Details of Drug Off-Target (DOT)

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

DOT Name	C-X-C motif chemokine 17 (CXCL17)
Synonyms	6-Cys CXCL17; Dendritic cell and monocyte chemokine-like protein; DMC; VEGF coregulated chemokine 1
Gene Name	CXCL17
Related Disease	Atopic dermatitis ( ) Dermatitis ( ) Primary cutaneous T-cell lymphoma ( ) Psoriasis ( ) Skin disease ( ) Breast neoplasm ( ) Dyggve-Melchior-Clausen disease ( ) Epithelial ovarian cancer ( ) Genital herpes ( ) Glioblastoma multiforme ( ) Glioma ( ) Hepatocellular carcinoma ( ) Immunodeficiency ( ) Inflammatory bowel disease ( ) Lung adenocarcinoma ( ) Lung cancer ( ) Lung carcinoma ( ) Lung squamous cell carcinoma ( ) Metastatic malignant neoplasm ( ) Neoplasm ( ) Neuralgia ( ) Prostate cancer ( ) Prostate carcinoma ( ) Gastric cancer ( ) Stomach cancer ( ) Asthma ( ) Colon cancer ( ) Colon carcinoma ( ) Intellectual disability ( ) Psychotic disorder ( ) Schizophrenia ( ) Smith-McCort dysplasia ( )
UniProt ID	CXL17_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF15211
Sequence	MKVLISSLLLLLPLMLMSMVSSSLNPGVARGHRDRGQASRRWLQEGGQECECKDWFLRAP RRKFMTVSGLPKKQCPCDHFKGNVKKTRHQRHHRKPNKHSRACQQFLKQCQLRSFALPL
Function	Chemokine that acts as a chemoattractant for monocytes, macrophages and dendritic cells. Plays a role in angiogenesis and possibly in the development of tumors. Acts as an anti-inflammatory in the stomach. May play a role in the innate defense against infections. Activates the C-X-C chemokine receptor GPR35 to induce a rapid and transient rise in the level of intracellular calcium ions ; [4-Cys CXCL17]: Seems to exhibit much higher chemoattractant potency on monocytes and macrophages than 6-Cys CXCL17.
Tissue Specificity	Detected in trachea, stomach, lung and skeletal muscle. Detected in intestine and in normal and asthmatic lung (at protein level). Breast tumors showed 3- to 24-fold up-regulation.
KEGG Pathway	Cytokine-cytokine receptor interaction (hsa04060 )

Molecular Interaction Atlas (MIA) of This DOT

32 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Atopic dermatitis	DISTCP41	Definitive	Altered Expression	[1]
Dermatitis	DISY5SZC	Definitive	Biomarker	[1]
Primary cutaneous T-cell lymphoma	DIS35WVW	Definitive	Altered Expression	[1]
Psoriasis	DIS59VMN	Definitive	Altered Expression	[1]
Skin disease	DISDW8R6	Definitive	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[2]
Dyggve-Melchior-Clausen disease	DISLC4FL	Strong	Genetic Variation	[3]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[4]
Genital herpes	DISAP666	Strong	Biomarker	[5]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[6]
Glioma	DIS5RPEH	Strong	Biomarker	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[7]
Immunodeficiency	DIS093I0	Strong	Biomarker	[8]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[9]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[10]
Lung cancer	DISCM4YA	Strong	Altered Expression	[10]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[10]
Lung squamous cell carcinoma	DISXPIBD	Strong	Altered Expression	[10]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[11]
Neuralgia	DISWO58J	Strong	Biomarker	[12]
Prostate cancer	DISF190Y	Strong	Biomarker	[13]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[13]
Gastric cancer	DISXGOUK	moderate	Biomarker	[14]
Stomach cancer	DISKIJSX	moderate	Biomarker	[14]
Asthma	DISW9QNS	Disputed	Biomarker	[15]
Colon cancer	DISVC52G	Limited	Altered Expression	[9]
Colon carcinoma	DISJYKUO	Limited	Altered Expression	[9]
Intellectual disability	DISMBNXP	Limited	Biomarker	[3]
Psychotic disorder	DIS4UQOT	Limited	Biomarker	[16]
Schizophrenia	DISSRV2N	Limited	Biomarker	[16]
Smith-McCort dysplasia	DIS18P12	Limited	Genetic Variation	[3]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of C-X-C motif chemokine 17 (CXCL17).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of C-X-C motif chemokine 17 (CXCL17).	[19]
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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-X-C motif chemokine 17 (CXCL17).	[18]
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References

