Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL0FT8L)

• DOT Name: Choline transporter-like protein 3 (SLC44A3)
• Synonyms: Solute carrier family 44 member 3
• Gene Name: SLC44A3
• Related Disease: Epilepsy
• UniProt ID: CTL3_HUMAN
• Pfam ID: PF04515
• Sequence:
  MHCLGAEYLVSAEGAPRQREWRPQIYRKCTDTAWLFLFFLFWTGLVFIMGYSVVAGAAGR
  LLFGYDSFGNMCGKKNSPVEGAPLSGQDMTLKKHVFFMNSCNLEVKGTQLNRMALCVSNC
  PEEQLDSLEEVQFFANTSGSFLCVYSLNSFNYTHSPKADSLCPRLPVPPSKSFPLFNRCV
  PQTPECYSLFASVLINDVDTLHRILSGIMSGRDTILGLCILALALSLAMMFTFRFITTLL
  VHIFISLVILGLLFVCGVLWWLYYDYTNDLSIELDTERENMKCVLGFAIVSTGITAVLLV
  LIFVLRKRIKLTVELFQITNKAISSAPFLLFQPLWTFAILIFFWVLWVAVLLSLGTAGAA
  QVMEGGQVEYKPLSGIRYMWSYHLIGLIWTSEFILACQQMTIAGAVVTCYFNRSKNDPPD
  HPILSSLSILFFYHQGTVVKGSFLISVVRIPRIIVMYMQNALKEQQHGALSRYLFRCCYC
  CFWCLDKYLLHLNQNAYTTTAINGTDFCTSAKDAFKILSKNSSHFTSINCFGDFIIFLGK
  VLVVCFTVFGGLMAFNYNRAFQVWAVPLLLVAFFAYLVAHSFLSVFETVLDALFLCFAVD
  LETNDGSSEKPYFMDQEFLSFVKRSNKLNNARAQQDKHSLRNEEGTELQAIVR
• KEGG Pathway: Choline metabolism in cancer (hsa05231)
• Reactome Pathway:
  Transport of bile salts and organic acids, metal ions and amine compounds (R-HSA-425366)
  Synthesis of PC (R-HSA-1483191)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epilepsy	DISBB28L	Strong	Biomarker	[1]

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 Choline transporter-like protein 3 (SLC44A3).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Choline transporter-like protein 3 (SLC44A3).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Choline transporter-like protein 3 (SLC44A3).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Choline transporter-like protein 3 (SLC44A3).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Choline transporter-like protein 3 (SLC44A3).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Choline transporter-like protein 3 (SLC44A3).	[7]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Choline transporter-like protein 3 (SLC44A3).	[8]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Choline transporter-like protein 3 (SLC44A3).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Choline transporter-like protein 3 (SLC44A3).	[10]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Choline transporter-like protein 3 (SLC44A3).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Choline transporter-like protein 3 (SLC44A3).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Choline transporter-like protein 3 (SLC44A3).	[14]

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 Choline transporter-like protein 3 (SLC44A3).	[12]

References

• [1] Resting-state functional connectivity changes due to acute and short-term valproic acid administration in the baboon model of GGE.Neuroimage Clin. 2017 Jul 24;16:132-141. doi: 10.1016/j.nicl.2017.07.013. eCollection 2017.
• [2] 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.
• [3] 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.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [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] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [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] 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.
• [14] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.