Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB19LEQ)

DOT Name	Protein odd-skipped-related 1 (OSR1)
Gene Name	OSR1
Related Disease	Carcinoma of esophagus ( ) Esophageal cancer ( ) Generalized anxiety disorder ( ) Neoplasm of esophagus ( ) Advanced cancer ( ) Alagille syndrome ( ) Anxiety disorder ( ) Bone cancer ( ) Bone osteosarcoma ( ) Clear cell renal carcinoma ( ) Conduct disorder ( ) Cowden disease ( ) Depression ( ) Disruptive behavior disorder ( ) Gastric cancer ( ) High blood pressure ( ) Huntington disease ( ) Lung adenocarcinoma ( ) Lung cancer ( ) Lung carcinoma ( ) Mental disorder ( ) Mitochondrial DNA depletion syndrome 4a ( ) Mood disorder ( ) Polycystic kidney disease ( ) Prostate neoplasm ( ) Renal cell carcinoma ( ) Stomach cancer ( ) Vesicoureteral reflux ( ) Gordon syndrome ( ) Hepatocellular carcinoma ( ) Hyperinsulinemia ( ) Squamous cell carcinoma ( ) Aortic aneurysm ( ) Melanoma ( ) Non-small-cell lung cancer ( ) Anxiety ( ) Atrial septal defect ( ) Childhood kidney Wilms tumor ( ) Neoplasm ( ) Prostate cancer ( ) Prostate carcinoma ( ) Wilms tumor ( )
UniProt ID	OSR1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF00096
Sequence	MGSKTLPAPVPIHPSLQLTNYSFLQAVNGLPTVPSDHLPNLYGFSALHAVHLHQWTLGYP AMHLPRSSFSKVPGTVSSLVDARFQLPAFPWFPHVIQPKPEITAGGSVPALKTKPRFDFA NLALAATQEDPAKLGRGEGPGSPAGGLGALLDVTKLSPEKKPTRGRLPSKTKKEFVCKFC GRHFTKSYNLLIHERTHTDERPYTCDICHKAFRRQDHLRDHRYIHSKEKPFKCQECGKGF CQSRTLAVHKTLHSQVKELKTSKIKC
Function	Transcription factor that plays a role in the regulation of embryonic heart and urogenital development.
Tissue Specificity	Expressed in adult colon, small intestine, prostate, testis, and fetal lung.
Reactome Pathway	Formation of intermediate mesoderm (R-HSA-9761174 )

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Carcinoma of esophagus	DISS6G4D	Definitive	Altered Expression	[1]
Esophageal cancer	DISGB2VN	Definitive	Altered Expression	[1]
Generalized anxiety disorder	DISPSQCW	Definitive	Biomarker	[2]
Neoplasm of esophagus	DISOLKAQ	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alagille syndrome	DIS9DPU8	Strong	Biomarker	[4]
Anxiety disorder	DISBI2BT	Strong	Genetic Variation	[5]
Bone cancer	DIS38NA0	Strong	Biomarker	[6]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[6]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[7]
Conduct disorder	DISOLUZ1	Strong	Biomarker	[8]
Cowden disease	DISMYKCE	Strong	Biomarker	[8]
Depression	DIS3XJ69	Strong	Biomarker	[9]
Disruptive behavior disorder	DIS5ACCI	Strong	Biomarker	[10]
Gastric cancer	DISXGOUK	Strong	Biomarker	[11]
High blood pressure	DISY2OHH	Strong	Biomarker	[12]
Huntington disease	DISQPLA4	Strong	Altered Expression	[13]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[14]
Lung cancer	DISCM4YA	Strong	Altered Expression	[15]
Lung carcinoma	DISTR26C	Strong	Biomarker	[15]
Mental disorder	DIS3J5R8	Strong	Biomarker	[16]
Mitochondrial DNA depletion syndrome 4a	DISU4RVU	Strong	Biomarker	[4]
Mood disorder	DISLVMWO	Strong	Biomarker	[2]
Polycystic kidney disease	DISWS3UY	Strong	Biomarker	[12]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[17]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[7]
Stomach cancer	DISKIJSX	Strong	Biomarker	[11]
Vesicoureteral reflux	DISUL6SA	Strong	Biomarker	[18]
Gordon syndrome	DISVMP0Y	moderate	Biomarker	[19]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[20]
