Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT52AOIG)

• DOT Name: Thymic stromal lymphopoietin (TSLP)
• Gene Name: TSLP
• UniProt ID: TSLP_HUMAN
• PDB ID: 5J11; 5J12; 5J13
• Pfam ID: PF15216
• Sequence:
  MFPFALLYVLSVSFRKIFILQLVGLVLTYDFTNCDFEKIKAAYLSTISKDLITYMSGTKS
  TEFNNTVSCSNRPHCLTEIQSLTFNPTAGCASLAKEMFAMKTKAALAIWCPGYSETQINA
  TQAMKKRRKRKVTTNKCLEQVSQLQGLWRRFNRPLLKQQ
• Function: [Isoform 1]: Cytokine that induces the release of T-cell-attracting chemokines from monocytes and, in particular, enhances the maturation of CD11c(+) dendritic cells. Can induce allergic inflammation by directly activating mast cells; [Isoform 2]: May act as an antimicrobial peptide in the oral cavity and on the skin.
• Tissue Specificity: Isoform 1 is expressed in a number of tissues including heart, liver and prostate. Isoform 2 is the predominant form in keratinocytes of oral mucosa, skin and in salivary glands. It is secreted into saliva.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  JAK-STAT sig.ling pathway (hsa04630)
• Reactome Pathway: Interleukin-7 signaling (R-HSA-1266695)

Molecular Interaction Atlas (MIA) of This DOT

17 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 Thymic stromal lymphopoietin (TSLP).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Thymic stromal lymphopoietin (TSLP).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Thymic stromal lymphopoietin (TSLP).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Thymic stromal lymphopoietin (TSLP).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Thymic stromal lymphopoietin (TSLP).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Thymic stromal lymphopoietin (TSLP).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Thymic stromal lymphopoietin (TSLP).	[7]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Thymic stromal lymphopoietin (TSLP).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Thymic stromal lymphopoietin (TSLP).	[9]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Thymic stromal lymphopoietin (TSLP).	[10]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Thymic stromal lymphopoietin (TSLP).	[11]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Thymic stromal lymphopoietin (TSLP).	[12]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Thymic stromal lymphopoietin (TSLP).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Thymic stromal lymphopoietin (TSLP).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Thymic stromal lymphopoietin (TSLP).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Thymic stromal lymphopoietin (TSLP).	[17]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Thymic stromal lymphopoietin (TSLP).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Thymic stromal lymphopoietin (TSLP).	[16]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] 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.
• [6] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [7] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [8] Triclosan Induces Thymic Stromal Lymphopoietin in Skin Promoting Th2 Allergic Responses. Toxicol Sci. 2015 Sep;147(1):127-39. doi: 10.1093/toxsci/kfv113. Epub 2015 Jun 5.
• [9] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [10] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [11] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [12] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [13] Diesel exhaust particle-exposed human bronchial epithelial cells induce dendritic cell maturation and polarization via thymic stromal lymphopoietin. J Clin Immunol. 2008 Mar;28(2):147-56. doi: 10.1007/s10875-007-9149-0. Epub 2007 Nov 30.
• [14] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [15] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [16] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [17] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [18] A critical role for thymic stromal lymphopoietin in nickel-induced allergy in mice. J Immunol. 2014 May 1;192(9):4025-31. doi: 10.4049/jimmunol.1300276. Epub 2014 Mar 26.