Details of Drug Off-Target (DOT)

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

DOT Name Homeobox protein CDX-1 (CDX1)
Synonyms Caudal-type homeobox protein 1
Gene Name CDX1
Related Disease
Carcinoma ( )
Cervical cancer ( )
Cervical carcinoma ( )
Cholangiocarcinoma ( )
Colon adenocarcinoma ( )
Colonic neoplasm ( )
Colorectal carcinoma ( )
Colorectal neoplasm ( )
Endometriosis ( )
Gastritis ( )
Gastroesophageal reflux disease ( )
Head-neck squamous cell carcinoma ( )
Hepatitis B virus infection ( )
Hepatocellular carcinoma ( )
Pancreatic cancer ( )
Polyp ( )
Precancerous condition ( )
Retinoblastoma ( )
Enterocolitis ( )
Hirschsprung disease ( )
Stomach cancer ( )
Adenocarcinoma ( )
Advanced cancer ( )
Colon cancer ( )
Colon carcinoma ( )
Gastric cancer ( )
Wilms tumor ( )
UniProt ID
CDX1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
5LUX; 7Q3O
Pfam ID
PF04731 ; PF00046
Sequence
MYVGYVLDKDSPVYPGPARPASLGLGPQAYGPPAPPPAPPQYPDFSSYSHVEPAPAPPTA
WGAPFPAPKDDWAAAYGPGPAAPAASPASLAFGPPPDFSPVPAPPGPGPGLLAQPLGGPG
TPSSPGAQRPTPYEWMRRSVAAGGGGGSGKTRTKDKYRVVYTDHQRLELEKEFHYSRYIT
IRRKSELAANLGLTERQVKIWFQNRRAKERKVNKKKQQQQQPPQPPMAHDITATPAGPSL
GGLCPSNTSLLATSSPMPVKEEFLP
Function
Plays a role in transcriptional regulation. Involved in activated KRAS-mediated transcriptional activation of PRKD1 in colorectal cancer (CRC) cells. Binds to the PRKD1 promoter in colorectal cancer (CRC) cells. Could play a role in the terminal differentiation of the intestine. Binds preferentially to methylated DNA.
Tissue Specificity Intestinal epithelium.

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Carcinoma DISH9F1N Strong Altered Expression [1]
Cervical cancer DISFSHPF Strong Biomarker [2]
Cervical carcinoma DIST4S00 Strong Biomarker [2]
Cholangiocarcinoma DIS71F6X Strong Altered Expression [3]
Colon adenocarcinoma DISDRE0J Strong Biomarker [4]
Colonic neoplasm DISSZ04P Strong Posttranslational Modification [5]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [6]
Colorectal neoplasm DISR1UCN Strong Altered Expression [7]
Endometriosis DISX1AG8 Strong Altered Expression [8]
Gastritis DIS8G07K Strong Altered Expression [9]
Gastroesophageal reflux disease DISQ8G5S Strong Biomarker [10]
Head-neck squamous cell carcinoma DISF7P24 Strong Altered Expression [3]
Hepatitis B virus infection DISLQ2XY Strong Altered Expression [11]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [11]
Pancreatic cancer DISJC981 Strong Altered Expression [12]
Polyp DISRSLYF Strong Genetic Variation [7]
Precancerous condition DISV06FL Strong Altered Expression [13]
Retinoblastoma DISVPNPB Strong Altered Expression [14]
Enterocolitis DISYACTL moderate Altered Expression [15]
Hirschsprung disease DISUUSM1 moderate Altered Expression [15]
Stomach cancer DISKIJSX moderate Biomarker [16]
Adenocarcinoma DIS3IHTY Limited Altered Expression [17]
Advanced cancer DISAT1Z9 Limited Biomarker [18]
Colon cancer DISVC52G Limited Biomarker [19]
Colon carcinoma DISJYKUO Limited Biomarker [19]
Gastric cancer DISXGOUK Limited Biomarker [16]
Wilms tumor DISB6T16 Limited Biomarker [20]
------------------------------------------------------------------------------------
⏷ Show the Full List of 27 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Homeobox protein CDX-1 (CDX1). [21]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Homeobox protein CDX-1 (CDX1). [28]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Homeobox protein CDX-1 (CDX1). [31]
------------------------------------------------------------------------------------
8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Homeobox protein CDX-1 (CDX1). [22]
Triclosan DMZUR4N Approved Triclosan increases the expression of Homeobox protein CDX-1 (CDX1). [23]
Decitabine DMQL8XJ Approved Decitabine increases the expression of Homeobox protein CDX-1 (CDX1). [24]
Marinol DM70IK5 Approved Marinol decreases the expression of Homeobox protein CDX-1 (CDX1). [25]
Folic acid DMEMBJC Approved Folic acid increases the expression of Homeobox protein CDX-1 (CDX1). [26]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of Homeobox protein CDX-1 (CDX1). [27]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Homeobox protein CDX-1 (CDX1). [29]
CHIR-99021 DMB8MNU Patented CHIR-99021 increases the expression of Homeobox protein CDX-1 (CDX1). [30]
------------------------------------------------------------------------------------
⏷ Show the Full List of 8 Drug(s)

