Target Information
| Target General Information | Top | |||||
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| Target ID |
T11309
(Former ID: TTDR00451)
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| Target Name |
Monocyte chemotactic and activating factor (CCL2)
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| Synonyms |
Small-inducible cytokine A2; SCYA2; Monocyte secretory protein JE; Monocyte chemotactic protein 1; Monocyte chemoattractant protein-1; Monocyte Chemoattractant Protein 1; MCP1; MCP-1; MCAF; HC11; C-C motif chemokine 2
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| Gene Name |
CCL2
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Nephritic syndrome [ICD-11: GB40] | |||||
| Function |
Signals through binding and activation of CCR2 and induces a strong chemotactic response and mobilization of intracellular calcium ions. Exhibits a chemotactic activity for monocytes and basophils but not neutrophils or eosinophils. May be involved in the recruitment of monocytes into the arterial wall during the disease process of atherosclerosis. Acts as a ligand for C-C chemokine receptor CCR2.
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| BioChemical Class |
Cytokine: CC chemokine
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| UniProt ID | ||||||
| Sequence |
MKVSAALLCLLLIAATFIPQGLAQPDAINAPVTCCYNFTNRKISVQRLASYRRITSSKCP
KEAVIFKTIVAKEICADPKQKWVQDSMDHLDKQTQTPKT Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T17UP9 | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 4 Clinical Trial Drugs | + | ||||
| 1 | Bindarit | Drug Info | Phase 3 | Nephritis | [1] | |
| 2 | Carlumab | Drug Info | Phase 2 | Pulmonary fibrosis | [2], [3] | |
| 3 | NOX-E36 | Drug Info | Phase 2 | Diabetic complication | [4] | |
| 4 | CNTO888 | Drug Info | Phase 1 | Solid tumour/cancer | [5] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | ABN-912 | Drug Info | Discontinued in Phase 1 | Asthma | [6] | |
| Preclinical Drug(s) | [+] 2 Preclinical Drugs | + | ||||
| 1 | MCP-1 | Drug Info | Preclinical | Rheumatoid arthritis | [7] | |
| 2 | RS-504393 | Drug Info | Preclinical | Chronic obstructive pulmonary disease | [7], [8] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 4 Inhibitor drugs | + | ||||
| 1 | Bindarit | Drug Info | [1] | |||
| 2 | NOX-E36 | Drug Info | [9] | |||
| 3 | MCP-1 | Drug Info | [7] | |||
| 4 | RS-504393 | Drug Info | [7], [12] | |||
| 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 | ||
| NOD-like receptor signaling pathway | hsa04621 | 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 | 26 | Degree centrality | 2.79E-03 | Betweenness centrality | 4.72E-04 |
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| Closeness centrality | 2.26E-01 | Radiality | 1.40E+01 | Clustering coefficient | 4.34E-01 |
| Neighborhood connectivity | 2.93E+01 | Topological coefficient | 9.88E-02 | Eccentricity | 11 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Bindarit: an anti-inflammatory small molecule that modulates the NF B pathway. Cell Cycle. 2012 Jan 1;11(1):159-69. | |||||
| REF 2 | 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. (Ligand id: 771). | |||||
| REF 3 | Carlumab, an anti-C-C chemokine ligand 2 monoclonal antibody, in combination with four chemotherapy regimens for the treatment of patients with solid tumors: an open-label, multicenter phase 1b study. Target Oncol. 2015 Mar;10(1):111-23. | |||||
| REF 4 | ClinicalTrials.gov (NCT01547897) NOX-E36 in Patients With Type 2 Diabetes Mellitus and Albuminuria. U.S. National Institutes of Health. | |||||
| REF 5 | ClinicalTrials.gov (NCT00537368) First Study of the Safety of CNTO 888 in Patients With Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 6 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020409) | |||||
| REF 7 | Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91. | |||||
| REF 8 | 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. (Ligand id: 781). | |||||
| REF 9 | Crystal structure of a mirror-image L-RNA aptamer (Spiegelmer) in complex with the natural L-protein target CCL2. Nat Commun. 2015 Apr 22;6:6923. | |||||
| REF 10 | CCL2 as an important mediator of prostate cancer growth in vivo through the regulation of macrophage infiltration. Neoplasia. 2007 Jul;9(7):556-62. | |||||
| REF 11 | A randomized controlled trial with an anti-CCL2 (anti-monocyte chemotactic protein 1) monoclonal antibody in patients with rheumatoid arthritis. Arthritis Rheum. 2006 Aug;54(8):2387-92. | |||||
| REF 12 | Privileged structures: a useful concept for the rational design of new lead drug candidates. Mini Rev Med Chem. 2007 Nov;7(11):1108-19. | |||||
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