Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT3QJC2)

• DOT Name: C-C motif chemokine 22 (CCL22)
• Synonyms: CC chemokine STCP-1; MDC(1-69); Macrophage-derived chemokine; Small-inducible cytokine A22; Stimulated T-cell chemotactic protein 1
• Gene Name: CCL22
• UniProt ID: CCL22_HUMAN
• Pfam ID: PF00048
• Sequence:
  MDRLQTALLVVLVLLAVALQATEAGPYGANMEDSVCCRDYVRYRLPLRVVKHFYWTSDSC
  PRPGVVLLTFRDKEICADPRVPWVKMILNKLSQ
• Function: May play a role in the trafficking of activated/effector T-lymphocytes to inflammatory sites and other aspects of activated T-lymphocyte physiology. Chemotactic for monocytes, dendritic cells and natural killer cells. Mild chemoattractant for primary activated T-lymphocytes and a potent chemoattractant for chronically activated T-lymphocytes but has no chemoattractant activity for neutrophils, eosinophils, and resting T-lymphocytes. Binds to CCR4. Processed forms MDC(3-69), MDC(5-69) and MDC(7-69) seem not be active.
• Tissue Specificity: Highly expressed in macrophage and in monocyte-derived dendritic cells, and thymus. Also found in lymph node, appendix, activated monocytes, resting and activated macrophages. Lower expression in lung and spleen. Very weak expression in small intestine. In lymph node expressed in a mature subset of Langerhans' cells (CD1a+ and CD83+). Expressed in Langerhans' cell histiocytosis but not in dermatopathic lymphadenopathy. Expressed in atopic dermatitis, allergic contact dermatitis skin, and psoriasis, in both the epidermis and dermis.
• 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)
• Reactome Pathway:
  Interleukin-10 signaling (R-HSA-6783783)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Chemokine receptors bind chemokines (R-HSA-380108)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	C-C motif chemokine 22 (CCL22) decreases the response to substance of Arsenic.	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of C-C motif chemokine 22 (CCL22).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of C-C motif chemokine 22 (CCL22).	[2]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of C-C motif chemokine 22 (CCL22).	[3]
Dinoprostone	DMTYOPD	Approved	Dinoprostone increases the expression of C-C motif chemokine 22 (CCL22).	[4]
Fexofenadine	DM17ONX	Approved	Fexofenadine decreases the expression of C-C motif chemokine 22 (CCL22).	[5]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of C-C motif chemokine 22 (CCL22).	[6]
MLN4924	DMP36KD	Phase 3	MLN4924 affects the expression of C-C motif chemokine 22 (CCL22).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of C-C motif chemokine 22 (CCL22).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of C-C motif chemokine 22 (CCL22).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of C-C motif chemokine 22 (CCL22).	[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 affects the methylation of C-C motif chemokine 22 (CCL22).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the secretion of C-C motif chemokine 22 (CCL22).	[12]

References

• [1] Antiepileptic drugs are endocrine disruptors for the human fetal testis ex vivo. Toxicol Sci. 2023 Sep 28;195(2):169-183. doi: 10.1093/toxsci/kfad076.
• [2] Chemokine induction by all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia: triggering the differentiation syndrome. Blood. 2009 Dec 24;114(27):5512-21. doi: 10.1182/blood-2009-02-204834. Epub 2009 Oct 14.
• [3] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [4] 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.
• [5] 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.
• [6] Grape resveratrol increases serum adiponectin and downregulates inflammatory genes in peripheral blood mononuclear cells: a triple-blind, placebo-controlled, one-year clinical trial in patients with stable coronary artery disease. Cardiovasc Drugs Ther. 2013 Feb;27(1):37-48. doi: 10.1007/s10557-012-6427-8.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [12] Ni(II) ions dysregulate cytokine secretion from human monocytes. J Biomed Mater Res B Appl Biomater. 2009 Feb;88(2):358-65. doi: 10.1002/jbm.b.31063.
• [13] Gene expression levels in normal human lymphoblasts with variable sensitivities to arsenite: identification of GGT1 and NFKBIE expression levels as possible biomarkers of susceptibility. Toxicol Appl Pharmacol. 2008 Jan 15;226(2):199-205. doi: 10.1016/j.taap.2007.09.004. Epub 2007 Sep 15.