1	CXCL17 Attenuates Imiquimod-Induced Psoriasis-like Skin Inflammation by Recruiting Myeloid-Derived Suppressor Cells and Regulatory T Cells.J Immunol. 2017 May 15;198(10):3897-3908. doi: 10.4049/jimmunol.1601607. Epub 2017 Apr 7.
2	VCC-1, a novel chemokine, promotes tumor growth.Biochem Biophys Res Commun. 2006 Nov 10;350(1):74-81. doi: 10.1016/j.bbrc.2006.08.194. Epub 2006 Sep 12.
3	Additional three patients with Smith-McCort dysplasia due to novel RAB33B mutations.Am J Med Genet A. 2017 Mar;173(3):588-595. doi: 10.1002/ajmg.a.38064. Epub 2017 Jan 27.
4	Tumor cell expression of B7-H4 correlates with higher frequencies of tumor-infiltrating APCs and higher CXCL17 expression in human epithelial ovarian cancer.Oncoimmunology. 2019 Sep 30;8(12):e1665460. doi: 10.1080/2162402X.2019.1665460. eCollection 2019.
5	CXCL17 Chemokine-Dependent Mobilization of CXCR8(+)CD8(+) Effector Memory and Tissue-Resident Memory T Cells in the Vaginal Mucosa Is Associated with Protection against Genital Herpes.J Immunol. 2018 Apr 15;200(8):2915-2926. doi: 10.4049/jimmunol.1701474. Epub 2018 Mar 16.
6	Proteasome mediated degradation of CDC25C and Cyclin B1 in Demethoxycurcumin treated human glioma U87 MG cells to trigger G2/M cell cycle arrest.Toxicol Appl Pharmacol. 2018 Oct 1;356:76-89. doi: 10.1016/j.taap.2018.07.012. Epub 2018 Aug 4.
7	CXCL17 promotes cell metastasis and inhibits autophagy via the LKB1-AMPK pathway in hepatocellular carcinoma.Gene. 2019 Mar 30;690:129-136. doi: 10.1016/j.gene.2018.12.043. Epub 2018 Dec 28.
8	CXCL17 expression by tumor cells recruits CD11b+Gr1 high F4/80- cells and promotes tumor progression.PLoS One. 2012;7(8):e44080. doi: 10.1371/journal.pone.0044080. Epub 2012 Aug 29.
9	Lymph node CXCL17 messenger RNA: A new prognostic biomarker for colon cancer.Tumour Biol. 2018 Sep;40(9):1010428318799251. doi: 10.1177/1010428318799251.
10	Mechanism of lung adenocarcinoma spine metastasis induced by CXCL17.Cell Oncol (Dordr). 2020 Apr;43(2):311-320. doi: 10.1007/s13402-019-00491-7. Epub 2019 Dec 12.
11	Establishment of a novel cancer cell line derived from vulvar carcinoma associated with lichen sclerosus exhibiting a fibroblast-dependent tumorigenic potential.Exp Cell Res. 2020 Jan 1;386(1):111684. doi: 10.1016/j.yexcr.2019.111684. Epub 2019 Oct 23.
12	Kynurenic acid and zaprinast diminished CXCL17-evoked pain-related behaviour and enhanced morphine analgesia in a mouse neuropathic pain model.Pharmacol Rep. 2019 Feb;71(1):139-148. doi: 10.1016/j.pharep.2018.10.002. Epub 2018 Oct 6.
13	Demethoxycurcumin: A naturally occurring curcumin analogue with antitumor properties.J Cell Physiol. 2018 Dec;233(12):9247-9260. doi: 10.1002/jcp.27029. Epub 2018 Aug 4.
14	Gastric Cancer Associated Genes Identified by an Integrative Analysis of Gene Expression Data.Biomed Res Int. 2017;2017:7259097. doi: 10.1155/2017/7259097. Epub 2017 Jan 23.
15	Decreased epithelial and sputum miR-221-3p associates with airway eosinophilic inflammation and CXCL17 expression in asthma.Am J Physiol Lung Cell Mol Physiol. 2018 Aug 1;315(2):L253-L264. doi: 10.1152/ajplung.00567.2017. Epub 2018 Apr 12.
16	Unwell in hospital but not incapable: cross-sectional study on the dissociation of decision-making capacity for treatment and research in in-patients with schizophrenia and related psychoses.Br J Psychiatry. 2018 Aug;213(2):484-489. doi: 10.1192/bjp.2018.85. Epub 2018 Jun 18.
17	Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
18	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.
19	Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.