Hyperinsulinemia	DISIDWT6	moderate	Biomarker	[21]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[22]
Aortic aneurysm	DISQ5KRA	Disputed	Biomarker	[23]
Melanoma	DIS1RRCY	Disputed	Biomarker	[23]
Non-small-cell lung cancer	DIS5Y6R9	Disputed	Biomarker	[23]
Anxiety	DISIJDBA	Limited	Genetic Variation	[5]
Atrial septal defect	DISJT76B	Limited	Biomarker	[24]
Childhood kidney Wilms tumor	DIS0NMK3	Limited	Altered Expression	[25]
Neoplasm	DISZKGEW	Limited	Biomarker	[23]
Prostate cancer	DISF190Y	Limited	Genetic Variation	[26]
Prostate carcinoma	DISMJPLE	Limited	Genetic Variation	[26]
Wilms tumor	DISB6T16	Limited	Altered Expression	[25]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein odd-skipped-related 1 (OSR1).	[27]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein odd-skipped-related 1 (OSR1).	[29]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Protein odd-skipped-related 1 (OSR1).	[30]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Protein odd-skipped-related 1 (OSR1).	[31]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Protein odd-skipped-related 1 (OSR1).	[32]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Protein odd-skipped-related 1 (OSR1).	[33]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein odd-skipped-related 1 (OSR1).	[34]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein odd-skipped-related 1 (OSR1).	[36]
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⏷ Show the Full List of 8 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Protein odd-skipped-related 1 (OSR1).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein odd-skipped-related 1 (OSR1).	[35]
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References

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2	External validation of a bifactor model of oppositional defiant disorder.Mol Psychiatry. 2021 Feb;26(2):682-693. doi: 10.1038/s41380-018-0294-z. Epub 2018 Dec 11.
3	Ascorbic acid metabolism and functions: A comparison of plants and mammals.Free Radic Biol Med. 2018 Jul;122:116-129. doi: 10.1016/j.freeradbiomed.2018.03.033. Epub 2018 Mar 20.
4	Child and adolescent traumatic brain injury: correlates of disruptive behaviour disorders.Brain Inj. 1998 Jan;12(1):41-52. doi: 10.1080/026990598122845.
5	Examining the relationships between error-related brain activity (the ERN) and anxiety disorders versus externalizing disorders in young children: Focusing on cognitive control, fear, and shyness.Compr Psychiatry. 2018 Nov;87:112-119. doi: 10.1016/j.comppsych.2018.09.009. Epub 2018 Oct 7.
6	Suppression of WNK1-SPAK/OSR1 Attenuates Bone Cancer Pain by Regulating NKCC1 and KCC2.J Pain. 2019 Dec;20(12):1416-1428. doi: 10.1016/j.jpain.2019.05.005. Epub 2019 May 11.
7	Odd-skipped related transcription factor 1 (OSR1) suppresses tongue squamous cell carcinoma migration and invasion through inhibiting NF-B pathway.Eur J Pharmacol. 2018 Nov 15;839:33-39. doi: 10.1016/j.ejphar.2018.09.020. Epub 2018 Sep 19.
8	The role of effortful control in the development of ADHD, ODD, and CD symptoms.J Pers Soc Psychol. 2020 Jun;118(6):1226-1246. doi: 10.1037/pspp0000243. Epub 2019 Mar 28.
9	Genetic Overlap Between Schizophrenia and Developmental Psychopathology: Longitudinal and Multivariate Polygenic Risk Prediction of Common Psychiatric Traits During Development.Schizophr Bull. 2017 Oct 21;43(6):1197-1207. doi: 10.1093/schbul/sbx031.
