Target Information

Target General Information

Target ID

T11309 (Former ID: TTDR00451)

Target Name

Monocyte chemotactic and activating factor (CCL2)

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

Target Type

Clinical trial target

[1]

Disease

[+] 1 Target-related Diseases

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

UniProt ID

CCL2_HUMAN

Sequence

MKVSAALLCLLLIAATFIPQGLAQPDAINAPVTCCYNFTNRKISVQRLASYRRITSSKCP
KEAVIFKTIVAKEICADPKQKWVQDSMDHLDKQTQTPKT

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3D Structure

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AlphaFold

HIT2.0 ID

T17UP9

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 2 Clinical Trial Drugs

Carlumab

Drug Info

Phase 2

Pulmonary fibrosis

[2], [3]

NOX-E36

Drug Info

Phase 2

Diabetic complication

[4]

Discontinued Drug(s)

[+] 1 Discontinued Drugs

ABN-912

Drug Info

Discontinued in Phase 1

Asthma

[6]

Mode of Action

[+] 1 Modes of Action

Inhibitor

[+] 1 Inhibitor drugs

NOX-E36

Drug Info

[9]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

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

Different Human System Profiles of Target

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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

There is no similarity protein (E value < 0.005) for this target

KEGG Pathway	Pathway ID	Affiliated Target
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
NOD-like receptor signaling pathway	hsa04621	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
IL-17 signaling pathway	hsa04657	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
TNF signaling pathway	hsa04668	Affiliated Target
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
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

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Target Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 9 KEGG Pathways

Cytokine-cytokine receptor interaction

Chemokine signaling pathway

NOD-like receptor signaling pathway

TNF signaling pathway

Chagas disease (American trypanosomiasis)

Malaria

Influenza A

Herpes simplex infection

Rheumatoid arthritis

NetPath Pathway

[+] 10 NetPath Pathways

IL9 Signaling Pathway

IL5 Signaling Pathway

IL1 Signaling Pathway

TSH Signaling Pathway

TWEAK Signaling Pathway

IL4 Signaling Pathway

TNFalpha Signaling Pathway

TSLP Signaling Pathway

Leptin Signaling Pathway

RANKL Signaling Pathway

Panther Pathway

[+] 1 Panther Pathways

Inflammation mediated by chemokine and cytokine signaling pathway

PID Pathway

[+] 4 PID Pathways

GMCSF-mediated signaling events

Validated transcriptional targets of AP1 family members Fra1 and Fra2

AP-1 transcription factor network

IL23-mediated signaling events

Reactome

[+] 2 Reactome Pathways

Chemokine receptors bind chemokines

ATF4 activates genes

WikiPathways

[+] 11 WikiPathways

IL1 and megakaryotyces in obesity

Activation of Genes by ATF4

Spinal Cord Injury

Oncostatin M Signaling Pathway

TNF alpha Signaling Pathway

TWEAK Signaling Pathway

IL-1 signaling pathway

GPCR ligand binding

Folate Metabolism

Vitamin B12 Metabolism

Selenium Micronutrient Network

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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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

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

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.

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