Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF1DT72)

• DOT Name: Sugar transporter SWEET1 (SLC50A1)
• Synonyms: HsSWEET1; RAG1-activating protein 1; Solute carrier family 50 member 1; Stromal cell protein
• Gene Name: SLC50A1
• UniProt ID: SWET1_HUMAN
• Pfam ID: PF03083
• Sequence:
  MEAGGFLDSLIYGACVVFTLGMFSAGLSDLRHMRMTRSVDNVQFLPFLTTEVNNLGWLSY
  GALKGDGILIVVNTVGAALQTLYILAYLHYCPRKRVVLLQTATLLGVLLLGYGYFWLLVP
  NPEARLQQLGLFCSVFTISMYLSPLADLAKVIQTKSTQCLSYPLTIATLLTSASWCLYGF
  RLRDPYIMVSNFPGIVTSFIRFWLFWKYPQEQDRNYWLLQT
• Function: Mediates sugar transport across membranes. May stimulate V(D)J recombination by the activation of RAG1.
• Tissue Specificity: Ubiquitously expressed with highest expression in oviduct, epididymis and intestine.
• Reactome Pathway: Cellular hexose transport (R-HSA-189200)

Molecular Interaction Atlas (MIA) of This DOT

1 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 Sugar transporter SWEET1 (SLC50A1).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Sugar transporter SWEET1 (SLC50A1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sugar transporter SWEET1 (SLC50A1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Sugar transporter SWEET1 (SLC50A1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Sugar transporter SWEET1 (SLC50A1).	[5]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Sugar transporter SWEET1 (SLC50A1).	[6]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Sugar transporter SWEET1 (SLC50A1).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Sugar transporter SWEET1 (SLC50A1).	[8]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Sugar transporter SWEET1 (SLC50A1).	[9]

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] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [7] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [8] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [9] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.