10	Oppositional Defiant Disorder Is Better Conceptualized as a Disorder of Emotional Regulation.J Atten Disord. 2017 Mar;21(5):381-389. doi: 10.1177/1087054713520221. Epub 2016 Jul 28.
11	Odd-skipped related 1 is a novel tumour suppressor gene and a potential prognostic biomarker in gastric cancer.J Pathol. 2014 Nov;234(3):302-15. doi: 10.1002/path.4391. Epub 2014 Aug 28.
12	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.
13	Transcriptomics of maternal and fetal membranes can discriminate between gestational-age matched preterm neonates with and without cognitive impairment diagnosed at 18-24 months.PLoS One. 2015 Mar 30;10(3):e0118573. doi: 10.1371/journal.pone.0118573. eCollection 2015.
14	Identification and validation of candidate epigenetic biomarkers in lung adenocarcinoma.Sci Rep. 2016 Oct 26;6:35807. doi: 10.1038/srep35807.
15	Odd-skipped related 1 inhibits lung cancer proliferation and invasion by reducing Wnt signaling through the suppression of SOX9 and -catenin.Cancer Sci. 2018 Jun;109(6):1799-1810. doi: 10.1111/cas.13614. Epub 2018 May 23.
16	Do Individual Differences in Early Affective and Cognitive Self-Regulation Predict Developmental Change in ADHD Symptoms From Preschool to Adolescence?.J Atten Disord. 2017 Feb 1;23(13):1656-1666. doi: 10.1177/1087054717693372. Print 2019 Nov 1.
17	Conditional expression of the androgen receptor induces oncogenic transformation of the mouse prostate.J Biol Chem. 2011 Sep 23;286(38):33478-88. doi: 10.1074/jbc.M111.269894. Epub 2011 Jul 27.
18	Heterozygous loss-of-function mutation in Odd-skipped related 1 (Osr1) is associated with vesicoureteric reflux, duplex systems, and hydronephrosis.Am J Physiol Renal Physiol. 2017 Nov 1;313(5):F1106-F1115. doi: 10.1152/ajprenal.00107.2017. Epub 2017 Jul 19.
19	Functional interactions of the SPAK/OSR1 kinases with their upstream activator WNK1 and downstream substrate NKCC1.Biochem J. 2006 Jul 1;397(1):223-31. doi: 10.1042/BJ20060220.
20	Discovery of NKCC1 as a potential therapeutic target to inhibit hepatocellular carcinoma cell growth and metastasis.Oncotarget. 2017 Aug 12;8(39):66328-66342. doi: 10.18632/oncotarget.20240. eCollection 2017 Sep 12.
21	Regulation of with-no-lysine kinase signaling by Kelch-like proteins.Biol Cell. 2014 Feb;106(2):45-56. doi: 10.1111/boc.201300069. Epub 2014 Jan 10.
22	DNA methylation biomarkers for lung cancer.Tumour Biol. 2012 Apr;33(2):287-96. doi: 10.1007/s13277-011-0282-2. Epub 2011 Dec 6.
23	Trial watch: Peptide-based vaccines in anticancer therapy.Oncoimmunology. 2018 Sep 6;7(12):e1511506. doi: 10.1080/2162402X.2018.1511506. eCollection 2018.
24	Testing the specificity of executive functioning impairments in adolescents with ADHD, ODD/CD and ASD.Eur Child Adolesc Psychiatry. 2018 Jul;27(7):899-908. doi: 10.1007/s00787-017-1089-5. Epub 2017 Dec 9.
25	Clear cell sarcoma of the kidney demonstrates an embryonic signature indicative of a primitive nephrogenic origin.Genes Chromosomes Cancer. 2014 May;53(5):381-91. doi: 10.1002/gcc.22149. Epub 2014 Feb 1.
26	Combining Optical Reporter Proteins with Different Half-lives to Detect Temporal Evolution of Hypoxia and Reoxygenation in Tumors.Neoplasia. 2015 Dec;17(12):871-881. doi: 10.1016/j.neo.2015.11.007.
27	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.
28	Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
29	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.
30	Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
31	Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
32	Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
33	Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
34	Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
35	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.
36	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.