Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD49T9R)

• DOT Name: C-X-C motif chemokine 16 (CXCL16)
• Synonyms: Scavenger receptor for phosphatidylserine and oxidized low density lipoprotein; SR-PSOX; Small-inducible cytokine B16; Transmembrane chemokine CXCL16
• Gene Name: CXCL16
• Related Disease:
  Asthma
  Chronic renal failure
  End-stage renal disease
  Glioblastoma multiforme
  Acute coronary syndrome
  Breast cancer
  Breast carcinoma
  Carcinoma
  Colon cancer
  Colon carcinoma
  Epithelial ovarian cancer
  Glioma
  Lung cancer
  Lung carcinoma
  Metabolic disorder
  Metastatic malignant neoplasm
  Multiple sclerosis
  Obesity
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic cancer
  Prostate neoplasm
  Rheumatoid arthritis
  Systemic lupus erythematosus
  Vitiligo
  Bone osteosarcoma
  Cardiovascular disease
  Diabetic kidney disease
  Neoplasm
  Non-insulin dependent diabetes
  Osteosarcoma
  Pulmonary fibrosis
  Schizophrenia
  Non-alcoholic fatty liver disease
  Adult glioblastoma
  Advanced cancer
  Clear cell renal carcinoma
  Fatty liver disease
  Gastric cancer
  Hepatocellular carcinoma
  Melanoma
  Myocardial infarction
  Non-small-cell lung cancer
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Stomach cancer
• UniProt ID: CXL16_HUMAN
• Pfam ID: PF20902
• Sequence:
  MGRDLRPGSRVLLLLLLLLLVYLTQPGNGNEGSVTGSCYCGKRISSDSPPSVQFMNRLRK
  HLRAYHRCLYYTRFQLLSWSVCGGNKDPWVQELMSCLDLKECGHAYSGIVAHQKHLLPTS
  PPISQASEGASSDIHTPAQMLLSTLQSTQRPTLPVGSLSSDKELTRPNETTIHTAGHSLA
  AGPEAGENQKQPEKNAGPTARTSATVPVLCLLAIIFILTAALSYVLCKRRRGQSPQSSPD
  LPVHYIPVAPDSNT
• Function: Acts as a scavenger receptor on macrophages, which specifically binds to OxLDL (oxidized low density lipoprotein), suggesting that it may be involved in pathophysiology such as atherogenesis. Induces a strong chemotactic response. Induces calcium mobilization. Binds to CXCR6/Bonzo.
• Tissue Specificity: Expressed in T-cell areas. Expressed in spleen, lymph nodes, lung, kidney, small intestine and thymus. Weak expression in heart and liver and no expression in brain and bone marrow.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Chemokine sig.ling pathway (hsa04062)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Chemokine receptors bind chemokines (R-HSA-380108)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Definitive	Biomarker	[1]
Chronic renal failure	DISGG7K6	Definitive	Biomarker	[2]
End-stage renal disease	DISXA7GG	Definitive	Biomarker	[2]
Glioblastoma multiforme	DISK8246	Definitive	Altered Expression	[3]
Acute coronary syndrome	DIS7DYEW	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[5]
Carcinoma	DISH9F1N	Strong	Altered Expression	[6]
Colon cancer	DISVC52G	Strong	Altered Expression	[7]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[7]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[8]
Glioma	DIS5RPEH	Strong	Biomarker	[3]
Lung cancer	DISCM4YA	Strong	Biomarker	[9]
Lung carcinoma	DISTR26C	Strong	Biomarker	[9]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[10]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[11]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[12]
Obesity	DIS47Y1K	Strong	Genetic Variation	[13]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[8]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[8]
Pancreatic cancer	DISJC981	Strong	Biomarker	[14]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[15]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[16]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[17]
Vitiligo	DISR05SL	Strong	Biomarker	[18]
Bone osteosarcoma	DIST1004	moderate	Altered Expression	[19]
Cardiovascular disease	DIS2IQDX	moderate	Biomarker	[20]
Diabetic kidney disease	DISJMWEY	moderate	Biomarker	[21]
Neoplasm	DISZKGEW	moderate	Altered Expression	[7]
Non-insulin dependent diabetes	DISK1O5Z	moderate	Biomarker	[22]
Osteosarcoma	DISLQ7E2	moderate	Altered Expression	[19]
Pulmonary fibrosis	DISQKVLA	moderate	Biomarker	[23]
Schizophrenia	DISSRV2N	moderate	Biomarker	[20]
Non-alcoholic fatty liver disease	DISDG1NL	Disputed	Biomarker	[24]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[25]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[26]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[27]
Fatty liver disease	DIS485QZ	Limited	Biomarker	[28]
Gastric cancer	DISXGOUK	Limited	Biomarker	[29]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[30]
Melanoma	DIS1RRCY	Limited	Biomarker	[25]
Myocardial infarction	DIS655KI	Limited	Biomarker	[4]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[31]
Prostate cancer	DISF190Y	Limited	Biomarker	[32]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[32]
Renal cell carcinoma	DISQZ2X8	Limited	Biomarker	[27]
Stomach cancer	DISKIJSX	Limited	Biomarker	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of C-X-C motif chemokine 16 (CXCL16).	[33]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of C-X-C motif chemokine 16 (CXCL16).	[34]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of C-X-C motif chemokine 16 (CXCL16).	[35]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of C-X-C motif chemokine 16 (CXCL16).	[36]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of C-X-C motif chemokine 16 (CXCL16).	[37]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of C-X-C motif chemokine 16 (CXCL16).	[38]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of C-X-C motif chemokine 16 (CXCL16).	[39]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of C-X-C motif chemokine 16 (CXCL16).	[40]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of C-X-C motif chemokine 16 (CXCL16).	[41]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of C-X-C motif chemokine 16 (CXCL16).	[42]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of C-X-C motif chemokine 16 (CXCL16).	[43]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of C-X-C motif chemokine 16 (CXCL16).	[45]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of C-X-C motif chemokine 16 (CXCL16).	[44]

