Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0DFL7C)

• DOT Name: LIM/homeobox protein Lhx8 (LHX8)
• Synonyms: LIM homeobox protein 8
• Gene Name: LHX8
• Related Disease:
  Carcinoma
  Cervical cancer
  Cervical carcinoma
  Cervical Intraepithelial neoplasia
  Cervix disorder
  Immunodeficiency
  Tourette syndrome
  Female hypogonadism
• UniProt ID: LHX8_HUMAN
• Pfam ID: PF00046 ; PF00412
• Sequence:
  MQILSRCQGLMSEECGRTTALAAGRTRKGAGEEGLVSPEGAGDEDSCSSSAPLSPSSSPR
  SMASGSGCPPGKCVCNSCGLEIVDKYLLKVNDLCWHVRCLSCSVCRTSLGRHTSCYIKDK
  DIFCKLDYFRRYGTRCSRCGRHIHSTDWVRRAKGNVYHLACFACFSCKRQLSTGEEFALV
  EEKVLCRVHYDCMLDNLKREVENGNGISVEGALLTEQDVNHPKPAKRARTSFTADQLQVM
  QAQFAQDNNPDAQTLQKLAERTGLSRRVIQVWFQNCRARHKKHVSPNHSSSTPVTAVPPS
  RLSPPMLEEMAYSAYVPQDGTMLTALHSYMDAHSPTTLGLQPLLPHSMTQLPISHT
• Function: Transcription factor involved in differentiation of certain neurons and mesenchymal cells.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Strong	Posttranslational Modification	[1]
Cervical cancer	DISFSHPF	Strong	Biomarker	[1]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[1]
Cervical Intraepithelial neoplasia	DISXP757	Strong	Biomarker	[1]
Cervix disorder	DIS1HG31	Strong	Altered Expression	[1]
Immunodeficiency	DIS093I0	Strong	Genetic Variation	[2]
Tourette syndrome	DISX9D54	Strong	Altered Expression	[3]
Female hypogonadism	DISWASB4	moderate	Genetic Variation	[4]

11 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 LIM/homeobox protein Lhx8 (LHX8).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of LIM/homeobox protein Lhx8 (LHX8).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of LIM/homeobox protein Lhx8 (LHX8).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of LIM/homeobox protein Lhx8 (LHX8).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of LIM/homeobox protein Lhx8 (LHX8).	[10]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of LIM/homeobox protein Lhx8 (LHX8).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of LIM/homeobox protein Lhx8 (LHX8).	[11]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of LIM/homeobox protein Lhx8 (LHX8).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of LIM/homeobox protein Lhx8 (LHX8).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of LIM/homeobox protein Lhx8 (LHX8).	[14]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of LIM/homeobox protein Lhx8 (LHX8).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of LIM/homeobox protein Lhx8 (LHX8).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of LIM/homeobox protein Lhx8 (LHX8).	[12]

References

• [1] Detection of hypermethylated genes as markers for cervical screening in women living with HIV.J Int AIDS Soc. 2018 Aug;21(8):e25165. doi: 10.1002/jia2.25165.
• [2] Zearalenone exposure impairs ovarian primordial follicle formation via down-regulation of Lhx8 expression in vitro.Toxicol Appl Pharmacol. 2017 Feb 15;317:33-40. doi: 10.1016/j.taap.2017.01.004. Epub 2017 Jan 12.
• [3] Evaluation of the LIM homeobox genes LHX6 and LHX8 as candidates for Tourette syndrome.Genes Brain Behav. 2012 Jun;11(4):444-51. doi: 10.1111/j.1601-183X.2012.00778.x. Epub 2012 Apr 11.
• [4] Analysis of LHX8 mutation in premature ovarian failure.Fertil Steril. 2008 Apr;89(4):1012-4. doi: 10.1016/j.fertnstert.2007.04.017. Epub 2007 Jul 10.
• [5] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [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] 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.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics. 2014 May;9(5):774-82. doi: 10.4161/epi.28153. Epub 2014 Feb 13.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.