Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1CPNCC)

• DOT Name: Protein limb expression 1 homolog (LIX1)
• Gene Name: LIX1
• Related Disease:
  Neoplasm
  Cholelithiasis
  Hepatitis C virus infection
  Spinal muscular atrophy
• UniProt ID: LIX1_HUMAN
• Pfam ID: PF14954
• Sequence:
  MDRTLESLRHIIAQVLPHRDPALVFKDLNVVSMLQEFWESKQQQKAAFPSEGVVVYESLP
  APGPPFVSYVTLPGGSCFGNFQCCLSRAEARRDAAKVALINSLFNELPSRRITKEFIMES
  VQEAVASTSGTLDDADDPSTSVGAYHYMLESNMGKTMLEFQELMTIFQLLHWNGSLKALR
  ETKCSRQEVISYYSQYSLDEKMRSHMALDWIMKERDSPGIVSQELRMALRQLEEARKAGQ
  ELRFYKEKKEILSLALTQICSDPDTSSPSDDQLSLTALCGYH

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Cholelithiasis	DISERLZB	Strong	Biomarker	[2]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[3]
Spinal muscular atrophy	DISTLKOB	moderate	Genetic Variation	[4]

14 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 Protein limb expression 1 homolog (LIX1).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein limb expression 1 homolog (LIX1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein limb expression 1 homolog (LIX1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein limb expression 1 homolog (LIX1).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Protein limb expression 1 homolog (LIX1).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Protein limb expression 1 homolog (LIX1).	[10]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Protein limb expression 1 homolog (LIX1).	[11]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Protein limb expression 1 homolog (LIX1).	[12]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of Protein limb expression 1 homolog (LIX1).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Protein limb expression 1 homolog (LIX1).	[11]
Genistein	DM0JETC	Phase 2/3	Genistein affects the expression of Protein limb expression 1 homolog (LIX1).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein limb expression 1 homolog (LIX1).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Protein limb expression 1 homolog (LIX1).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein limb expression 1 homolog (LIX1).	[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 increases the methylation of Protein limb expression 1 homolog (LIX1).	[14]

References

• [1] A study on the role of (+)-catechin in suppression of HepG2 proliferation via caspase dependent pathway and enhancement of its in vitro and in vivo cytotoxic potential through liposomal formulation.Eur J Pharm Sci. 2013 Nov 20;50(3-4):353-65. doi: 10.1016/j.ejps.2013.08.005. Epub 2013 Aug 15.
• [2] Single hospital visit elective day-case laparoscopic cholecystectomy without prior outpatient attendance.Surg Endosc. 2017 Sep;31(9):3574-3580. doi: 10.1007/s00464-016-5387-7. Epub 2017 Jan 26.
• [3] Screening of hepatitis C virus genotypes in urticaria patients in Saudi Arabia.Genet Test Mol Biomarkers. 2012 Aug;16(8):964-7. doi: 10.1089/gtmb.2012.0014. Epub 2012 Jul 12.
• [4] Screening of the LIX1 gene in Japanese and Malaysian patients with SMA and/or SMA-like disorder.Brain Dev. 2010 May;32(5):385-9. doi: 10.1016/j.braindev.2009.06.008. Epub 2009 Aug 6.
• [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] 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.
• [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] 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] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [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] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [13] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [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] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [16] 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.
• [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.