Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXB60L7)

• DOT Name: Long-chain fatty acid transport protein 3 (SLC27A3)
• Synonyms: FATP-3; Fatty acid transport protein 3; Arachidonate--CoA ligase; EC 6.2.1.15; Long-chain-fatty-acid--CoA ligase; EC 6.2.1.3; Solute carrier family 27 member 3; Very long-chain acyl-CoA synthetase homolog 3; VLCS-3; EC 6.2.1.-
• Gene Name: SLC27A3
• UniProt ID: S27A3_HUMAN
• EC Number: 6.2.1.-; 6.2.1.15; 6.2.1.3
• Pfam ID: PF00501 ; PF13193
• Sequence:
  MAALLLLPLLLLLPLLLLKLHLWPQLRWLPADLAFAVRALCCKRALRARALAAAAADPEG
  PEGGCSLAWRLAELAQQRAAHTFLIHGSRRFSYSEAERESNRAARAFLRALGWDWGPDGG
  DSGEGSAGEGERAAPGAGDAAAGSGAEFAGGDGAARGGGAAAPLSPGATVALLLPAGPEF
  LWLWFGLAKAGLRTAFVPTALRRGPLLHCLRSCGARALVLAPEFLESLEPDLPALRAMGL
  HLWAAGPGTHPAGISDLLAEVSAEVDGPVPGYLSSPQSITDTCLYIFTSGTTGLPKAARI
  SHLKILQCQGFYQLCGVHQEDVIYLALPLYHMSGSLLGIVGCMGIGATVVLKSKFSAGQF
  WEDCQQHRVTVFQYIGELCRYLVNQPPSKAERGHKVRLAVGSGLRPDTWERFVRRFGPLQ
  VLETYGLTEGNVATINYTGQRGAVGRASWLYKHIFPFSLIRYDVTTGEPIRDPQGHCMAT
  SPGEPGLLVAPVSQQSPFLGYAGGPELAQGKLLKDVFRPGDVFFNTGDLLVCDDQGFLRF
  HDRTGDTFRWKGENVATTEVAEVFEALDFLQEVNVYGVTVPGHEGRAGMAALVLRPPHAL
  DLMQLYTHVSENLPPYARPRFLRLQESLATTETFKQQKVRMANEGFDPSTLSDPLYVLDQ
  AVGAYLPLTTARYSALLAGNLRI
• Function: Mainly functions as an acyl-CoA ligase catalyzing the ATP-dependent formation of fatty acyl-CoA using LCFA and very-long-chain fatty acids (VLCFA) as substrates. Can mediate the levels of long-chain fatty acids (LCFA) in the cell by facilitating their transport across membranes.
• Tissue Specificity: Expressed in bronchial and bronchiolar epithelial cells (at protein level).
• KEGG Pathway: Insulin resistance (hsa04931)
• Reactome Pathway: Synthesis of very long-chain fatty acyl-CoAs (R-HSA-75876)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Long-chain fatty acid transport protein 3 (SLC27A3) affects the response to substance of Etoposide.	[20]
Mitomycin	DMH0ZJE	Approved	Long-chain fatty acid transport protein 3 (SLC27A3) affects the response to substance of Mitomycin.	[20]

18 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 Long-chain fatty acid transport protein 3 (SLC27A3).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Long-chain fatty acid transport protein 3 (SLC27A3).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Long-chain fatty acid transport protein 3 (SLC27A3).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Long-chain fatty acid transport protein 3 (SLC27A3).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Long-chain fatty acid transport protein 3 (SLC27A3).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Long-chain fatty acid transport protein 3 (SLC27A3).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Long-chain fatty acid transport protein 3 (SLC27A3).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Long-chain fatty acid transport protein 3 (SLC27A3).	[8]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Long-chain fatty acid transport protein 3 (SLC27A3).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Long-chain fatty acid transport protein 3 (SLC27A3).	[10]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Long-chain fatty acid transport protein 3 (SLC27A3).	[11]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Long-chain fatty acid transport protein 3 (SLC27A3).	[12]
Rifampicin	DM5DSFZ	Approved	Rifampicin decreases the expression of Long-chain fatty acid transport protein 3 (SLC27A3).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Long-chain fatty acid transport protein 3 (SLC27A3).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Long-chain fatty acid transport protein 3 (SLC27A3).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Long-chain fatty acid transport protein 3 (SLC27A3).	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Long-chain fatty acid transport protein 3 (SLC27A3).	[18]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Long-chain fatty acid transport protein 3 (SLC27A3).	[19]

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 Long-chain fatty acid transport protein 3 (SLC27A3).	[15]

References

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• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] 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.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [11] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [12] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [13] Rifampin Regulation of Drug Transporters Gene Expression and the Association of MicroRNAs in Human Hepatocytes. Front Pharmacol. 2016 Apr 26;7:111.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] 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.
• [16] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [17] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [18] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [19] CD34+ derived macrophage and dendritic cells display differential responses to paraquat. Toxicol In Vitro. 2021 Sep;75:105198. doi: 10.1016/j.tiv.2021.105198. Epub 2021 Jun 9.
• [20] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.