Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP7EAUM)

• DOT Name: Solute carrier family 25 member 45 (SLC25A45)
• Gene Name: SLC25A45
• Related Disease:
  Clear cell adenocarcinoma
  Epithelial ovarian cancer
  Pancreatic cancer
  Melanoma
• UniProt ID: S2545_HUMAN
• Pfam ID: PF00153
• Sequence:
  MPVEEFVAGWISGALGLVLGHPFDTVKVRLQTQTTYRGIVDCMVKIYRHESLLGFFKGMS
  FPIASIAVVNSVLFGVYSNTLLVLTATSHQERRAQPPSYMHIFLAGCTGGFLQAYCLAPF
  DLIKVRLQNQTEPRAQPGSPPPRYQGPVHCAASIFREEGPRGLFRGAWALTLRDTPTVGI
  YFITYEGLCRQYTPEGQNPSSATVLVAGGFAGIASWVAATPLDMIKSRMQMDGLRRRVYQ
  GMLDCMVSSIRQEGLGVFFRGVTINSARAFPVNAVTFLSYEYLLRWWG

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Clear cell adenocarcinoma	DISYUGHZ	Definitive	Biomarker	[1]
Epithelial ovarian cancer	DIS56MH2	Definitive	Genetic Variation	[1]
Pancreatic cancer	DISJC981	moderate	Biomarker	[2]
Melanoma	DIS1RRCY	Limited	Biomarker	[3]

12 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 Solute carrier family 25 member 45 (SLC25A45).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Solute carrier family 25 member 45 (SLC25A45).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Solute carrier family 25 member 45 (SLC25A45).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Solute carrier family 25 member 45 (SLC25A45).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Solute carrier family 25 member 45 (SLC25A45).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Solute carrier family 25 member 45 (SLC25A45).	[9]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Solute carrier family 25 member 45 (SLC25A45).	[10]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Solute carrier family 25 member 45 (SLC25A45).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Solute carrier family 25 member 45 (SLC25A45).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Solute carrier family 25 member 45 (SLC25A45).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Solute carrier family 25 member 45 (SLC25A45).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Solute carrier family 25 member 45 (SLC25A45).	[16]

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 decreases the methylation of Solute carrier family 25 member 45 (SLC25A45).	[15]

References

• [1] Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk.PLoS One. 2015 Jun 19;10(6):e0128106. doi: 10.1371/journal.pone.0128106. eCollection 2015.
• [2] Identification of a Nine-Gene Signature and Establishment of a Prognostic Nomogram Predicting Overall Survival of Pancreatic Cancer.Front Oncol. 2019 Sep 27;9:996. doi: 10.3389/fonc.2019.00996. eCollection 2019.
• [3] Aggressiveness of human melanoma xenograft models is promoted by aneuploidy-driven gene expression deregulation.Oncotarget. 2012 Apr;3(4):399-413. doi: 10.18632/oncotarget.473.
• [4] 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.
• [5] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [6] 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.
• [7] 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.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] 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.
• [10] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [11] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [12] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.