Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMG7RWW)

• DOT Name: Armadillo repeat-containing X-linked protein 3 (ARMCX3)
• Synonyms: ARM protein lost in epithelial cancers on chromosome X 3; Protein ALEX3
• Gene Name: ARMCX3
• Related Disease:
  Lung cancer
  Lung carcinoma
  Non-small-cell lung cancer
• UniProt ID: ARMX3_HUMAN
• Pfam ID: PF04826
• Sequence:
  MGYARKVGWVTAGLVIGAGACYCIYRLTRGRKQNKEKMAEGGSGDVDDAGDCSGARYNDW
  SDDDDDSNESKSIVWYPPWARIGTEAGTRARARARARATRARRAVQKRASPNSDDTVLSP
  QELQKVLCLVEMSEKPYILEAALIALGNNAAYAFNRDIIRDLGGLPIVAKILNTRDPIVK
  EKALIVLNNLSVNAENQRRLKVYMNQVCDDTITSRLNSSVQLAGLRLLTNMTVTNEYQHM
  LANSISDFFRLFSAGNEETKLQVLKLLLNLAENPAMTRELLRAQVPSSLGSLFNKKENKE
  VILKLLVIFENINDNFKWEENEPTQNQFGEGSLFFFLKEFQVCADKVLGIESHHDFLVKV
  KVGKFMAKLAEHMFPKSQE
• Function: Regulates mitochondrial aggregation and transport in axons in living neurons. May link mitochondria to the TRAK2-kinesin motor complex via its interaction with Miro and TRAK2. Mitochondrial distribution and dynamics is regulated through ARMCX3 protein degradation, which is promoted by PCK and negatively regulated by WNT1. Enhances the SOX10-mediated transactivation of the neuronal acetylcholine receptor subunit alpha-3 and beta-4 subunit gene promoters.
• Reactome Pathway: RAC2 GTPase cycle (R-HSA-9013404)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Strong	Altered Expression	[1]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Armadillo repeat-containing X-linked protein 3 (ARMCX3).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Armadillo repeat-containing X-linked protein 3 (ARMCX3).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Armadillo repeat-containing X-linked protein 3 (ARMCX3).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Armadillo repeat-containing X-linked protein 3 (ARMCX3).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Armadillo repeat-containing X-linked protein 3 (ARMCX3).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Armadillo repeat-containing X-linked protein 3 (ARMCX3).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Armadillo repeat-containing X-linked protein 3 (ARMCX3).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Armadillo repeat-containing X-linked protein 3 (ARMCX3).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Armadillo repeat-containing X-linked protein 3 (ARMCX3).	[10]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Armadillo repeat-containing X-linked protein 3 (ARMCX3).	[11]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Armadillo repeat-containing X-linked protein 3 (ARMCX3).	[12]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Armadillo repeat-containing X-linked protein 3 (ARMCX3).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Armadillo repeat-containing X-linked protein 3 (ARMCX3).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Armadillo repeat-containing X-linked protein 3 (ARMCX3).	[16]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Armadillo repeat-containing X-linked protein 3 (ARMCX3).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Armadillo repeat-containing X-linked protein 3 (ARMCX3).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Armadillo repeat-containing X-linked protein 3 (ARMCX3).	[14]

References

• [1] Alex3 suppresses non-small cell lung cancer invasion via AKT/Slug/E-cadherin pathway.Tumour Biol. 2017 Jul;39(7):1010428317701441. doi: 10.1177/1010428317701441.
• [2] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [3] 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.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] 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.
• [8] Arsenic targets Pin1 and cooperates with retinoic acid to inhibit cancer-driving pathways and tumor-initiating cells. Nat Commun. 2018 Aug 9;9(1):3069. doi: 10.1038/s41467-018-05402-2.
• [9] 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.
• [10] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [11] 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.
• [12] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [13] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [14] 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.
• [15] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [16] 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.
• [17] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [18] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.