Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT353XE3)

• DOT Name: C-X-C motif chemokine 11 (CXCL11)
• Synonyms: Beta-R1; H174; Interferon gamma-inducible protein 9; IP-9; Interferon-inducible T-cell alpha chemoattractant; I-TAC; Small-inducible cytokine B11
• Gene Name: CXCL11
• UniProt ID: CXL11_HUMAN
• PDB ID: 1RJT; 8HNK
• Pfam ID: PF00048
• Sequence:
  MSVKGMAIALAVILCATVVQGFPMFKRGRCLCIGPGVKAVKVADIEKASIMYPSNNCDKI
  EVIITLKENKGQRCLNPKSKQARLIIKKVERKNF
• Function: Chemotactic for interleukin-activated T-cells but not unstimulated T-cells, neutrophils or monocytes. Induces calcium release in activated T-cells. Binds to CXCR3. May play an important role in CNS diseases which involve T-cell recruitment. May play a role in skin immune responses.
• Tissue Specificity: High levels in peripheral blood leukocytes, pancreas and liver astrocytes. Moderate levels in thymus, spleen and lung. Low levels in placenta, prostate and small intestine. Also found in epidermal basal layer keratinocytes in skin disorders.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  Chemokine sig.ling pathway (hsa04062)
  Toll-like receptor sig.ling pathway (hsa04620)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Chemokine receptors bind chemokines (R-HSA-380108)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of C-X-C motif chemokine 11 (CXCL11).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of C-X-C motif chemokine 11 (CXCL11).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of C-X-C motif chemokine 11 (CXCL11).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of C-X-C motif chemokine 11 (CXCL11).	[4]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of C-X-C motif chemokine 11 (CXCL11).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of C-X-C motif chemokine 11 (CXCL11).	[6]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of C-X-C motif chemokine 11 (CXCL11).	[3]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of C-X-C motif chemokine 11 (CXCL11).	[7]
Malathion	DMXZ84M	Approved	Malathion increases the expression of C-X-C motif chemokine 11 (CXCL11).	[8]
Tofacitinib	DMBS370	Approved	Tofacitinib decreases the expression of C-X-C motif chemokine 11 (CXCL11).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of C-X-C motif chemokine 11 (CXCL11).	[10]
Jakafi	DMNORK8	Phase 3	Jakafi decreases the expression of C-X-C motif chemokine 11 (CXCL11).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of C-X-C motif chemokine 11 (CXCL11).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of C-X-C motif chemokine 11 (CXCL11).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of C-X-C motif chemokine 11 (CXCL11).	[13]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of C-X-C motif chemokine 11 (CXCL11).	[14]
Bilirubin	DMI0V4O	Investigative	Bilirubin increases the expression of C-X-C motif chemokine 11 (CXCL11).	[15]
Biotin	DMKMCE1	Investigative	Biotin decreases the expression of C-X-C motif chemokine 11 (CXCL11).	[16]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [3] Recruitment of uterine NK cells: induction of CXC chemokine ligands 10 and 11 in human endometrium by estradiol and progesterone. J Immunol. 2004 Dec 1;173(11):6760-6. doi: 10.4049/jimmunol.173.11.6760.
• [4] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [5] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [6] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [7] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [8] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [9] Regulation of inflammatory responses in tumor necrosis factor-activated and rheumatoid arthritis synovial macrophages by JAK inhibitors. Arthritis Rheum. 2012 Dec;64(12):3856-66. doi: 10.1002/art.37691.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Interleukin-24 as a target cytokine of environmental aryl hydrocarbon receptor agonist exposure in the lung. Toxicol Appl Pharmacol. 2017 Jun 1;324:1-11. doi: 10.1016/j.taap.2017.03.019. Epub 2017 Mar 27.
• [12] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [13] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.
• [14] Effects of paraquat and capsaicin on the expression of genes related to inflammatory, immune responses and cell death in immortalized human HaCat keratinocytes. Int J Immunopathol Pharmacol. 2011 Oct-Dec;24(4):861-8.
• [15] Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):73-88.
• [16] Clusters of biotin-responsive genes in human peripheral blood mononuclear cells. J Nutr Biochem. 2004 Jul;15(7):433-9.