Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6DQAM1)

• DOT Name: Serine protease 23 (PRSS23)
• Synonyms: EC 3.4.21.-; Putative secreted protein Zsig13
• Gene Name: PRSS23
• Related Disease:
  Acute myocardial infarction
  Advanced cancer
  Exudative vitreoretinopathy
  Gastric cancer
  Melanoma
  Myocardial ischemia
  Neoplasm
  Stomach cancer
  Breast cancer
  Breast carcinoma
• UniProt ID: PRS23_HUMAN
• EC Number: 3.4.21.-
• Pfam ID: PF00089
• Sequence:
  MAGIPGLLFLLFFLLCAVGQVSPYSAPWKPTWPAYRLPVVLPQSTLNLAKPDFGAEAKLE
  VSSSCGPQCHKGTPLPTYEEAKQYLSYETLYANGSRTETQVGIYILSSSGDGAQHRDSGS
  SGKSRRKRQIYGYDSRFSIFGKDFLLNYPFSTSVKLSTGCTGTLVAEKHVLTAAHCIHDG
  KTYVKGTQKLRVGFLKPKFKDGGRGANDSTSAMPEQMKFQWIRVKRTHVPKGWIKGNAND
  IGMDYDYALLELKKPHKRKFMKIGVSPPAKQLPGGRIHFSGYDNDRPGNLVYRFCDVKDE
  TYDLLYQQCDAQPGASGSGVYVRMWKRQQQKWERKIIGIFSGHQWVDMNGSPQDFNVAVR
  ITPLKYAQICYWIKGNYLDCREG
• Reactome Pathway:
  Post-translational protein phosphorylation (R-HSA-8957275)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Exudative vitreoretinopathy	DISWN0TG	Strong	CausalMutation	[3]
Gastric cancer	DISXGOUK	Strong	Biomarker	[2]
Melanoma	DIS1RRCY	Strong	Biomarker	[4]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Stomach cancer	DISKIJSX	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	moderate	Biomarker	[5]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Serine protease 23 (PRSS23).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Serine protease 23 (PRSS23).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serine protease 23 (PRSS23).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Serine protease 23 (PRSS23).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Serine protease 23 (PRSS23).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Serine protease 23 (PRSS23).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Serine protease 23 (PRSS23).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Serine protease 23 (PRSS23).	[13]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Serine protease 23 (PRSS23).	[12]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Serine protease 23 (PRSS23).	[14]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Serine protease 23 (PRSS23).	[15]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Serine protease 23 (PRSS23).	[16]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Serine protease 23 (PRSS23).	[17]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Serine protease 23 (PRSS23).	[18]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Serine protease 23 (PRSS23).	[19]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Serine protease 23 (PRSS23).	[13]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Serine protease 23 (PRSS23).	[21]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Serine protease 23 (PRSS23).	[22]
Palbociclib	DMD7L94	Approved	Palbociclib increases the expression of Serine protease 23 (PRSS23).	[23]
Estrone	DM5T6US	Approved	Estrone increases the expression of Serine protease 23 (PRSS23).	[21]
Mestranol	DMG3F94	Approved	Mestranol increases the expression of Serine protease 23 (PRSS23).	[21]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Serine protease 23 (PRSS23).	[13]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Serine protease 23 (PRSS23).	[11]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Serine protease 23 (PRSS23).	[24]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Serine protease 23 (PRSS23).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Serine protease 23 (PRSS23).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Serine protease 23 (PRSS23).	[25]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Serine protease 23 (PRSS23).	[26]
HEXESTROL	DM9AGWQ	Withdrawn from market	HEXESTROL increases the expression of Serine protease 23 (PRSS23).	[21]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Serine protease 23 (PRSS23).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Serine protease 23 (PRSS23).	[28]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Serine protease 23 (PRSS23).	[29]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Serine protease 23 (PRSS23).	[30]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Serine protease 23 (PRSS23).	[11]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Serine protease 23 (PRSS23).	[31]
Daidzein	DMRFTJX	Investigative	Daidzein increases the expression of Serine protease 23 (PRSS23).	[28]
HPTE	DMRPZD4	Investigative	HPTE increases the expression of Serine protease 23 (PRSS23).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Serine protease 23 (PRSS23).	[20]

References

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• [2] PRSS23 knockdown inhibits gastric tumorigenesis through EIF2 signaling.Pharmacol Res. 2019 Apr;142:50-57. doi: 10.1016/j.phrs.2019.02.008. Epub 2019 Feb 12.
• [3] Mutation spectrum of the FZD-4, TSPAN12 AND ZNF408 genes in Indian FEVR patients. BMC Ophthalmol. 2016 Jun 17;16:90. doi: 10.1186/s12886-016-0236-y.
• [4] Aggressiveness of human melanoma xenograft models is promoted by aneuploidy-driven gene expression deregulation.Oncotarget. 2012 Apr;3(4):399-413. doi: 10.18632/oncotarget.473.
• [5] Serine protease PRSS23 is upregulated by estrogen receptor and associated with proliferation of breast cancer cells.PLoS One. 2012;7(1):e30397. doi: 10.1371/journal.pone.0030397. Epub 2012 Jan 23.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] 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.
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• [9] 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.
• [10] 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.
• [11] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [12] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [13] 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.
• [14] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [15] 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.
• [16] 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.
• [17] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [18] 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.
• [19] Progesterone rise on HCG day in GnRH antagonist/rFSH stimulated cycles affects endometrial gene expression. Reprod Biomed Online. 2011 Mar;22(3):263-71. doi: 10.1016/j.rbmo.2010.11.002. Epub 2010 Nov 13.
• [20] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [21] Moving toward integrating gene expression profiling into high-throughput testing: a gene expression biomarker accurately predicts estrogen receptor alpha modulation in a microarray compendium. Toxicol Sci. 2016 May;151(1):88-103.
• [22] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [23] Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells. Mol Cancer Ther. 2012 Oct;11(10):2138-48. doi: 10.1158/1535-7163.MCT-12-0562. Epub 2012 Aug 6.
• [24] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [25] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [26] 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.
• [27] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [28] Endocrine-Disrupting Chemicals (EDCs): In Vitro Mechanism of Estrogenic Activation and Differential Effects on ER Target Genes. Environ Health Perspect. 2013 Apr;121(4):459-66. doi: 10.1289/ehp.1205951. Epub 2013 Feb 5.
• [29] 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.
• [30] 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.
• [31] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.