Details of Drug Off-Target (DOT)

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

• DOT Name: C-X-C motif chemokine 9 (CXCL9)
• Synonyms: Gamma-interferon-induced monokine; Monokine induced by interferon-gamma; HuMIG; MIG; Small-inducible cytokine B9
• Gene Name: CXCL9
• UniProt ID: CXCL9_HUMAN
• Pfam ID: PF00048
• Sequence:
  MKKSGVLFLLGIILLVLIGVQGTPVVRKGRCSCISTNQGTIHLQSLKDLKQFAPSPSCEK
  IEIIATLKNGVQTCLNPDSADVKELIKKWEKQVSQKKKQKNGKKHQKKKVLKVRKSQRSR
  QKKTT
• Function: Cytokine that affects the growth, movement, or activation state of cells that participate in immune and inflammatory response. Chemotactic for activated T-cells. Binds to CXCR3.
• 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

14 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-X-C motif chemokine 9 (CXCL9).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of C-X-C motif chemokine 9 (CXCL9).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of C-X-C motif chemokine 9 (CXCL9).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of C-X-C motif chemokine 9 (CXCL9).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of C-X-C motif chemokine 9 (CXCL9).	[5]
Marinol	DM70IK5	Approved	Marinol decreases the expression of C-X-C motif chemokine 9 (CXCL9).	[7]
Selenium	DM25CGV	Approved	Selenium decreases the expression of C-X-C motif chemokine 9 (CXCL9).	[8]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of C-X-C motif chemokine 9 (CXCL9).	[9]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of C-X-C motif chemokine 9 (CXCL9).	[10]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of C-X-C motif chemokine 9 (CXCL9).	[7]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of C-X-C motif chemokine 9 (CXCL9).	[11]
Tofacitinib	DMBS370	Approved	Tofacitinib decreases the expression of C-X-C motif chemokine 9 (CXCL9).	[12]
MLN4924	DMP36KD	Phase 3	MLN4924 affects the expression of C-X-C motif chemokine 9 (CXCL9).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of C-X-C motif chemokine 9 (CXCL9).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of C-X-C motif chemokine 9 (CXCL9).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of C-X-C motif chemokine 9 (CXCL9).	[14]

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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] 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.
• [5] Angiogenic potential of 3-nitro-4-hydroxy benzene arsonic acid (roxarsone). Environ Health Perspect. 2008 Apr;116(4):520-3.
• [6] Promoter methylation of PARG1, a novel candidate tumor suppressor gene in mantle-cell lymphomas. Haematologica. 2007 Apr;92(4):460-8. doi: 10.3324/haematol.10337.
• [7] Alcohol and Cannabinoids Differentially Affect HIV Infection and Function of Human Monocyte-Derived Dendritic Cells (MDDC). Front Microbiol. 2015 Dec 22;6:1452. doi: 10.3389/fmicb.2015.01452. eCollection 2015.
• [8] Selenium is critical for cancer-signaling gene expression but not cell proliferation in human colon Caco-2 cells. Biofactors. 2007;31(3-4):155-64. doi: 10.1002/biof.5520310302.
• [9] Effect of ovarian steroids on gene expression profile in human uterine microvascular endothelial cells. Fertil Steril. 2009 Aug;92(2):709-21.
• [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] Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
• [12] 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.
• [13] 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.
• [14] 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.