References

1 CDX1 expression is reduced in colorectal carcinoma and is associated with promoter hypermethylation.J Pathol. 2004 Nov;204(3):289-95. doi: 10.1002/path.1641.
2 LncRNA FOXD2-AS1 accelerates the progression of cervical cancer via downregulating CDX1.Eur Rev Med Pharmacol Sci. 2019 Dec;23(23):10234-10240. doi: 10.26355/eurrev_201912_19660.
3 Prognosis and modulation mechanisms of COMMD6 in human tumours based on expression profiling and comprehensive bioinformatics analysis.Br J Cancer. 2019 Oct;121(8):699-709. doi: 10.1038/s41416-019-0571-x. Epub 2019 Sep 16.
4 The homeobox gene Cdx1 belongs to the p53-p21(WAF)-Bcl-2 network in intestinal epithelial cells.Biochem Biophys Res Commun. 2002 Sep 27;297(3):607-15. doi: 10.1016/s0006-291x(02)02250-7.
5 Reducing DNA methylation suppresses colon carcinogenesis by inducing tumor cell differentiation.Carcinogenesis. 2015 Jul;36(7):719-29. doi: 10.1093/carcin/bgv060. Epub 2015 May 4.
6 A33 shows similar sensitivity to but is more specific than CDX2 as an immunomarker of colorectal carcinoma.Histopathology. 2017 Jul;71(1):34-41. doi: 10.1111/his.13194. Epub 2017 Apr 11.
7 Cdx1 homeobox gene during human colon cancer progression.Oncogene. 2003 Sep 11;22(39):7913-21. doi: 10.1038/sj.onc.1206756.
8 Hypoxia induces expression of COX-2 through the homeodomain transcription factor CDX1 and orphan nuclear receptor SHP in human endometrial cells. Mol Hum Reprod. 2011 Nov;17(11):710-9.
9 Methylation-dependent activation of CDX1 through NF-B: a link from inflammation to intestinal metaplasia in the human stomach.Am J Pathol. 2012 Aug;181(2):487-98. doi: 10.1016/j.ajpath.2012.04.028. Epub 2012 Jun 27.
10 Single nucleotide polymorphisms of caudal type homeobox 1 and 2 are associated with Barrett's esophagus.Dig Dis Sci. 2014 Jan;59(1):57-63. doi: 10.1007/s10620-013-2804-9. Epub 2013 Aug 6.
11 Low CDX1 expression predicts a poor prognosis for hepatocellular carcinoma patients after hepatectomy.Surg Oncol. 2016 Sep;25(3):171-7. doi: 10.1016/j.suronc.2016.05.026. Epub 2016 May 24.
12 Gene expression profiles in pancreatic intraepithelial neoplasia reflect the effects of Hedgehog signaling on pancreatic ductal epithelial cells.Cancer Res. 2005 Mar 1;65(5):1619-26. doi: 10.1158/0008-5472.CAN-04-1413.
13 CDX1 Expression Induced by CagA-Expressing Helicobacter pylori Promotes Gastric Tumorigenesis.Mol Cancer Res. 2019 Nov;17(11):2169-2183. doi: 10.1158/1541-7786.MCR-19-0181. Epub 2019 Aug 15.
14 Cdx1 inhibits the proliferation of human colon cancer cells by reducing cyclin D1 gene expression.Oncogene. 2003 Sep 25;22(41):6395-407. doi: 10.1038/sj.onc.1206770.
15 CDX-1 and CDX-2 are expressed in human colonic mucosa and are down-regulated in patients with Hirschsprung's disease associated enterocolitis.Biochim Biophys Acta. 2001 Sep 28;1537(2):89-100. doi: 10.1016/s0925-4439(01)00056-4.
16 Transduced caudal-type homeobox (CDX) 2/CDX1 can induce growth inhibition on CDX-deficient gastric cancer by rapid intestinal differentiation.Cancer Sci. 2018 Dec;109(12):3853-3864. doi: 10.1111/cas.13821. Epub 2018 Oct 26.
17 Sox2 expression in human stomach adenocarcinomas with gastric and gastric-and-intestinal-mixed phenotypes.Histopathology. 2005 Jun;46(6):649-58. doi: 10.1111/j.1365-2559.2005.02170.x.
18 CDX1/2 and KLF5 Expression and Epigenetic Modulation of Sonic Hedgehog Signaling in Gastric Adenocarcinoma.Pathol Oncol Res. 2019 Jul;25(3):1215-1222. doi: 10.1007/s12253-019-00594-4. Epub 2019 Jan 26.
19 Autophagy of cancer stem cells is involved with chemoresistance of colon cancer cells.Biochem Biophys Res Commun. 2013 May 17;434(4):898-903. doi: 10.1016/j.bbrc.2013.04.053. Epub 2013 Apr 23.
20 Methylation profile of the promoter CpG islands of 31 genes that may contribute to colorectal carcinogenesis.World J Gastroenterol. 2004 Dec 1;10(23):3441-54. doi: 10.3748/wjg.v10.i23.3441.
21 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.
22 Effect of chronic exposure to inorganic arsenic on intestinal cells. J Appl Toxicol. 2019 Jun;39(6):899-907. doi: 10.1002/jat.3778. Epub 2019 Feb 12.
23 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
24 Induction of intestinalization in human esophageal keratinocytes is a multistep process. Carcinogenesis. 2009 Jan;30(1):122-30. doi: 10.1093/carcin/bgn227. Epub 2008 Oct 8.
25 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.
26 Neuronal and cardiac toxicity of pharmacological compounds identified through transcriptomic analysis of human pluripotent stem cell-derived embryoid bodies. Toxicol Appl Pharmacol. 2021 Dec 15;433:115792. doi: 10.1016/j.taap.2021.115792. Epub 2021 Nov 3.
27 Differential regulation of proliferation, cell cycle control and gene expression in cultured human aortic and pulmonary artery endothelial cells by resveratrol. Int J Mol Med. 2010 Nov;26(5):743-9.
28 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.
29 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
30 Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells. Reprod Toxicol. 2020 Jan;91:74-91. doi: 10.1016/j.reprotox.2019.10.004. Epub 2019 Nov 8.
31 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.