Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ7T10J)

• DOT Name: C-C chemokine receptor type 2 (CCR2)
• Synonyms: C-C CKR-2; CC-CKR-2; CCR-2; CCR2; Monocyte chemoattractant protein 1 receptor; MCP-1-R; CD antigen CD192
• Gene Name: CCR2
• UniProt ID: CCR2_HUMAN
• PDB ID: 2MLO; 2MLQ; 5T1A; 7P8X; 7XA3
• Pfam ID: PF00001
• Sequence:
  MLSTSRSRFIRNTNESGEEVTTFFDYDYGAPCHKFDVKQIGAQLLPPLYSLVFIFGFVGN
  MLVVLILINCKKLKCLTDIYLLNLAISDLLFLITLPLWAHSAANEWVFGNAMCKLFTGLY
  HIGYFGGIFFIILLTIDRYLAIVHAVFALKARTVTFGVVTSVITWLVAVFASVPGIIFTK
  CQKEDSVYVCGPYFPRGWNNFHTIMRNILGLVLPLLIMVICYSGILKTLLRCRNEKKRHR
  AVRVIFTIMIVYFLFWTPYNIVILLNTFQEFFGLSNCESTSQLDQATQVTETLGMTHCCI
  NPIIYAFVGEKFRSLFHIALGCRIAPLQKPVCGGPGVRPGKNVKVTTQGLLDGRGKGKSI
  GRAPEASLQDKEGA
• Function: Key functional receptor for CCL2 but can also bind CCL7 and CCL12. Its binding with CCL2 on monocytes and macrophages mediates chemotaxis and migration induction through the activation of the PI3K cascade, the small G protein Rac and lamellipodium protrusion (Probable). Also acts as a receptor for the beta-defensin DEFB106A/DEFB106B. Regulates the expression of T-cell inflammatory cytokines and T-cell differentiation, promoting the differentiation of T-cells into T-helper 17 cells (Th17) during inflammation. Facilitates the export of mature thymocytes by enhancing directional movement of thymocytes to sphingosine-1-phosphate stimulation and up-regulation of S1P1R expression; signals through the JAK-STAT pathway to regulate FOXO1 activity leading to an increased expression of S1P1R. Plays an important role in mediating peripheral nerve injury-induced neuropathic pain. Increases NMDA-mediated synaptic transmission in both dopamine D1 and D2 receptor-containing neurons, which may be caused by MAPK/ERK-dependent phosphorylation of GRIN2B/NMDAR2B. Mediates the recruitment of macrophages and monocytes to the injury site following brain injury; (Microbial infection) Alternative coreceptor with CD4 for HIV-1 infection.
• Tissue Specificity: Expressed by monocytes and IL2-activated NK cells.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  Chemokine sig.ling pathway (hsa04062)
• Reactome Pathway:
  Chemokine receptors bind chemokines (R-HSA-380108)
  G alpha (i) signalling events (R-HSA-418594)
  Interleukin-10 signaling (R-HSA-6783783)
  Beta defensins (R-HSA-1461957)

Molecular Interaction Atlas (MIA) of This DOT

22 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of C-C chemokine receptor type 2 (CCR2).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of C-C chemokine receptor type 2 (CCR2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of C-C chemokine receptor type 2 (CCR2).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of C-C chemokine receptor type 2 (CCR2).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of C-C chemokine receptor type 2 (CCR2).	[5]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of C-C chemokine receptor type 2 (CCR2).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of C-C chemokine receptor type 2 (CCR2).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of C-C chemokine receptor type 2 (CCR2).	[8]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of C-C chemokine receptor type 2 (CCR2).	[9]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of C-C chemokine receptor type 2 (CCR2).	[10]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of C-C chemokine receptor type 2 (CCR2).	[11]
Nefazodone	DM4ZS8M	Approved	Nefazodone increases the expression of C-C chemokine receptor type 2 (CCR2).	[12]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of C-C chemokine receptor type 2 (CCR2).	[13]
DNCB	DMDTVYC	Phase 2	DNCB decreases the expression of C-C chemokine receptor type 2 (CCR2).	[14]
Disulfiram	DMCL2OK	Phase 2 Trial	Disulfiram increases the expression of C-C chemokine receptor type 2 (CCR2).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of C-C chemokine receptor type 2 (CCR2).	[17]
Eugenol	DM7US1H	Patented	Eugenol decreases the expression of C-C chemokine receptor type 2 (CCR2).	[14]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of C-C chemokine receptor type 2 (CCR2).	[18]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of C-C chemokine receptor type 2 (CCR2).	[19]
NSC-1771	DMNXDGQ	Investigative	NSC-1771 decreases the expression of C-C chemokine receptor type 2 (CCR2).	[20]
PAF	DMRZAQW	Investigative	PAF increases the expression of C-C chemokine receptor type 2 (CCR2).	[21]
Oxindole 94	DMPFD6Y	Investigative	Oxindole 94 decreases the expression of C-C chemokine receptor type 2 (CCR2).	[11]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of C-C chemokine receptor type 2 (CCR2).	[16]

References

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• [13] Resveratrol inhibits expression and binding activity of the monocyte chemotactic protein-1 receptor, CCR2, on THP-1 monocytes. Atherosclerosis. 2007 Nov;195(1):e125-33. doi: 10.1016/j.atherosclerosis.2007.03.039. Epub 2007 May 17.
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• [18] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
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