Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ574EY)

• DOT Name: Prostate stem cell antigen (PSCA)
• Gene Name: PSCA
• UniProt ID: PSCA_HUMAN
• Pfam ID: PF00021
• Sequence:
  MAGLALQPGTALLCYSCKAQVSNEDCLQVENCTQLGEQCWTARIRAVGLLTVISKGCSLN
  CVDDSQDYYVGKKNITCCDTDLCNASGAHALQPAAAILALLPALGLLLWGPGQL
• Function: May be involved in the regulation of cell proliferation. Has a cell-proliferation inhibition activity in vitro; May act as a modulator of nicotinic acetylcholine receptors (nAChRs) activity. In vitro inhibits nicotine-induced signaling probably implicating alpha-3:beta-2- or alpha-7-containing nAChRs.
• Tissue Specificity: Highly expressed in prostate (basal, secretory and neuroendocrine epithelium cells). Also found in bladder (transitional epithelium), placenta (trophoblasts), stomach (neuroendocrine cells), colon (neuroendocrine cells) and kidney (collecting ducts). Overexpressed in prostate cancers and expression is correlated with tumor stage, grade and androgen-independence. Highly expressed in prostate cancer bone metastases. Expressed in gastric epithelial cells, mainly in the isthmus (at protein level). Not detected in normal intestinal epithelium (at protein level). Expressed in brain cortex; expression is significantly increased in the front cortex of Alzheimer disease patients.
• Reactome Pathway: Post-translational modification (R-HSA-163125)

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 increases the methylation of Prostate stem cell antigen (PSCA).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Prostate stem cell antigen (PSCA).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Prostate stem cell antigen (PSCA).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Prostate stem cell antigen (PSCA).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Prostate stem cell antigen (PSCA).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Prostate stem cell antigen (PSCA).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Prostate stem cell antigen (PSCA).	[7]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of Prostate stem cell antigen (PSCA).	[8]
ACYLINE	DM9GRTK	Phase 2	ACYLINE decreases the expression of Prostate stem cell antigen (PSCA).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Prostate stem cell antigen (PSCA).	[10]
Flavonoid derivative 1	DMCQP0B	Patented	Flavonoid derivative 1 decreases the expression of Prostate stem cell antigen (PSCA).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Prostate stem cell antigen (PSCA).	[11]
Chrysin	DM7V2LG	Investigative	Chrysin decreases the expression of Prostate stem cell antigen (PSCA).	[6]
Kaempferol	DMHEMUB	Investigative	Kaempferol decreases the expression of Prostate stem cell antigen (PSCA).	[6]
Apigenin	DMI3491	Investigative	Apigenin decreases the expression of Prostate stem cell antigen (PSCA).	[6]
Myricetin	DMTV4L0	Investigative	Myricetin decreases the expression of Prostate stem cell antigen (PSCA).	[6]

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] 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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [6] Flavones and flavonols exert cytotoxic effects on a human oesophageal adenocarcinoma cell line (OE33) by causing G2/M arrest and inducing apoptosis. Food Chem Toxicol. 2008 Jun;46(6):2042-53. doi: 10.1016/j.fct.2008.01.049. Epub 2008 Feb 7.
• [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] 2,3,7,8-tetrachlorodibenzo-p-dioxin augments the modulation of gene expression mediated by the thyroid hormone receptor. Toxicol Appl Pharmacol. 2004 Feb 1;194(3):201-10. doi: 10.1016/j.taap.2003.09.010.
• [9] Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res. 2007 May 15;67(10):5033-41.
• [10] Effect of benzo[a]pyrene on proliferation and metastasis of oral squamous cell carcinoma cells: A transcriptome analysis based on RNA-seq. Environ Toxicol. 2022 Nov;37(11):2589-2604. doi: 10.1002/tox.23621. Epub 2022 Jul 23.
• [11] Editor's Highlight: Transcriptome Profiling Reveals Bisphenol A Alternatives Activate Estrogen Receptor Alpha in Human Breast Cancer Cells. Toxicol Sci. 2017 Aug 1;158(2):431-443. doi: 10.1093/toxsci/kfx101.