Details of Drug Off-Target (DOT)

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

• DOT Name: Intestine-specific homeobox (ISX)
• Synonyms: RAX-like homeobox
• Gene Name: ISX
• Related Disease:
  Crohn disease
  Neoplasm
  Colorectal carcinoma
  Hepatocellular carcinoma
  Schizophrenia
  Advanced cancer
  Gastric cancer
  Stomach cancer
• UniProt ID: ISX_HUMAN
• Pfam ID: PF00046
• Sequence:
  MCAEVGPALCRGMERNSLGCCEAPKKLSLSFSIEAILKRPARRSDMDRPEGPGEEGPGEA
  AASGSGLEKPPKDQPQEGRKSKRRVRTTFTTEQLHELEKIFHFTHYPDVHIRSQLAARIN
  LPEARVQIWFQNQRAKWRKQEKIGNLGAPQQLSEASVALPTNLDVAGPTWTSTALRRLAP
  PTSCCPSAQDQLASAWFPAWITLLPAHPWETQPVPGLPIHQTCIPVLCILPPPHPKWGSI
  CATST
• Function: Transcription factor that regulates gene expression in intestine. May participate in vitamin A metabolism most likely by regulating BCO1 expression in the intestine.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Crohn disease	DIS2C5Q8	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[4]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[5]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[6]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[6]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[6]

8 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 Intestine-specific homeobox (ISX).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Intestine-specific homeobox (ISX).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Intestine-specific homeobox (ISX).	[9]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Intestine-specific homeobox (ISX).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Intestine-specific homeobox (ISX).	[10]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Intestine-specific homeobox (ISX).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Intestine-specific homeobox (ISX).	[12]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE increases the expression of Intestine-specific homeobox (ISX).	[8]

References

• [1] SNP-SNP interactions discovered by logic regression explain Crohn's disease genetics.PLoS One. 2012;7(10):e43035. doi: 10.1371/journal.pone.0043035. Epub 2012 Oct 12.
• [2] Proinflammatory homeobox gene, ISX, regulates tumor growth and survival in hepatocellular carcinoma.Cancer Res. 2013 Jan 15;73(2):508-18. doi: 10.1158/0008-5472.CAN-12-2795. Epub 2012 Dec 5.
• [3] Novel chemosensitive single-nucleotide polymorphism markers to targeted regimens in metastatic colorectal cancer. Clin Cancer Res. 2011 Mar 1;17(5):1200-9.
• [4] Aryl hydrocarbon receptor promotes hepatocellular carcinoma tumorigenesis by targeting intestine-specific homeobox expression.Mol Carcinog. 2017 Oct;56(10):2167-2177. doi: 10.1002/mc.22658. Epub 2017 Jul 28.
• [5] Genome-wide association study with the risk of schizophrenia in a Korean population.Am J Med Genet B Neuropsychiatr Genet. 2016 Mar;171B(2):257-65. doi: 10.1002/ajmg.b.32400. Epub 2015 Nov 4.
• [6] Intestine-specific homeobox (ISX) induces intestinal metaplasia and cell proliferation to contribute to gastric carcinogenesis.J Gastroenterol. 2016 Oct;51(10):949-60. doi: 10.1007/s00535-016-1176-2. Epub 2016 Feb 12.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [12] 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.