Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFMSU5U)

• DOT Name: Chloride intracellular channel protein 6 (CLIC6)
• Synonyms: Parchorin
• Gene Name: CLIC6
• UniProt ID: CLIC6_HUMAN
• Pfam ID: PF13409
• Sequence:
  MAEAAEPEGVAPGPQGPPEVPAPLAERPGEPGAAGGEAEGPEGSEGAEEAPRGAAAVKEA
  GGGGPDRGPEAEARGTRGAHGETEAEEGAPEGAEVPQGGEETSGAQQVEGASPGRGAQGE
  PRGEAQREPEDSAAPERQEEAEQRPEVPEGSASGEAGDSVDAEGPLGDNIEAEGPAGDSV
  EAEGRVGDSVDAEGPAGDSVDAEGPLGDNIQAEGPAGDSVDAEGRVGDSVDAEGPAGDSV
  DAEGRVGDSVEAGDPAGDGVEAGVPAGDSVEAEGPAGDSMDAEGPAGRARRVSGEPQQSG
  DGSLSPQAEAIEVAAGESAGRSPGELAWDAAEEAEVPGVKGSEEAAPGDARADAGEDRVG
  DGPQQEPGEDEERRERSPEGPREEEAAGGEEESPDSSPHGEASRGAAEPEAQLSNHLAEE
  GPAEGSGEAARVNGRREDGEASEPRALGQEHDITLFVKVKLTALGCSRIAIKKYLRAGYD
  GESIGNCPFSQRLFMILWLKGVIFNVTTVDLKRKPADLQNLAPGTNPPFMTFDGEVKTDV
  NKIEEFLEEKLAPPRYPKLGTQHPESNSAGNDVFAKFSAFIKNTKKDANEIHEKNLLKAL
  RKLDNYLNSPLPDEIDAYSTEDVTVSGRKFLDGDELTLADCNLLPKLHIIKIVAKKYRDF
  EFPSEMTGIWRYLNNAYARDEFTNTCPADQEIEHAYSDVAKRMK
• Function: May insert into membranes and form chloride ion channels. May play a critical role in water-secreting cells, possibly through the regulation of chloride ion transport.
• Tissue Specificity: Expressed in brain, placenta, pancreas and liver.

Molecular Interaction Atlas (MIA) of This DOT

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 Chloride intracellular channel protein 6 (CLIC6).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Chloride intracellular channel protein 6 (CLIC6).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Chloride intracellular channel protein 6 (CLIC6).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Chloride intracellular channel protein 6 (CLIC6).	[3]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Chloride intracellular channel protein 6 (CLIC6).	[2]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Chloride intracellular channel protein 6 (CLIC6).	[4]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Chloride intracellular channel protein 6 (CLIC6).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Chloride intracellular channel protein 6 (CLIC6).	[4]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Chloride intracellular channel protein 6 (CLIC6).	[3]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Chloride intracellular channel protein 6 (CLIC6).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Chloride intracellular channel protein 6 (CLIC6).	[3]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Chloride intracellular channel protein 6 (CLIC6).	[8]

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] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [3] Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
• [4] 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.
• [5] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [6] 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.
• [7] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [8] 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.