References

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• [13] The overweight increases circulating inflammatory mediators commonly associated with obesity in young individuals.Cytokine. 2018 Oct;110:169-173. doi: 10.1016/j.cyto.2018.04.024. Epub 2018 May 12.
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• [16] CXCL16 upregulates RANKL expression in rheumatoid arthritis synovial fibroblasts through the JAK2/STAT3 and p38/MAPK signaling pathway.Inflamm Res. 2016 Mar;65(3):193-202. doi: 10.1007/s00011-015-0905-y. Epub 2015 Nov 30.
• [17] Coordinated Induction of Antimicrobial Response Factors in Systemic Lupus Erythematosus.Front Immunol. 2019 Apr 4;10:658. doi: 10.3389/fimmu.2019.00658. eCollection 2019.
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• [21] Urinary chemokine C-X-C motif ligand 16 and endostatin as predictors of tubulointerstitial fibrosis in patients with advanced diabetic kidney disease.Nephrol Dial Transplant. 2021 Jan 25;36(2):295-305. doi: 10.1093/ndt/gfz168.
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• [23] CXCL16/CXCR6 axis promotes bleomycin-induced fibrotic process in MRC-5 cells via the PI3K/AKT/FOXO3a pathway.Int Immunopharmacol. 2020 Apr;81:106035. doi: 10.1016/j.intimp.2019.106035. Epub 2019 Nov 19.
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• [26] Plasma levels of the proangiogenic protein CXCL16 remains elevated for 1month after minimally invasive colorectal cancer resection.World J Surg Oncol. 2018 Jul 7;16(1):132. doi: 10.1186/s12957-018-1418-2.
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• [33] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
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• [35] All-trans retinoic acid regulates CXCL16/SR-PSOX expression. Int J Mol Med. 2005 Oct;16(4):661-5.
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• [37] 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.
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• [39] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
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• [44] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
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