Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9EVUN1)

• DOT Name: MFS-type transporter SLC18B1 (SLC18B1)
• Synonyms: Solute carrier family 18 member B1; Vesicular polyamine transporter; VPAT
• Gene Name: SLC18B1
• UniProt ID: S18B1_HUMAN
• Pfam ID: PF07690
• Sequence:
  MEALGDLEGPRAPGGDDPAGSAGETPGWLSREQVFVLISAASVNLGSMMCYSILGPFFPK
  EAEKKGASNTIIGMIFGCFALFELLASLVFGNYLVHIGAKFMFVAGMFVSGGVTILFGVL
  DRVPDGPVFIAMCFLVRVMDAVSFAAAMTASSSILAKAFPNNVATVLGSLETFSGLGLIL
  GPPVGGFLYQSFGYEVPFIVLGCVVLLMVPLNMYILPNYESDPGEHSFWKLIALPKVGLI
  AFVINSLSSCFGFLDPTLSLFVLEKFNLPAGYVGLVFLGMALSYAISSPLFGLLSDKRPP
  LRKWLLVFGNLITAGCYMLLGPVPILHIKSQLWLLVLILVVSGLSAGMSIIPTFPEILSC
  AHENGFEEGLSTLGLVSGLFSAMWSIGAFMGPTLGGFLYEKIGFEWAAAIQGLWALISGL
  AMGLFYLLEYSRRKRSKSQNILSTEEERTTLLPNET
• Function: Proton-coupled polyamine antiporter involved in the translocation of polyamines from cytosol into secretory vesicles prior to their release via exocytosis. Uses the electrochemical proton gradient generated by a V-type proton-pumping ATPase to couple the efflux of protons with the uptake of a polyamine molecule. Facilitates vesicular storage of spermine and spermidine in astrocytes with an impact on glutamatergic neuronal transmission and memory formation. Upon antigen stimulation, regulates polyamine accumulation and release in mast cell secretory granules, which in turn potentiates mast cell degranulation and histamine secretion.
• Tissue Specificity: Expressed in various tissues including lung, placenta, adrenal gland, liver, testis, and brain.

Molecular Interaction Atlas (MIA) of This DOT

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 MFS-type transporter SLC18B1 (SLC18B1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of MFS-type transporter SLC18B1 (SLC18B1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of MFS-type transporter SLC18B1 (SLC18B1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of MFS-type transporter SLC18B1 (SLC18B1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of MFS-type transporter SLC18B1 (SLC18B1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of MFS-type transporter SLC18B1 (SLC18B1).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of MFS-type transporter SLC18B1 (SLC18B1).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of MFS-type transporter SLC18B1 (SLC18B1).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of MFS-type transporter SLC18B1 (SLC18B1).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of MFS-type transporter SLC18B1 (SLC18B1).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of MFS-type transporter SLC18B1 (SLC18B1).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of MFS-type transporter SLC18B1 (SLC18B1).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of MFS-type transporter SLC18B1 (SLC18B1).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of MFS-type transporter SLC18B1 (SLC18B1).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of MFS-type transporter SLC18B1 (SLC18B1).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of MFS-type transporter SLC18B1 (SLC18B1).	[13]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of MFS-type transporter SLC18B1 (SLC18B1).	[14]
AM251	DMTAWHL	Investigative	AM251 decreases the expression of MFS-type transporter SLC18B1 (SLC18B1).	[15]

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] 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.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [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] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [13] 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.
• [14] 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.
• [15] Cannabinoid derivatives induce cell death in pancreatic MIA PaCa-2 cells via a receptor-independent mechanism. FEBS Lett. 2006 Mar 20;580(7):1733-9.