Target Information
Target General Information | Top | |||||
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Target ID |
T30635
(Former ID: TTDR00498)
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Target Name |
C-X-C motif chemokine 10 (CXCL10)
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Synonyms |
Small-inducible cytokine B10; SCYB10; IP-10; INP10; Gamma-IP10; 10 kDa interferon gamma-induced protein
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Gene Name |
CXCL10
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 6 Target-related Diseases | + | ||||
1 | Crohn disease [ICD-11: DD70] | |||||
2 | Diabetes mellitus [ICD-11: 5A10] | |||||
3 | Immune system disease [ICD-11: 4A01-4B41] | |||||
4 | Indeterminate colitis [ICD-11: DD72] | |||||
5 | Ulcerative colitis [ICD-11: DD71] | |||||
6 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
Function |
Pro-inflammatory cytokine that is involved in a wide variety of processes such as chemotaxis, differentiation, and activation of peripheral immune cells, regulation of cell growth, apoptosis and modulation of angiostatic effects. Plays thereby an important role during viral infections by stimulating the activation and migration of immune cells to the infected sites (By similarity). Mechanistically, binding of CXCL10 to the CXCR3 receptor activates G protein-mediated signaling and results in downstream activation of phospholipase C-dependent pathway, an increase in intracellular calcium production and actin reorganization. In turn, recruitment of activated Th1 lymphocytes occurs at sites of inflammation. Activation of the CXCL10/CXCR3 axis plays also an important role in neurons in response to brain injury for activating microglia, the resident macrophage population of the central nervous system, and directing them to the lesion site. This recruitment is an essential element for neuronal reorganization (By similarity).
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BioChemical Class |
Cytokine: CXC chemokine
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UniProt ID | ||||||
Sequence |
MNQTAILICCLIFLTLSGIQGVPLSRTVRCTCISISNQPVNPRSLEKLEIIPASQFCPRV
EIIATMKKKGEKRCLNPESKAIKNLLKAVSKERSKRSP Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
ADReCS ID | BADD_A05204 | |||||
HIT2.0 ID | T79UQC |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 4 Clinical Trial Drugs | + | ||||
1 | Anti-IP10 | Drug Info | Phase 2 | Ulcerative colitis | [3] | |
2 | BMS-936557 | Drug Info | Phase 2 | Immune System disease | [3] | |
3 | MDX-1100 | Drug Info | Phase 2 | Crohn disease | [4] | |
4 | NI-0801 | Drug Info | Phase 2 | Autoimmune diabetes | [5] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 1 Inhibitor drugs | + | ||||
1 | N-Methylleucine | Drug Info | [8] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Different Human System Profiles of Target | Top |
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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
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There is no similarity protein (E value < 0.005) for this target
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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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Cytokine-cytokine receptor interaction | hsa04060 | Affiliated Target |
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Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
Viral protein interaction with cytokine and cytokine receptor | hsa04061 | Affiliated Target |
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Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
Chemokine signaling pathway | hsa04062 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
Toll-like receptor signaling pathway | hsa04620 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
RIG-I-like receptor signaling pathway | hsa04622 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
Cytosolic DNA-sensing pathway | hsa04623 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
IL-17 signaling pathway | hsa04657 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
TNF signaling pathway | hsa04668 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
Click to Show/Hide the Information of Affiliated Human Pathways |
Degree | 24 | Degree centrality | 2.58E-03 | Betweenness centrality | 5.72E-04 |
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Closeness centrality | 2.20E-01 | Radiality | 1.39E+01 | Clustering coefficient | 4.02E-01 |
Neighborhood connectivity | 2.55E+01 | Topological coefficient | 1.13E-01 | Eccentricity | 11 |
Download | Click to Download the Full PPI Network of This Target | ||||
Target Regulators | Top | |||||
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Target-regulating microRNAs |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 7 KEGG Pathways | + | ||||
1 | Cytokine-cytokine receptor interaction | |||||
2 | Chemokine signaling pathway | |||||
3 | Toll-like receptor signaling pathway | |||||
4 | RIG-I-like receptor signaling pathway | |||||
5 | Cytosolic DNA-sensing pathway | |||||
6 | TNF signaling pathway | |||||
7 | Influenza A | |||||
NetPath Pathway | [+] 5 NetPath Pathways | + | ||||
1 | IL-7 Signaling Pathway | |||||
2 | TSLP Signaling Pathway | |||||
3 | TNFalpha Signaling Pathway | |||||
4 | TWEAK Signaling Pathway | |||||
5 | TCR 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 | [+] 6 WikiPathways | + | ||||
1 | Toll-like receptor signaling pathway | |||||
2 | Type II interferon signaling (IFNG) | |||||
3 | Spinal Cord Injury | |||||
4 | GPCR ligand binding | |||||
5 | GPCR downstream signaling | |||||
6 | Regulation of toll-like receptor signaling pathway |
References | Top | |||||
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REF 1 | Anti-IP-10 antibody (BMS-936557) for ulcerative colitis: a phase II randomised study. Gut. 2014 Mar;63(3):442-50. | |||||
REF 2 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
REF 3 | ClinicalTrials.gov (NCT01466374) Induction and Maintenance Study of BMS-936557 in Patients With Moderate to Severely Active Crohn's Disease. U.S. National Institutes of Health. | |||||
REF 4 | A phase II, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of MDX-1100, a fully human anti-CXCL10 monoclonal antibody, in combination with methotrexate in patients with rheumatoid arthritis. Arthritis Rheum. 2012 Jun;64(6):1730-9. | |||||
REF 5 | ClinicalTrials.gov (NCT01430429) Primary Biliary Cirrhosis: Investigating A New Treatment Option Using NI-0801, an Anti-CXCL10 Monoclonal Antibody. U.S. National Institutes of Health. | |||||
REF 6 | ClinicalTrials.gov (NCT04053283) First in Human Study With NG-641, an Oncolytic Transgene Expressing Adenoviral Vector. U.S. National Institutes of Health. | |||||
REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029267) | |||||
REF 8 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. |
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