Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3BIFPK)

• DOT Name: Eotaxin (CCL11)
• Synonyms: C-C motif chemokine 11; Eosinophil chemotactic protein; Small-inducible cytokine A11
• Gene Name: CCL11
• UniProt ID: CCL11_HUMAN
• PDB ID: 1EOT; 2EOT; 2MPM; 7SCS
• Pfam ID: PF00048
• Sequence:
  MKVSAALLWLLLIAAAFSPQGLAGPASVPTTCCFNLANRKIPLQRLESYRRITSGKCPQK
  AVIFKTKLAKDICADPKKKWVQDSMKYLDQKSPTPKP
• Function: In response to the presence of allergens, this protein directly promotes the accumulation of eosinophils, a prominent feature of allergic inflammatory reactions. Binds to CCR3.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  Chemokine sig.ling pathway (hsa04062)
  IL-17 sig.ling pathway (hsa04657)
  Asthma (hsa05310)
• Reactome Pathway:
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Chemokine receptors bind chemokines (R-HSA-380108)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Eotaxin (CCL11).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Eotaxin (CCL11).	[2]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Eotaxin (CCL11).	[3]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Eotaxin (CCL11).	[4]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the activity of Eotaxin (CCL11).	[5]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Eotaxin (CCL11).	[6]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Eotaxin (CCL11).	[7]
Tacrolimus	DMZ7XNQ	Approved	Tacrolimus decreases the expression of Eotaxin (CCL11).	[8]
Prednisone	DM2HG4X	Approved	Prednisone decreases the expression of Eotaxin (CCL11).	[9]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Eotaxin (CCL11).	[10]
JWH-015	DMGTSCP	Patented	JWH-015 decreases the expression of Eotaxin (CCL11).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Eotaxin (CCL11).	[13]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Eotaxin (CCL11).	[14]
Benzoquinone	DMNBA0G	Investigative	Benzoquinone increases the expression of Eotaxin (CCL11).	[6]
Piceatannol	DMYOP45	Investigative	Piceatannol decreases the expression of Eotaxin (CCL11).	[10]
Catechol	DML0YEK	Investigative	Catechol increases the expression of Eotaxin (CCL11).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Chloroquine	DMSI5CB	Phase 3 Trial	Chloroquine decreases the secretion of Eotaxin (CCL11).	[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 increases the methylation of Eotaxin (CCL11).	[12]

References

• [1] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [2] 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.
• [3] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [4] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [5] Expression of PPARgamma in eosinophils and its functional role in survival and chemotaxis. Immunol Lett. 2003 Apr 3;86(2):183-9. doi: 10.1016/s0165-2478(03)00003-8.
• [6] Identification of human cell responses to benzene and benzene metabolites. Genomics. 2007 Sep;90(3):324-33.
• [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] Tacrolimus decreases the expression of eotaxin, CCR3, RANTES and interleukin-5 in atopic dermatitis. Br J Dermatol. 2005 Jun;152(6):1173-81. doi: 10.1111/j.1365-2133.2005.06474.x.
• [9] Alterations in eotaxin, monocyte chemoattractant protein-4, interleukin-5, and interleukin-13 after systemic steroid treatment for nasal polyps. Otolaryngol Head Neck Surg. 2004 Nov;131(5):585-9. doi: 10.1016/j.otohns.2004.05.028.
• [10] Control of eotaxin-1 expression and release by resveratrol and its metabolites in culture human pulmonary artery endothelial cells. Am J Cardiovasc Dis. 2011;1(1):16-30. Epub 2011 Apr 26.
• [11] Paradoxical Effect of Chloroquine Treatment in Enhancing Chikungunya Virus Infection. Viruses. 2018 May 17;10(5):268. doi: 10.3390/v10050268.
• [12] 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.
• [13] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [14] Microarray Analysis of Gene Expression Alteration in Human Middle Ear Epithelial Cells Induced by Asian Sand Dust. Clin Exp Otorhinolaryngol. 2015 Dec;8(4):345-53. doi: 10.3342/ceo.2015.8.4.345. Epub 2015 Nov 10.