Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOXI54L)

• DOT Name: Sodium/bile acid cotransporter 4 (SLC10A4)
• Synonyms: Na(+)/bile acid cotransporter 4; Solute carrier family 10 member 4
• Gene Name: SLC10A4
• UniProt ID: NTCP4_HUMAN
• Pfam ID: PF01758
• Sequence:
  MDGNDNVTLLFAPLLRDNYTLAPNASSLGPGTDLALAPASSAGPGPGLSLGPGPSFGFSP
  GPTPTPEPTTSGLAGGAASHGPSPFPRPWAPHALPFWDTPLNHGLNVFVGAALCITMLGL
  GCTVDVNHFGAHVRRPVGALLAALCQFGLLPLLAFLLALAFKLDEVAAVAVLLCGCCPGG
  NLSNLMSLLVDGDMNLSIIMTISSTLLALVLMPLCLWIYSWAWINTPIVQLLPLGTVTLT
  LCSTLIPIGLGVFIRYKYSRVADYIVKVSLWSLLVTLVVLFIMTGTMLGPELLASIPAAV
  YVIAIFMPLAGYASGYGLATLFHLPPNCKRTVCLETGSQNVQLCTAILKLAFPPQFIGSM
  YMFPLLYALFQSAEAGIFVLIYKMYGSEMLHKRDPLDEDEDTDISYKKLKEEEMADTSYG
  TVKAENIIMMETAQTSL
• Function: Transporter for bile acids.
• Tissue Specificity: Highly expressed in brain and small intestine, and moderately expressed in colon, heart, prostate, and testis. Very low levels were detected in kidney, liver, ovary, placenta, spleen, and thymus.

Molecular Interaction Atlas (MIA) of This DOT

3 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 Sodium/bile acid cotransporter 4 (SLC10A4).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Sodium/bile acid cotransporter 4 (SLC10A4).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sodium/bile acid cotransporter 4 (SLC10A4).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Sodium/bile acid cotransporter 4 (SLC10A4).	[2]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Sodium/bile acid cotransporter 4 (SLC10A4).	[4]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Sodium/bile acid cotransporter 4 (SLC10A4).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Sodium/bile acid cotransporter 4 (SLC10A4).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Sodium/bile acid cotransporter 4 (SLC10A4).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Sodium/bile acid cotransporter 4 (SLC10A4).	[9]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Sodium/bile acid cotransporter 4 (SLC10A4).	[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] 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.
• [3] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.