Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN8C6JQ)

• DOT Name: Oxidative stress-responsive serine-rich protein 1 (OSER1)
• Synonyms: Oxidative stress-responsive protein 1; Peroxide-inducible transcript 1 protein
• Gene Name: OSER1
• Related Disease:
  High blood pressure
  Polycystic kidney disease
• UniProt ID: OSER1_HUMAN
• Pfam ID: PF05604
• Sequence:
  MKSEAKDGEEESLQTAFKKLRVDASGSVASLSVGEGTGVRAPVRTATDDTKPKTTCASKD
  SWHGSTRKSSRGAVRTQRRRRSKSPVLHPPKFIHCSTIASSSSSQLKHKSQTDSPDGSSG
  LGISSPKEFSAGESSTSLDANHTGAVVEPLRTSVPRLPSESKKEDSSDATQVPQASLKAS
  DLSDFQSVSKLNQGKPCTCIGKECQCKRWHDMEVYSFSGLQSVPPLAPERRSTLEDYSQS
  LHARTLSGSPRSCSEQARVFVDDVTIEDLSGYMEYYLYIPKKMSHMAEMMYT

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
High blood pressure	DISY2OHH	Strong	Biomarker	[1]
Polycystic kidney disease	DISWS3UY	Strong	Biomarker	[1]

16 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 Oxidative stress-responsive serine-rich protein 1 (OSER1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Oxidative stress-responsive serine-rich protein 1 (OSER1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Oxidative stress-responsive serine-rich protein 1 (OSER1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Oxidative stress-responsive serine-rich protein 1 (OSER1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Oxidative stress-responsive serine-rich protein 1 (OSER1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Oxidative stress-responsive serine-rich protein 1 (OSER1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Oxidative stress-responsive serine-rich protein 1 (OSER1).	[8]
Marinol	DM70IK5	Approved	Marinol increases the expression of Oxidative stress-responsive serine-rich protein 1 (OSER1).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Oxidative stress-responsive serine-rich protein 1 (OSER1).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Oxidative stress-responsive serine-rich protein 1 (OSER1).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Oxidative stress-responsive serine-rich protein 1 (OSER1).	[13]
Celastrol	DMWQIJX	Preclinical	Celastrol increases the expression of Oxidative stress-responsive serine-rich protein 1 (OSER1).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Oxidative stress-responsive serine-rich protein 1 (OSER1).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Oxidative stress-responsive serine-rich protein 1 (OSER1).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Oxidative stress-responsive serine-rich protein 1 (OSER1).	[18]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Oxidative stress-responsive serine-rich protein 1 (OSER1).	[19]

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 Oxidative stress-responsive serine-rich protein 1 (OSER1).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Oxidative stress-responsive serine-rich protein 1 (OSER1).	[14]

References

• [1] Association of OSR-1 With Vascular Dysfunction and Hypertension in Polycystic Kidney Disease.Ther Apher Dial. 2020 Feb;24(1):64-71. doi: 10.1111/1744-9987.12814. Epub 2019 Jul 4.
• [2] 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.
• [3] 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.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [9] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [10] 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.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] 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.
• [15] Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer Cell. 2006 Oct;10(4):321-30.
• [16] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [18] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [19] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.