Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLSZR00)

• DOT Name: Tumor-associated calcium signal transducer 2 (TACSTD2)
• Synonyms: Cell surface glycoprotein Trop-2; Membrane component chromosome 1 surface marker 1; Pancreatic carcinoma marker protein GA733-1
• Gene Name: TACSTD2
• Related Disease: Gelatinous drop-like corneal dystrophy
• UniProt ID: TACD2_HUMAN
• PDB ID: 2MAE; 2MVK; 2MVL; 7E5M; 7E5N; 7PEE
• Pfam ID: PF21283 ; PF18635 ; PF00086
• Sequence:
  MARGPGLAPPPLRLPLLLLVLAAVTGHTAAQDNCTCPTNKMTVCSPDGPGGRCQCRALGS
  GMAVDCSTLTSKCLLLKARMSAPKNARTLVRPSEHALVDNDGLYDPDCDPEGRFKARQCN
  QTSVCWCVNSVGVRRTDKGDLSLRCDELVRTHHILIDLRHRPTAGAFNHSDLDAELRRLF
  RERYRLHPKFVAAVHYEQPTIQIELRQNTSQKAAGDVDIGDAAYYFERDIKGESLFQGRG
  GLDLRVRGEPLQVERTLIYYLDEIPPKFSMKRLTAGLIAVIVVVVVALVAGMAVLVITNR
  RKSGKYKKVEIKELGELRKEPSL
• Function: May function as a growth factor receptor.
• Tissue Specificity: Placenta, pancreatic carcinoma cell lines.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gelatinous drop-like corneal dystrophy	DISEWOEY	Definitive	Autosomal recessive	[1]

24 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 Tumor-associated calcium signal transducer 2 (TACSTD2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[11]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[12]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[9]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[4]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[13]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[14]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[4]
Coprexa	DMA0WEK	Phase 3	Coprexa decreases the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[15]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[5]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[17]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 decreases the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[18]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Tumor-associated calcium signal transducer 2 (TACSTD2).	[19]

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 decreases the methylation of Tumor-associated calcium signal transducer 2 (TACSTD2).	[16]

References

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• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro. J Invest Dermatol. 2005 Jul;125(1):143-53.
• [5] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [6] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [7] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [8] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [9] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [10] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [11] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [12] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [13] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [14] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [15] Copper deprivation enhances the chemosensitivity of pancreatic cancer to rapamycin by mTORC1/2 inhibition. Chem Biol Interact. 2023 Sep 1;382:110546. doi: 10.1016/j.cbi.2023.110546. Epub 2023 Jun 7.
• [16] 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.
• [17] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [18] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [19] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.