Target Information
Target General Information | Top | |||||
---|---|---|---|---|---|---|
Target ID |
T25315
(Former ID: TTDC00125)
|
|||||
Target Name |
C-X-C chemokine receptor type 3 (CXCR3)
|
|||||
Synonyms |
Interferon-inducible protein 10 receptor; IP-10 receptor; GPR9; G protein-coupled receptor 9; Chemokine receptor CXCR3/interferon-inducible protein-10; Chemokine receptor CXCR3; CXCR3/IP-10; CXCR-3; CXC-R3; CKR-L2; CD183 antigen; CD183
Click to Show/Hide
|
|||||
Gene Name |
CXCR3
|
|||||
Target Type |
Preclinical target
|
[1] | ||||
Disease | [+] 4 Target-related Diseases | + | ||||
1 | Psoriasis [ICD-11: EA90] | |||||
2 | Hepatic fibrosis/cirrhosis [ICD-11: DB93] | |||||
3 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
4 | Postoperative inflammation [ICD-11: 1A00-CA43] | |||||
Function |
Binds to CCL21. Probably promotes cell chemotaxis response. Isoform 1: Receptor for the C-X-C chemokine CXCL9, CXCL10 and CXCL11 and mediates the proliferation, survival and angiogenic activity of human mesangial cells (HMC) through a heterotrimeric G-protein signaling pathway.
Click to Show/Hide
|
|||||
BioChemical Class |
GPCR rhodopsin
|
|||||
UniProt ID | ||||||
Sequence |
MVLEVSDHQVLNDAEVAALLENFSSSYDYGENESDSCCTSPPCPQDFSLNFDRAFLPALY
SLLFLLGLLGNGAVAAVLLSRRTALSSTDTFLLHLAVADTLLVLTLPLWAVDAAVQWVFG SGLCKVAGALFNINFYAGALLLACISFDRYLNIVHATQLYRRGPPARVTLTCLAVWGLCL LFALPDFIFLSAHHDERLNATHCQYNFPQVGRTALRVLQLVAGFLLPLLVMAYCYAHILA VLLVSRGQRRLRAMRLVVVVVVAFALCWTPYHLVVLVDILMDLGALARNCGRESRVDVAK SVTSGLGYMHCCLNPLLYAFVGVKFRERMWMLLLRLGCPNQRGLQRQPSSSRRDSSWSET SEASYSGL Click to Show/Hide
|
|||||
3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
ADReCS ID | BADD_A06414 ; BADD_A08478 |
Drugs and Modes of Action | Top | |||||
---|---|---|---|---|---|---|
Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
1 | T487 | Drug Info | Discontinued in Phase 2 | Psoriatic disorder | [2] | |
Preclinical Drug(s) | [+] 2 Preclinical Drugs | + | ||||
1 | dioscin | Drug Info | Preclinical | Hepatic fibrosis | [3] | |
2 | JT07 | Drug Info | Preclinical | Solid tumour/cancer | [4] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Antagonist | [+] 6 Antagonist drugs | + | ||||
1 | T487 | Drug Info | [1], [5] | |||
2 | dioscin | Drug Info | [6] | |||
3 | hypoglaucin A | Drug Info | [6] | |||
4 | kallstroemin D | Drug Info | [6] | |||
5 | NBI-74330 | Drug Info | [1] | |||
6 | Sch-900875 | Drug Info | [7] | |||
Inhibitor | [+] 1 Inhibitor drugs | + | ||||
1 | JT07 | Drug Info | [4] |
Cell-based Target Expression Variations | Top | |||||
---|---|---|---|---|---|---|
Cell-based Target Expression Variations |
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 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 Pathway Affiliation
Biological Network Descriptors
|
There is no similarity protein (E value < 0.005) for this target
|
KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
---|---|---|---|
Cytokine-cytokine receptor interaction | hsa04060 | Affiliated Target |
|
Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
Viral protein interaction with cytokine and cytokine receptor | hsa04061 | Affiliated Target |
|
Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
Chemokine signaling pathway | hsa04062 | Affiliated Target |
|
Class: Organismal Systems => Immune system | Pathway Hierarchy |
Degree | 10 | Degree centrality | 1.07E-03 | Betweenness centrality | 3.15E-04 |
---|---|---|---|---|---|
Closeness centrality | 1.96E-01 | Radiality | 1.34E+01 | Clustering coefficient | 2.89E-01 |
Neighborhood connectivity | 9.80E+00 | Topological coefficient | 1.92E-01 | Eccentricity | 12 |
Download | Click to Download the Full PPI Network of This Target | ||||
Chemical Structure based Activity Landscape of Target | Top |
---|---|
Drug Property Profile of Target | Top | |
---|---|---|
(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
|
||
(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
|
||
(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
|
||
"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Target Poor or Non Binders | Top | |||||
---|---|---|---|---|---|---|
Target Poor or Non Binders |
Target Profiles in Patients | Top | |||||
---|---|---|---|---|---|---|
Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
---|---|---|---|---|---|---|
KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
1 | Cytokine-cytokine receptor interaction | |||||
2 | Chemokine signaling pathway | |||||
NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
1 | IL2 Signaling Pathway | |||||
Panther Pathway | [+] 1 Panther Pathways | + | ||||
1 | Inflammation mediated by chemokine and cytokine signaling pathway | |||||
PID Pathway | [+] 1 PID Pathways | + | ||||
1 | CXCR3-mediated signaling events | |||||
Reactome | [+] 2 Reactome Pathways | + | ||||
1 | Chemokine receptors bind chemokines | |||||
2 | G alpha (i) signalling events | |||||
WikiPathways | [+] 5 WikiPathways | + | ||||
1 | GPCRs, Class A Rhodopsin-like | |||||
2 | Peptide GPCRs | |||||
3 | GPCR ligand binding | |||||
4 | GPCR downstream signaling | |||||
5 | GPCRs, Other |
Target-Related Models and Studies | Top | |||||
---|---|---|---|---|---|---|
Target Validation | ||||||
Target QSAR Model |
References | Top | |||||
---|---|---|---|---|---|---|
REF 1 | Pharmacological characterization of CXC chemokine receptor 3 ligands and a small molecule antagonist. J Pharmacol Exp Ther. 2005 Jun;313(3):1263-71. | |||||
REF 2 | Clinical pipeline report, company report or official report of ChemoCentryx. | |||||
REF 3 | Drugs and Targets in Fibrosis. Front Pharmacol. 2017 Nov 23;8:855. | |||||
REF 4 | Clinical pipeline report, company report or official report of Jyant Technologies. | |||||
REF 5 | FANCG is phosphorylated at serines 383 and 387 during mitosis. Mol Cell Biol. 2004 Oct;24(19):8576-85. | |||||
REF 6 | Discovery of structurally diverse natural product antagonists of chemokine receptor CXCR3. Mol Divers. 2005;9(1-3):123-9. | |||||
REF 7 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 70). |
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.