Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY6MWVD)

• DOT Name: Solute carrier family 25 member 43 (SLC25A43)
• Gene Name: SLC25A43
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  HER2/NEU overexpressing breast cancer
  Neoplasm
  Bone Paget disease
  Paget's disease
• UniProt ID: S2543_HUMAN
• Pfam ID: PF00153
• Sequence:
  MATWRRDGRLTGGQRLLCAGLAGTLSLSLTAPLELATVLAQVGVVRGHARGPWATGHRVW
  RAEGLRALWKGNAVACLRLFPCSAVQLAAYRKFVVLFTDDLGHISQWSSIMAGSLAGMVS
  TIVTYPTDLIKTRLIMQNILEPSYRGLLHAFSTIYQQEGFLALYRGVSLTVVGALPFSAG
  SLLVYMNLEKIWNGPRDQFSLPQNFANVCLAAAVTQTLSFPFETVKRKMQAQSPYLPHSG
  GVDVHFSGAVDCFRQIVKAQGVLGLWNGLTANLLKIVPYFGIMFSTFEFCKRICLYQNGY
  ILSPLSYKLTPGVDQSLQPQELRELKKFFKTRKPKPKKPTL

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Breast neoplasm	DISNGJLM	Strong	Genetic Variation	[3]
Carcinoma	DISH9F1N	Strong	Altered Expression	[2]
HER2/NEU overexpressing breast cancer	DISYKID5	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[3]
Bone Paget disease	DISIPS4V	moderate	Genetic Variation	[4]
Paget's disease	DISO3MC0	moderate	Genetic Variation	[4]

12 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 Solute carrier family 25 member 43 (SLC25A43).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Solute carrier family 25 member 43 (SLC25A43).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Solute carrier family 25 member 43 (SLC25A43).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Solute carrier family 25 member 43 (SLC25A43).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Solute carrier family 25 member 43 (SLC25A43).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Solute carrier family 25 member 43 (SLC25A43).	[10]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Solute carrier family 25 member 43 (SLC25A43).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Solute carrier family 25 member 43 (SLC25A43).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Solute carrier family 25 member 43 (SLC25A43).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Solute carrier family 25 member 43 (SLC25A43).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Solute carrier family 25 member 43 (SLC25A43).	[5]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Solute carrier family 25 member 43 (SLC25A43).	[16]

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 decreases the methylation of Solute carrier family 25 member 43 (SLC25A43).	[13]

References

• [1] The mitochondrial transport protein SLC25A43 affects drug efficacy and drug-induced cell cycle arrest in breast cancer cell lines.Oncol Rep. 2013 Apr;29(4):1268-74. doi: 10.3892/or.2013.2247. Epub 2013 Jan 23.
• [2] Decreased expression of the mitochondrial solute carrier SLC25A43 in basal cell carcinoma compared with healthy skin.Oncol Lett. 2017 Aug;14(2):2218-2222. doi: 10.3892/ol.2017.6452. Epub 2017 Jun 21.
• [3] DNA methylation pattern of the SLC25A43 gene in breast cancer.Epigenetics. 2012 Mar;7(3):300-6. doi: 10.4161/epi.7.3.19064.
• [4] Genome-wide association identifies three new susceptibility loci for Paget's disease of bone.Nat Genet. 2011 May 29;43(7):685-9. doi: 10.1038/ng.845.
• [5] 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.
• [6] 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.
• [7] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] 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.
• [11] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] 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.
• [14] Highly active combination of BRD4 antagonist and histone deacetylase inhibitor against human acute myelogenous leukemia cells. Mol Cancer Ther. 2014 May;13(5):1142-54.
• [15] 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.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.