Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTNAY0P)

• DTT 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
• Gene Name: CCL2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Cytokine: CC chemokine
• UniProt ID: CCL2_HUMAN
• TTD ID: T11309
• Sequence:
  MKVSAALLCLLLIAATFIPQGLAQPDAINAPVTCCYNFTNRKISVQRLASYRRITSSKCP
  KEAVIFKTIVAKEICADPKQKWVQDSMDHLDKQTQTPKT
• 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.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Chemokine signaling pathway (hsa04062)
  NOD-like receptor signaling pathway (hsa04621)
  TNF signaling pathway (hsa04668)
  Chagas disease (American trypanosomiasis) (hsa05142)
  Malaria (hsa05144)
  Influenza A (hsa05164)
  Herpes simplex infection (hsa05168)
  Rheumatoid arthritis (hsa05323)
• Reactome Pathway:
  ATF4 activates genes (R-HSA-380994)
  Chemokine receptors bind chemokines (R-HSA-380108)

Molecular Interaction Atlas (MIA) of This DTT

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bindarit	DMS2GA1	Nephritis	GB40	Phase 3	[1]
Carlumab	DMAUN15	Pulmonary fibrosis	CB03.4	Phase 2	[2]
NOX-E36	DMHG3UR	Diabetic complication	5A2Y	Phase 2	[3]
CNTO888	DMUBP0V	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ABN-912	DMADKHB	Asthma	CA23	Discontinued in Phase 1	[5]

2 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MCP-1	DMYEFKH	Rheumatoid arthritis	FA20	Preclinical	[6]
RS-504393	DMB9IPR	Chronic obstructive pulmonary disease	CA22	Preclinical	[7]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Rheumatoid arthritis	FA20	Synovial tissue	3.76E-06	3.57	4.42
Chronic obstructive pulmonary disease	CA23	Lung tissue	3.77E-02	0.79	0.56
Chronic obstructive pulmonary disease	CA23	Small airway epithelium	9.17E-07	1.32	1.24
Asthma	CA23	Nasal and bronchial airway	1.98E-02	0.07	0.1
Idiopathic pulmonary fibrosis	CA23	Lung tissue	2.07E-01	-0.66	-0.49

References

• [1] Bindarit: an anti-inflammatory small molecule that modulates the NF B pathway. Cell Cycle. 2012 Jan 1;11(1):159-69.
• [2] 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.
• [3] 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.
• [4] CCL2 as an important mediator of prostate cancer growth in vivo through the regulation of macrophage infiltration. Neoplasia. 2007 Jul;9(7):556-62.
• [5] 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.
• [6] Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
• [7] Privileged structures: a useful concept for the rational design of new lead drug candidates. Mini Rev Med Chem. 2007 Nov;7(11):1108-19.