Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR7AJHN)

• DOT Name: LIM domain only protein 3 (LMO3)
• Synonyms: LMO-3; Neuronal-specific transcription factor DAT1; Rhombotin-3
• Gene Name: LMO3
• Related Disease:
  Type-1 diabetes
  Advanced cancer
  B-cell lymphoma
  Ewing sarcoma
  Lung squamous cell carcinoma
  Mood disorder
  Obesity
  Lung adenocarcinoma
  Tourette syndrome
  Gastric cancer
  Hepatocellular carcinoma
  Neuroblastoma
  Stomach cancer
• UniProt ID: LMO3_HUMAN
• Pfam ID: PF00412
• Sequence:
  MLSVQPDTKPKGCAGCNRKIKDRYLLKALDKYWHEDCLKCACCDCRLGEVGSTLYTKANL
  ILCRRDYLRLFGVTGNCAACSKLIPAFEMVMRAKDNVYHLDCFACQLCNQRFCVGDKFFL
  KNNMILCQTDYEEGLMKEGYAPQVR

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Type-1 diabetes	DIS7HLUB	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[3]
Ewing sarcoma	DISQYLV3	Strong	Biomarker	[4]
Lung squamous cell carcinoma	DISXPIBD	Strong	Biomarker	[5]
Mood disorder	DISLVMWO	Strong	Biomarker	[6]
Obesity	DIS47Y1K	Strong	Biomarker	[7]
Lung adenocarcinoma	DISD51WR	moderate	Biomarker	[8]
Tourette syndrome	DISX9D54	moderate	Genetic Variation	[9]
Gastric cancer	DISXGOUK	Limited	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[11]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[12]
Stomach cancer	DISKIJSX	Limited	Biomarker	[10]

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 LIM domain only protein 3 (LMO3).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of LIM domain only protein 3 (LMO3).	[24]

15 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 LIM domain only protein 3 (LMO3).	[14]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of LIM domain only protein 3 (LMO3).	[15]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of LIM domain only protein 3 (LMO3).	[16]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of LIM domain only protein 3 (LMO3).	[17]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of LIM domain only protein 3 (LMO3).	[18]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of LIM domain only protein 3 (LMO3).	[19]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of LIM domain only protein 3 (LMO3).	[20]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of LIM domain only protein 3 (LMO3).	[21]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of LIM domain only protein 3 (LMO3).	[19]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of LIM domain only protein 3 (LMO3).	[22]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of LIM domain only protein 3 (LMO3).	[23]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of LIM domain only protein 3 (LMO3).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of LIM domain only protein 3 (LMO3).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of LIM domain only protein 3 (LMO3).	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of LIM domain only protein 3 (LMO3).	[27]

References

• [1] BTNL2-Ig Protein Attenuates Type 1 Diabetes in Non-Obese Diabetic (NOD) Mice.Adv Healthc Mater. 2019 May;8(9):e1800987. doi: 10.1002/adhm.201800987. Epub 2019 Mar 18.
• [2] Integrative genomics identifies LMO1 as a neuroblastoma oncogene.Nature. 2011 Jan 13;469(7329):216-20. doi: 10.1038/nature09609. Epub 2010 Dec 1.
• [3] Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B-cell lymphoma cells and their association with clinical features.Cancer Med. 2016 Aug;5(8):1802-9. doi: 10.1002/cam4.753. Epub 2016 May 17.
• [4] Newly identified LMO3-BORCS5 fusion oncogene in Ewing sarcoma at relapse is a driver of tumor progression.Oncogene. 2019 Nov;38(47):7200-7215. doi: 10.1038/s41388-019-0914-3. Epub 2019 Sep 5.
• [5] Genome-wide analysis of DNA methylation and the gene expression change in lung cancer.J Thorac Oncol. 2012 Jan;7(1):20-33. doi: 10.1097/JTO.0b013e3182307f62.
• [6] Lmo3 deficiency in the mouse is associated with alterations in mood-related behaviors and a depression-biased amygdala transcriptome.Psychoneuroendocrinology. 2020 Jan;111:104480. doi: 10.1016/j.psyneuen.2019.104480. Epub 2019 Oct 19.
• [7] Human but not mouse adipogenesis is critically dependent on LMO3.Cell Metab. 2013 Jul 2;18(1):62-74. doi: 10.1016/j.cmet.2013.05.020.
• [8] MicroRNA-381 inhibits lung adenocarcinoma cell biological progression by directly targeting LMO3 through regulation of the PI3K/Akt signaling pathway and epithelial-to-mesenchymal transition.Eur Rev Med Pharmacol Sci. 2019 Oct;23(19):8411-8421. doi: 10.26355/eurrev_201910_19152.
• [9] Interrogating the Genetic Determinants of Tourette's Syndrome and Other Tic Disorders Through Genome-Wide Association Studies.Am J Psychiatry. 2019 Mar 1;176(3):217-227. doi: 10.1176/appi.ajp.2018.18070857.
• [10] LMO3 promotes gastric cancer cell invasion and proliferation through Akt-mTOR and Akt-GSK3 signaling.Int J Mol Med. 2018 May;41(5):2755-2763. doi: 10.3892/ijmm.2018.3476. Epub 2018 Feb 8.
• [11] LMO3 promotes hepatocellular carcinoma invasion, metastasis and anoikis inhibition by directly interacting with LATS1 and suppressing Hippo signaling.J Exp Clin Cancer Res. 2018 Sep 15;37(1):228. doi: 10.1186/s13046-018-0903-3.
• [12] Oncogenic LMO3 collaborates with HEN2 to enhance neuroblastoma cell growth through transactivation of Mash1.PLoS One. 2011 May 5;6(5):e19297. doi: 10.1371/journal.pone.0019297.
• [13] 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.
• [14] Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound. Toxicol In Vitro. 2021 Jun;73:105112. doi: 10.1016/j.tiv.2021.105112. Epub 2021 Feb 22.
• [15] 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.
• [16] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [17] 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.
• [18] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [19] 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.
• [20] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [21] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [22] Genistein disrupts glucocorticoid receptor signaling in human uterine endometrial Ishikawa cells. Environ Health Perspect. 2015 Jan;123(1):80-7. doi: 10.1289/ehp.1408437. Epub 2014 Aug 19.
• [23] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [24] 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.
• [25] 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.
• [26] The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.
• [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.