Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6Y8IEK)

• DOT Name: LIM domain-binding protein 2 (LDB2)
• Synonyms: LDB-2; Carboxyl-terminal LIM domain-binding protein 1; CLIM-1; LIM domain-binding factor CLIM1
• Gene Name: LDB2
• Related Disease:
  Coronary atherosclerosis
  Lung adenocarcinoma
  Carcinoma of liver and intrahepatic biliary tract
  Hepatocellular carcinoma
  Liver cancer
  Arteriosclerosis
  Atherosclerosis
  Coronary heart disease
• UniProt ID: LDB2_HUMAN
• Pfam ID: PF17916 ; PF01803
• Sequence:
  MSSTPHDPFYSSPFGPFYRRHTPYMVQPEYRIYEMNKRLQSRTEDSDNLWWDAFATEFFE
  DDATLTLSFCLEDGPKRYTIGRTLIPRYFSTVFEGGVTDLYYILKHSKESYHNSSITVDC
  DQCTMVTQHGKPMFTKVCTEGRLILEFTFDDLMRIKTWHFTIRQYRELVPRSILAMHAQD
  PQVLDQLSKNITRMGLTNFTLNYLRLCVILEPMQELMSRHKTYNLSPRDCLKTCLFQKWQ
  RMVAPPAEPTRQPTTKRRKRKNSTSSTSNSSAGNNANSTGSKKKTTAANLSLSSQVPDVM
  VVGEPTLMGGEFGDEDERLITRLENTQYDAANGMDDEEDFNNSPALGNNSPWNSKPPATQ
  ETKSENPPPQASQ
• Function: Transcription cofactor. Binds to the LIM domain of a wide variety of LIM domain-containing transcription factors.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[1]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[2]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	moderate	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[3]
Liver cancer	DISDE4BI	moderate	Biomarker	[3]
Arteriosclerosis	DISK5QGC	Limited	Altered Expression	[4]
Atherosclerosis	DISMN9J3	Limited	Altered Expression	[4]
Coronary heart disease	DIS5OIP1	Limited	Altered Expression	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of LIM domain-binding protein 2 (LDB2).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of LIM domain-binding protein 2 (LDB2).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of LIM domain-binding protein 2 (LDB2).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of LIM domain-binding protein 2 (LDB2).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of LIM domain-binding protein 2 (LDB2).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of LIM domain-binding protein 2 (LDB2).	[10]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of LIM domain-binding protein 2 (LDB2).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of LIM domain-binding protein 2 (LDB2).	[12]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of LIM domain-binding protein 2 (LDB2).	[13]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of LIM domain-binding protein 2 (LDB2).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of LIM domain-binding protein 2 (LDB2).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of LIM domain-binding protein 2 (LDB2).	[17]

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 decreases the methylation of LIM domain-binding protein 2 (LDB2).	[15]

References

• [1] Multi-organ expression profiling uncovers a gene module in coronary artery disease involving transendothelial migration of leukocytes and LIM domain binding 2: the Stockholm Atherosclerosis Gene Expression (STAGE) study.PLoS Genet. 2009 Dec;5(12):e1000754. doi: 10.1371/journal.pgen.1000754. Epub 2009 Dec 4.
• [2] A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma.Am J Hum Genet. 2009 Nov;85(5):679-91. doi: 10.1016/j.ajhg.2009.09.012. Epub 2009 Oct 15.
• [3] LDB2 inhibits proliferation and migration in liver cancer cells by abrogating HEY1 expression.Oncotarget. 2017 Oct 10;8(55):94440-94449. doi: 10.18632/oncotarget.21772. eCollection 2017 Nov 7.
• [4] Lim domain binding 2: a key driver of transendothelial migration of leukocytes and atherosclerosis.Arterioscler Thromb Vasc Biol. 2014 Sep;34(9):2068-77. doi: 10.1161/ATVBAHA.113.302709. Epub 2014 Jun 12.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] 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.
• [7] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [13] Transcriptional profiling in the human prefrontal cortex: evidence for two activational states associated with cocaine abuse. Pharmacogenomics J. 2003;3(1):27-40.
• [14] 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.
• [15] 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.
• [16] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [17] 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.