Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJEMT2D)

• DOT Name: Homeobox protein MOX-1 (MEOX1)
• Synonyms: Mesenchyme homeobox 1
• Gene Name: MEOX1
• Related Disease:
  Allergic contact dermatitis
  Breast cancer
  Breast carcinoma
  Cardiac failure
  Congestive heart failure
  Disorder of sexual differentiation
  Familial dilated cardiomyopathy
  Familial hypertrophic cardiomyopathy
  Hyperostosis corticalis generalisata
  Hypertrophic cardiomyopathy
  Klippel-Feil syndrome
  Klippel-Feil syndrome 1, autosomal dominant
  Klippel-Feil syndrome 2, autosomal recessive
  Ovarian cancer
  Prostate cancer
  Prostate carcinoma
  Sclerosteosis
  Smith-McCort dysplasia 1
  Lung cancer
  Lung carcinoma
  Lung squamous cell carcinoma
  Non-small-cell lung cancer
  Obsolete isolated Klippel-Feil syndrome
• UniProt ID: MEOX1_HUMAN
• Pfam ID: PF00046
• Sequence:
  MDPAASSCMRSLQPPAPVWGCLRNPHSEGNGASGLPHYPPTPFSFHQKPDFLATATAAYP
  DFSASCLAATPHSLPQEEHIFTEQHPAFPQSPNWHFPVSDARRRPNSGPAGGSKEMGTSS
  LGLVDTTGGPGDDYGVLGSTANETEKKSSRRRKESSDNQENRGKPEGSSKARKERTAFTK
  EQLRELEAEFAHHNYLTRLRRYEIAVNLDLSERQVKVWFQNRRMKWKRVKGGQPISPNGQ
  DPEDGDSTASPSSE
• Function: Mesodermal transcription factor that plays a key role in somitogenesis and is specifically required for sclerotome development. Required for maintenance of the sclerotome polarity and formation of the cranio-cervical joints. Binds specifically to the promoter of target genes and regulates their expression. Activates expression of NKX3-2 in the sclerotome. Activates expression of CDKN1A and CDKN2A in endothelial cells, acting as a regulator of vascular cell proliferation. While it activates CDKN1A in a DNA-dependent manner, it activates CDKN2A in a DNA-independent manner. Required for hematopoietic stem cell (HSCs) induction via its role in somitogenesis: specification of HSCs occurs via the deployment of a specific endothelial precursor population, which arises within a sub-compartment of the somite named endotome.

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Allergic contact dermatitis	DISFFVF9	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Cardiac failure	DISDC067	Strong	Altered Expression	[3]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[3]
Disorder of sexual differentiation	DISRMAEZ	Strong	Biomarker	[4]
Familial dilated cardiomyopathy	DISBHDU9	Strong	Altered Expression	[3]
Familial hypertrophic cardiomyopathy	DISQ89HN	Strong	Biomarker	[3]
Hyperostosis corticalis generalisata	DISR4BHB	Strong	Biomarker	[5]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Altered Expression	[3]
Klippel-Feil syndrome	DISRVCYV	Strong	Genetic Variation	[6]
Klippel-Feil syndrome 1, autosomal dominant	DISKGBD8	Strong	Autosomal recessive	[7]
Klippel-Feil syndrome 2, autosomal recessive	DISZ0FWV	Strong	Autosomal recessive	[8]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[9]
Prostate cancer	DISF190Y	Strong	Altered Expression	[10]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[10]
Sclerosteosis	DISB8RTM	Strong	Biomarker	[5]
Smith-McCort dysplasia 1	DIS8072R	Strong	Altered Expression	[11]
Lung cancer	DISCM4YA	moderate	Biomarker	[2]
Lung carcinoma	DISTR26C	moderate	Biomarker	[2]
Lung squamous cell carcinoma	DISXPIBD	moderate	Altered Expression	[2]
Non-small-cell lung cancer	DIS5Y6R9	moderate	Altered Expression	[2]
Obsolete isolated Klippel-Feil syndrome	DISI44BI	Supportive	Autosomal dominant	[8]

