Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIKW21L)

• DOT Name: C-C motif chemokine 17 (CCL17)
• Synonyms: CC chemokine TARC; Small-inducible cytokine A17; Thymus and activation-regulated chemokine
• Gene Name: CCL17
• UniProt ID: CCL17_HUMAN
• PDB ID: 1NR2; 1NR4; 5WK3; 7S4N; 7SCV; 8FJ2; 8SKK
• Pfam ID: PF00048
• Sequence:
  MAPLKMLALVTLLLGASLQHIHAARGTNVGRECCLEYFKGAIPLRKLKTWYQTSEDCSRD
  AIVFVTVQGRAICSDPNNKRVKNAVKYLQSLERS
• Function: Chemokine, which displays chemotactic activity for T lymphocytes, preferentially Th2 cells, but not monocytes or granulocytes. Therefore plays an important role in a wide range of inflammatory and immunological processes. Acts by binding to CCR4 at T-cell surface. Mediates GM-CSF/CSF2-driven pain and inflammation. In the brain, required to maintain the typical, highly branched morphology of hippocampal microglia under homeostatic conditions. May be important for the appropriate adaptation of microglial morphology and synaptic plasticity to acute lipopolysaccharide (LPS)-induced neuroinflammation. Plays a role in wound healing, mainly by inducing fibroblast migration into the wound.
• Tissue Specificity: Constitutively expressed in thymus. Detected at lower levels in the lung, colon and small intestine . Expressed in stimulated peripheral blood mononuclear cells, but not in resting cells .
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  Chemokine sig.ling pathway (hsa04062)
  C-type lectin receptor sig.ling pathway (hsa04625)
  IL-17 sig.ling pathway (hsa04657)
• Reactome Pathway: Chemokine receptors bind chemokines (R-HSA-380108)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Dinoprostone	DMTYOPD	Approved	Dinoprostone increases the expression of C-C motif chemokine 17 (CCL17).	[1]
Budesonide	DMJIBAW	Approved	Budesonide decreases the expression of C-C motif chemokine 17 (CCL17).	[3]
Fexofenadine	DM17ONX	Approved	Fexofenadine decreases the expression of C-C motif chemokine 17 (CCL17).	[4]
MLN4924	DMP36KD	Phase 3	MLN4924 affects the expression of C-C motif chemokine 17 (CCL17).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of C-C motif chemokine 17 (CCL17).	[7]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Isoproterenol	DMK7MEY	Approved	Isoproterenol decreases the secretion of C-C motif chemokine 17 (CCL17).	[2]

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 affects the methylation of C-C motif chemokine 17 (CCL17).	[6]

References

• [1] Maturation of human monocyte-derived dendritic cells (MoDCs) in the presence of prostaglandin E2 optimizes CD4 and CD8 T cell-mediated responses to protein antigens: role of PGE2 in chemokine and cytokine expression by MoDCs. Int Immunol. 2005 Dec;17(12):1561-72. doi: 10.1093/intimm/dxh335. Epub 2005 Nov 22.
• [2] IL-13 and IL-4 promote TARC release in human airway smooth muscle cells: role of IL-4 receptor genotype. Am J Physiol Lung Cell Mol Physiol. 2003 Oct;285(4):L907-14. doi: 10.1152/ajplung.00120.2003. Epub 2003 Jul 18.
• [3] Effect of inhaled corticosteroid on an immunoreactive thymus and activation-regulated chemokine expression in the bronchial biopsies from asthmatics. Allergy. 2005 Mar;60(3):317-22. doi: 10.1111/j.1398-9995.2005.00694.x.
• [4] Effect of histamine H1 receptor antagonists on TARC/CCL17 and MDC/CCL22 production from CD14+ cells induced by antigenic stimulation in vitro. Int Arch Allergy Immunol. 2011;155(1):38-51. doi: 10.1159/000318720. Epub 2010 Nov 25.
• [5] The Nedd8-activating enzyme inhibitor MLN4924 thwarts microenvironment-driven NF-B activation and induces apoptosis in chronic lymphocytic leukemia B cells. Clin Cancer Res. 2014 Mar 15;20(6):1576-89. doi: 10.1158/1078-0432.CCR-13-0987.
• [6] 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.
• [7] Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression. Cell Rep. 2015 Sep 29;12(12):1986-96. doi: 10.1016/j.celrep.2015.08.046. Epub 2015 Sep 17.