Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3TFQ0U)

• DOT Name: Homeobox protein Hox-B6 (HOXB6)
• Synonyms: Homeobox protein Hox-2.2; Homeobox protein Hox-2B; Homeobox protein Hu-2
• Gene Name: HOXB6
• Related Disease:
  Acute lymphocytic leukaemia
  Adult glioblastoma
  Barrett esophagus
  Campomelic dysplasia
  Colorectal carcinoma
  Glioblastoma multiforme
  Hypospadias
  leukaemia
  Leukemia
  Neuroblastoma
  Pancreatic cancer
  Renal carcinoma
  Renal cell carcinoma
  Rhabdomyosarcoma
  Acute myelogenous leukaemia
• UniProt ID: HXB6_HUMAN
• Pfam ID: PF00046
• Sequence:
  MSSYFVNSTFPVTLASGQESFLGQLPLYSSGYADPLRHYPAPYGPGPGQDKGFATSSYYP
  PAGGGYGRAAPCDYGPAPAFYREKESACALSGADEQPPFHPEPRKSDCAQDKSVFGETEE
  QKCSTPVYPWMQRMNSCNSSSFGPSGRRGRQTYTRYQTLELEKEFHYNRYLTRRRRIEIA
  HALCLTERQIKIWFQNRRMKWKKESKLLSASQLSAEEEEEKQAE
• Function: Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[1]
Adult glioblastoma	DISVP4LU	Strong	Genetic Variation	[2]
Barrett esophagus	DIS416Y7	Strong	Altered Expression	[3]
Campomelic dysplasia	DISVTW53	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Glioblastoma multiforme	DISK8246	Strong	Genetic Variation	[2]
Hypospadias	DIS48CCP	Strong	Genetic Variation	[6]
leukaemia	DISS7D1V	Strong	Altered Expression	[1]
Leukemia	DISNAKFL	Strong	Altered Expression	[1]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[2]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[7]
Renal carcinoma	DISER9XT	Strong	Genetic Variation	[8]
Renal cell carcinoma	DISQZ2X8	Strong	Genetic Variation	[8]
Rhabdomyosarcoma	DISNR7MS	moderate	Biomarker	[9]
Acute myelogenous leukaemia	DISCSPTN	Limited	Altered Expression	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Homeobox protein Hox-B6 (HOXB6).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Homeobox protein Hox-B6 (HOXB6).	[12]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Homeobox protein Hox-B6 (HOXB6).	[13]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Homeobox protein Hox-B6 (HOXB6).	[14]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Homeobox protein Hox-B6 (HOXB6).	[15]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Homeobox protein Hox-B6 (HOXB6).	[16]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Homeobox protein Hox-B6 (HOXB6).	[17]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Homeobox protein Hox-B6 (HOXB6).	[18]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Homeobox protein Hox-B6 (HOXB6).	[19]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Homeobox protein Hox-B6 (HOXB6).	[20]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Homeobox protein Hox-B6 (HOXB6).	[21]

References

• [1] Expression of selected human HOX-2 genes in B/T acute lymphoid leukemia and interleukin-2/interleukin-1 beta-stimulated natural killer lymphocytes.Blood. 1992 Jul 1;80(1):185-93.
• [2] Modulation of HOX2 gene expression following differentiation of neuronal cell lines.Differentiation. 1992 Sep;51(1):39-47. doi: 10.1111/j.1432-0436.1992.tb00678.x.
• [3] Evidence for a functional role of epigenetically regulated midcluster HOXB genes in the development of Barrett esophagus.Proc Natl Acad Sci U S A. 2012 Jun 5;109(23):9077-82. doi: 10.1073/pnas.1116933109. Epub 2012 May 17.
• [4] Assignment of an autosomal sex reversal locus (SRA1) and campomelic dysplasia (CMPD1) to 17q24.3-q25.1.Nat Genet. 1993 Jun;4(2):170-4. doi: 10.1038/ng0693-170.
• [5] Deregulated expression of homeobox-containing genes, HOXB6, B8, C8, C9, and Cdx-1, in human colon cancer cell lines.Biochem Biophys Res Commun. 2000 Jun 7;272(2):513-8. doi: 10.1006/bbrc.2000.2804.
• [6] Mutation screening of BMP4, BMP7, HOXA4 and HOXB6 genes in Chinese patients with hypospadias.Eur J Hum Genet. 2007 Jan;15(1):23-8. doi: 10.1038/sj.ejhg.5201722. Epub 2006 Sep 27.
• [7] Expression of HOXB2, a retinoic acid signaling target in pancreatic cancer and pancreatic intraepithelial neoplasia.Clin Cancer Res. 2005 May 1;11(9):3587-96. doi: 10.1158/1078-0432.CCR-04-1813.
• [8] HOX gene expression in normal and neoplastic human kidney.Int J Cancer. 1992 Jul 30;51(6):892-7. doi: 10.1002/ijc.2910510610.
• [9] Identification and pharmacological characterization of native, functional human urotensin-II receptors in rhabdomyosarcoma cell lines.Br J Pharmacol. 2004 Jul;142(6):921-32. doi: 10.1038/sj.bjp.0705743. Epub 2004 Jun 21.
• [10] Expression pattern of HOXB6 homeobox gene in myelomonocytic differentiation and acute myeloid leukemia.Leukemia. 2002 Jul;16(7):1293-301. doi: 10.1038/sj.leu.2402532.
• [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] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [13] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [14] Quercetin induced cell apoptosis and altered gene expression in AGS human gastric cancer cells. Environ Toxicol. 2018 Nov;33(11):1168-1181. doi: 10.1002/tox.22623. Epub 2018 Aug 27.
• [15] 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.
• [16] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [17] 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.
• [18] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [19] Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
• [20] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [21] 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.