Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSCMH06)

• DOT Name: C-C chemokine receptor type 8 (CCR8)
• Synonyms: C-C CKR-8; CC-CKR-8; CCR-8; CC chemokine receptor CHEMR1; CMKBRL2; Chemokine receptor-like 1; CKR-L1; GPR-CY6; GPRCY6; TER1; CD antigen CDw198
• Gene Name: CCR8
• UniProt ID: CCR8_HUMAN
• Pfam ID: PF00001
• Sequence:
  MDYTLDLSVTTVTDYYYPDIFSSPCDAELIQTNGKLLLAVFYCLLFVFSLLGNSLVILVL
  VVCKKLRSITDVYLLNLALSDLLFVFSFPFQTYYLLDQWVFGTVMCKVVSGFYYIGFYSS
  MFFITLMSVDRYLAVVHAVYALKVRTIRMGTTLCLAVWLTAIMATIPLLVFYQVASEDGV
  LQCYSFYNQQTLKWKIFTNFKMNILGLLIPFTIFMFCYIKILHQLKRCQNHNKTKAIRLV
  LIVVIASLLFWVPFNVVLFLTSLHSMHILDGCSISQQLTYATHVTEIISFTHCCVNPVIY
  AFVGEKFKKHLSEIFQKSCSQIFNYLGRQMPRESCEKSSSCQQHSSRSSSVDYIL
• Function: Receptor for the chemokine CCL1/SCYA1/I-309. May regulate monocyte chemotaxis and thymic cell line apoptosis. Alternative coreceptor with CD4 for HIV-1 infection.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  Chemokine sig.ling pathway (hsa04062)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Viral carcinogenesis (hsa05203)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Chemokine receptors bind chemokines (R-HSA-380108)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of C-C chemokine receptor type 8 (CCR8).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of C-C chemokine receptor type 8 (CCR8).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of C-C chemokine receptor type 8 (CCR8).	[2]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of C-C chemokine receptor type 8 (CCR8).	[3]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of C-C chemokine receptor type 8 (CCR8).	[4]

References

• [1] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [2] Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling. Toxicol Sci. 2014 Jun;139(2):328-37. doi: 10.1093/toxsci/kfu053. Epub 2014 Mar 27.
• [3] Gene expression profile induced by arsenic trioxide in chronic lymphocytic leukemia cells reveals a central role for heme oxygenase-1 in apoptosis and regulation of matrix metalloproteinase-9. Oncotarget. 2016 Dec 13;7(50):83359-83377.
• [4] Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors. Leuk Res. 2007 Nov;31(11):1511-20.
• [5] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.