Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEJN38N)

• DOT Name: Sodium/potassium/calcium exchanger 3 (SLC24A3)
• Synonyms: Na(+)/K(+)/Ca(2+)-exchange protein 3; Solute carrier family 24 member 3
• Gene Name: SLC24A3
• UniProt ID: NCKX3_HUMAN
• Pfam ID: PF01699
• Sequence:
  MRPSGDEDRARRRRRRRRRRDLLLSQLCFLASVALLLWSLSSLREQKELDLMDLVGEDRK
  WMMARKLMQVNDTLTSEDAGLRNSKNCTEPALHEFPNDIFTNEDRRQGAVVLHVLCAIYM
  FYALAIVCDDFFVPSLEKICERLHLSEDVAGATFMAAGSSAPELFTSVIGVFITKGDVGV
  GTIVGSAVFNILCIIGVCGLFAGQVVALSSWCLLRDSIYYTLSVIALIVFIYDEKVSWWE
  SLVLVLMYLIYIVIMKYNACIHQCFERRTKGAGNMVNGLANNAEIDDSSNCDATVVLLKK
  ANFHRKASVIMVDELLSAYPHQLSFSEAGLRIMITSHFPPKTRLSMASRMLINERQRLIN
  SRAYTNGESEVAIKIPIKHTVENGTGPSSAPDRGVNGTRRDDVVAEAGNETENENEDNEN
  DEEEEEDEDDDEGPYTPFDTPSGKLETVKWAFTWPLSFVLYFTVPNCNKPRWEKWFMVTF
  ASSTLWIAAFSYMMVWMVTIIGYTLGIPDVIMGITFLAAGTSVPDCMASLIVARQGMGDM
  AVSNSIGSNVFDILIGLGLPWALQTLAVDYGSYIRLNSRGLIYSVGLLLASVFVTVFGVH
  LNKWQLDKKLGCGCLLLYGVFLCFSIMTEFNVFTFVNLPMCGDH
• Function: Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) in exchange for 4 Na(+).
• Tissue Specificity: Abundant in the brain . Expressed at low levels in the aorta, uterus and intestine .
• Reactome Pathway: Sodium/Calcium exchangers (R-HSA-425561)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Sodium/potassium/calcium exchanger 3 (SLC24A3).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Sodium/potassium/calcium exchanger 3 (SLC24A3).	[2]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Sodium/potassium/calcium exchanger 3 (SLC24A3).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Sodium/potassium/calcium exchanger 3 (SLC24A3).	[4]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Sodium/potassium/calcium exchanger 3 (SLC24A3).	[5]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Sodium/potassium/calcium exchanger 3 (SLC24A3).	[1]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Sodium/potassium/calcium exchanger 3 (SLC24A3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Sodium/potassium/calcium exchanger 3 (SLC24A3).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Sodium/potassium/calcium exchanger 3 (SLC24A3).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Sodium/potassium/calcium exchanger 3 (SLC24A3).	[9]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Sodium/potassium/calcium exchanger 3 (SLC24A3).	[8]

References

• [1] 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.
• [2] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [4] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [7] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.