Details of Drug Off-Target (DOT)

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

• DOT Name: Chloride channel CLIC-like protein 1 (CLCC1)
• Synonyms: Mid-1-related chloride channel protein 1
• Gene Name: CLCC1
• UniProt ID: CLCC1_HUMAN
• Pfam ID: PF05934
• Sequence:
  MLCSLLLCECLLLVAGYAHDDDWIDPTDMLNYDAASGTMRKSQAKYGISGEKDVSPDLSC
  ADEISECYHKLDSLTYKIDECEKKKREDYESQSNPVFRRYLNKILIEAGKLGLPDENKGD
  MHYDAEIILKRETLLEIQKFLNGEDWKPGALDDALSDILINFKFHDFETWKWRFEDSFGV
  DPYNVLMVLLCLLCIVVLVATELWTYVRWYTQLRRVLIISFLFSLGWNWMYLYKLAFAQH
  QAEVAKMEPLNNVCAKKMDWTGSIWEWFRSSWTYKDDPCQKYYELLLVNPIWLVPPTKAL
  AVTFTTFVTEPLKHIGKGTGEFIKALMKEIPALLHLPVLIIMALAILSFCYGAGKSVHVL
  RHIGGPESEPPQALRPRDRRRQEEIDYRPDGGAGDADFHYRGQMGPTEQGPYAKTYEGRR
  EILRERDVDLRFQTGNKSPEVLRAFDVPDAEAREHPTVVPSHKSPVLDTKPKETGGILGE
  GTPKESSTESSQSAKPVSGQDTSGNTEGSPAAEKAQLKSEAAGSPDQGSTYSPARGVAGP
  RGQDPVSSPCG
• Function: Seems to act as a chloride ion channel. Plays a role in retina development.
• Tissue Specificity: Expressed in the retina of the eye, with extensive expression in the lamina cribrosa, optic nerve, ganglion cell layer, inner nuclear layer, outer nuclear layer and retinal pigment epithelium.

Molecular Interaction Atlas (MIA) of This DOT

11 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 Chloride channel CLIC-like protein 1 (CLCC1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Chloride channel CLIC-like protein 1 (CLCC1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Chloride channel CLIC-like protein 1 (CLCC1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Chloride channel CLIC-like protein 1 (CLCC1).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Chloride channel CLIC-like protein 1 (CLCC1).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Chloride channel CLIC-like protein 1 (CLCC1).	[6]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Chloride channel CLIC-like protein 1 (CLCC1).	[7]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Chloride channel CLIC-like protein 1 (CLCC1).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Chloride channel CLIC-like protein 1 (CLCC1).	[7]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Chloride channel CLIC-like protein 1 (CLCC1).	[11]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Chloride channel CLIC-like protein 1 (CLCC1).	[12]

3 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 Chloride channel CLIC-like protein 1 (CLCC1).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Chloride channel CLIC-like protein 1 (CLCC1).	[10]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Chloride channel CLIC-like protein 1 (CLCC1).	[10]

References

• [1] 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.
• [2] 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.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] 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.
• [5] 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.
• [6] Aberrantly expressed genes in HaCaT keratinocytes chronically exposed to arsenic trioxide. Biomark Insights. 2011 Feb 8;6:7-16.
• [7] 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.
• [8] Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
• [9] 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.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [11] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [12] Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):73-88.