2 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 MOX-1 (MEOX1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Homeobox protein MOX-1 (MEOX1).	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Homeobox protein MOX-1 (MEOX1).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Homeobox protein MOX-1 (MEOX1).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Homeobox protein MOX-1 (MEOX1).	[15]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Homeobox protein MOX-1 (MEOX1).	[16]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Homeobox protein MOX-1 (MEOX1).	[17]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Homeobox protein MOX-1 (MEOX1).	[18]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Homeobox protein MOX-1 (MEOX1).	[19]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Homeobox protein MOX-1 (MEOX1).	[20]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Homeobox protein MOX-1 (MEOX1).	[21]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Homeobox protein MOX-1 (MEOX1).	[13]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Homeobox protein MOX-1 (MEOX1).	[18]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Homeobox protein MOX-1 (MEOX1).	[13]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Homeobox protein MOX-1 (MEOX1).	[22]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Homeobox protein MOX-1 (MEOX1).	[23]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of Homeobox protein MOX-1 (MEOX1).	[24]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Homeobox protein MOX-1 (MEOX1).	[25]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the expression of Homeobox protein MOX-1 (MEOX1).	[13]
Phenytoin	DMNOKBV	Approved	Phenytoin decreases the expression of Homeobox protein MOX-1 (MEOX1).	[13]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Homeobox protein MOX-1 (MEOX1).	[25]
Vitamin A	DMJ2AH4	Approved	Vitamin A increases the expression of Homeobox protein MOX-1 (MEOX1).	[25]
Nilotinib	DM7HXWT	Approved	Nilotinib decreases the expression of Homeobox protein MOX-1 (MEOX1).	[13]
Abacavir	DMMN36E	Approved	Abacavir decreases the expression of Homeobox protein MOX-1 (MEOX1).	[13]
Polyethylene glycol	DM4I1JP	Approved	Polyethylene glycol decreases the expression of Homeobox protein MOX-1 (MEOX1).	[13]
Dabigatran	DMDI6R4	Approved	Dabigatran decreases the expression of Homeobox protein MOX-1 (MEOX1).	[13]
Ramelteon	DM7IW9J	Approved	Ramelteon decreases the expression of Homeobox protein MOX-1 (MEOX1).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Homeobox protein MOX-1 (MEOX1).	[18]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Homeobox protein MOX-1 (MEOX1).	[22]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Homeobox protein MOX-1 (MEOX1).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Homeobox protein MOX-1 (MEOX1).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Homeobox protein MOX-1 (MEOX1).	[27]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Homeobox protein MOX-1 (MEOX1).	[28]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid increases the expression of Homeobox protein MOX-1 (MEOX1).	[25]

References

• [1] Gene transcripts as potential diagnostic markers for allergic contact dermatitis.Contact Dermatitis. 2005 Aug;53(2):100-6. doi: 10.1111/j.0105-1873.2005.00658.x.
• [2] MEOX1 Promotes Tumor Progression and Predicts Poor Prognosis in Human Non-Small-Cell Lung Cancer.Int J Med Sci. 2019 Jan 1;16(1):68-74. doi: 10.7150/ijms.27595. eCollection 2019.
• [3] Meox1 accelerates myocardial hypertrophic decompensation through Gata4.Cardiovasc Res. 2018 Feb 1;114(2):300-311. doi: 10.1093/cvr/cvx222.
• [4] Diaphanospondylodysostosis: six new cases and exclusion of the candidate genes, PAX1 and MEOX1.Am J Med Genet A. 2007 Oct 1;143A(19):2292-302. doi: 10.1002/ajmg.a.31934.
• [5] A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12-q21 is associated with van Buchem disease in the Dutch population.Am J Med Genet. 2002 Jun 15;110(2):144-52. doi: 10.1002/ajmg.10401.
• [6] Skeletal malformations of Meox1-deficient zebrafish resemble human Klippel-Feil syndrome.J Anat. 2018 Dec;233(6):687-695. doi: 10.1111/joa.12890. Epub 2018 Oct 2.
• [7] Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
• [8] Mutations in MEOX1, encoding mesenchyme homeobox 1, cause Klippel-Feil anomaly. Am J Hum Genet. 2013 Jan 10;92(1):157-61. doi: 10.1016/j.ajhg.2012.11.016. Epub 2013 Jan 3.
• [9] Identification of PBX1 target genes in cancer cells by global mapping of PBX1 binding sites.PLoS One. 2012;7(5):e36054. doi: 10.1371/journal.pone.0036054. Epub 2012 May 2.
• [10] Silencing of MEOX1 Gene Inhibits Proliferation and Promotes Apoptosis of LNCaP Cells in Prostate Cancer.Cancer Biother Radiopharm. 2019 Mar;34(2):91-102. doi: 10.1089/cbr.2018.2545. Epub 2018 Dec 12.
• [11] Mesoderm/mesenchyme homeobox gene l promotes vascular smooth muscle cell phenotypic modulation and vascular remodeling.Int J Cardiol. 2018 Jan 15;251:82-89. doi: 10.1016/j.ijcard.2017.10.098. Epub 2017 Oct 31.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [16] 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.
• [17] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [18] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [19] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [20] 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.
• [21] 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.
• [22] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [23] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [24] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [25] Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
• [26] 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.
• [27] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [28] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.