Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE2DU0A)

• DOT Name: C-C motif chemokine 23 (CCL23)
• Synonyms: CK-beta-8; CKB-8; Macrophage inflammatory protein 3; MIP-3; Myeloid progenitor inhibitory factor 1; MPIF-1; Small-inducible cytokine A23
• Gene Name: CCL23
• UniProt ID: CCL23_HUMAN
• PDB ID: 1G91
• Pfam ID: PF00048
• Sequence:
  MKVSVAALSCLMLVTALGSQARVTKDAETEFMMSKLPLENPVLLDRFHATSADCCISYTP
  RSIPCSLLESYFETNSECSKPGVIFLTKKGRRFCANPSDKQVQVCMRMLKLDTRIKTRKN
• Function: Shows chemotactic activity for monocytes, resting T-lymphocytes, and neutrophils, but not for activated lymphocytes. Inhibits proliferation of myeloid progenitor cells in colony formation assays. This protein can bind heparin. Binds CCR1. CCL23(19-99), CCL23(22-99), CCL23(27-99), CCL23(30-99) are more potent chemoattractants than CCL23.
• Tissue Specificity: High levels in adult lung, liver, skeletal muscle and pancreas. Moderate levels in fetal liver, adult bone marrow and placenta. The short form is the major species and the longer form was detected only in very low abundance. CCL23(19-99), CCL23(22-99), CCL23(27-99), CCL23(30-99) are found in high levels in synovial fluids from rheumatoid patients.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  Chemokine sig.ling pathway (hsa04062)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of C-C motif chemokine 23 (CCL23).	[1]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of C-C motif chemokine 23 (CCL23).	[2]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of C-C motif chemokine 23 (CCL23).	[3]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of C-C motif chemokine 23 (CCL23).	[4]

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 increases the methylation of C-C motif chemokine 23 (CCL23).	[5]

References

• [1] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [2] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [3] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [4] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [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.