630 Affiliated Target
  Class: Environmental Information Processing => Signal transduction Pathway Hierarchy
Degree 25 Degree centrality 2.69E-03 Betweenness centrality 1.20E-03
Closeness centrality 2.56E-01 Radiality 1.44E+01 Clustering coefficient 1.70E-01
Neighborhood connectivity 4.34E+01 Topological coefficient 6.01E-02 Eccentricity 11
Download Click to Download the Full PPI Network of This Target

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