Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJMW5R9)

• DOT Name: STEAP1 protein (STEAP1)
• Synonyms: Six-transmembrane epithelial antigen of prostate 1
• Gene Name: STEAP1
• UniProt ID: STEA1_HUMAN
• PDB ID: 6Y9B; 8UCD
• Pfam ID: PF01794
• Sequence:
  MESRKDITNQEELWKMKPRRNLEEDDYLHKDTGETSMLKRPVLLHLHQTAHADEFDCPSE
  LQHTQELFPQWHLPIKIAAIIASLTFLYTLLREVIHPLATSHQQYFYKIPILVINKVLPM
  VSITLLALVYLPGVIAAIVQLHNGTKYKKFPHWLDKWMLTRKQFGLLSFFFAVLHAIYSL
  SYPMRRSYRYKLLNWAYQQVQQNKEDAWIEHDVWRMEIYVSLGIVGLAILALLAVTSIPS
  VSDSLTWREFHYIQSKLGIVSLLLGTIHALIFAWNKWIDIKQFVWYTPPTFMIAVFLPIV
  VLIFKSILFLPCLRKKILKIRHGWEDVTKINKTEICSQL
• Function: Does not function as a metalloreductase due to the absence of binding sites for the electron-donating substrate NADPH. Promotes Fe(3+) reduction when fused to the NADPH-binding domain of STEAP4.
• Tissue Specificity: Ubiquitously expressed. Highly expressed in prostate tumors.
• KEGG Pathway: Mineral absorption (hsa04978)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	STEAP1 protein (STEAP1) affects the response to substance of Cisplatin.	[21]

21 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 STEAP1 protein (STEAP1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of STEAP1 protein (STEAP1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of STEAP1 protein (STEAP1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of STEAP1 protein (STEAP1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of STEAP1 protein (STEAP1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of STEAP1 protein (STEAP1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of STEAP1 protein (STEAP1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of STEAP1 protein (STEAP1).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of STEAP1 protein (STEAP1).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of STEAP1 protein (STEAP1).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of STEAP1 protein (STEAP1).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of STEAP1 protein (STEAP1).	[12]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of STEAP1 protein (STEAP1).	[13]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of STEAP1 protein (STEAP1).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of STEAP1 protein (STEAP1).	[10]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of STEAP1 protein (STEAP1).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of STEAP1 protein (STEAP1).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of STEAP1 protein (STEAP1).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of STEAP1 protein (STEAP1).	[18]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of STEAP1 protein (STEAP1).	[19]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of STEAP1 protein (STEAP1).	[20]

2 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 STEAP1 protein (STEAP1).	[15]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of STEAP1 protein (STEAP1).	[17]

References

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• [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.
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• [7] Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
• [8] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] 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.
• [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] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [13] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [14] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [15] 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.
• [16] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [17] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [18] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [19] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [20] Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.
• [21] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.