Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTLD0KB)

• DOT Name: Sulfide:quinone oxidoreductase, mitochondrial (SQOR)
• Synonyms: SQOR; EC 1.8.5.8; Sulfide dehydrogenase-like; Sulfide quinone oxidoreductase
• Gene Name: SQOR
• Related Disease:
  Depression
  Kidney failure
  Nephrotic syndrome
  Sulfide quinone oxidoreductase deficiency
  Coenzyme Q10 deficiency
  Leigh syndrome
  Osteoporosis
  Postmenopausal osteoporosis
• UniProt ID: SQOR_HUMAN
• PDB ID: 6MO6; 6MP5; 6OI5; 6OI6; 6OIB; 6OIC; 6WH6; 8DHK
• EC Number: 1.8.5.8
• Pfam ID: PF07992
• Sequence:
  MVPLVAVVSGPRAQLFACLLRLGTQQVGPLQLHTGASHAARNHYEVLVLGGGSGGITMAA
  RMKRKVGAENVAIVEPSERHFYQPIWTLVGAGAKQLSSSGRPTASVIPSGVEWIKARVTE
  LNPDKNCIHTDDDEKISYRYLIIALGIQLDYEKIKGLPEGFAHPKIGSNYSVKTVEKTWK
  ALQDFKEGNAIFTFPNTPVKCAGAPQKIMYLSEAYFRKTGKRSKANIIFNTSLGAIFGVK
  KYADALQEIIQERNLTVNYKKNLIEVRADKQEAVFENLDKPGETQVISYEMLHVTPPMSP
  PDVLKTSPVADAAGWVDVDKETLQHRRYPNVFGIGDCTNLPTSKTAAAVAAQSGILDRTI
  SVIMKNQTPTKKYDGYTSCPLVTGYNRVILAEFDYKAEPLETFPFDQSKERLSMYLMKAD
  LMPFLYWNMMLRGYWGGPAFLRKLFHLGMS
• Function: Catalyzes the oxidation of hydrogen sulfide with the help of a quinone, such as ubiquinone-10, giving rise to thiosulfate and ultimately to sulfane (molecular sulfur) atoms. Requires an additional electron acceptor; can use sulfite, sulfide or cyanide (in vitro). It is believed the in vivo electron acceptor is glutathione.
• KEGG Pathway:
  Sulfur metabolism (hsa00920)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Sulfide oxidation to sulfate (R-HSA-1614517)
• BioCyc Pathway: MetaCyc:HS06393-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Depression	DIS3XJ69	Strong	Biomarker	[1]
Kidney failure	DISOVQ9P	Strong	Altered Expression	[2]
Nephrotic syndrome	DISSPSC2	Strong	Altered Expression	[2]
Sulfide quinone oxidoreductase deficiency	DISIO175	Strong	Autosomal recessive	[3]
Coenzyme Q10 deficiency	DIS1HGDF	Disputed	Altered Expression	[2]
Leigh syndrome	DISWQU45	Limited	Autosomal recessive	[4]
Osteoporosis	DISF2JE0	Limited	Biomarker	[5]
Postmenopausal osteoporosis	DISS0RQZ	Limited	Biomarker	[5]

22 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 Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[12]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[13]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[14]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[15]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[16]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[17]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[18]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[19]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[20]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[21]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[21]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[25]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[26]

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 Sulfide:quinone oxidoreductase, mitochondrial (SQOR).	[22]

References

• [1] X-Ray Structure of Human Sulfide:Quinone Oxidoreductase: Insights into the Mechanism of Mitochondrial Hydrogen Sulfide Oxidation.Structure. 2019 May 7;27(5):794-805.e4. doi: 10.1016/j.str.2019.03.002. Epub 2019 Mar 21.
• [2] CoQ(10) supplementation rescues nephrotic syndrome through normalization of H(2)S oxidation pathway.Biochim Biophys Acta Mol Basis Dis. 2018 Nov;1864(11):3708-3722. doi: 10.1016/j.bbadis.2018.09.002. Epub 2018 Sep 6.
• [3] Pathogenic variants in SQOR encoding sulfide:quinone oxidoreductase are a potentially treatable cause of Leigh disease. J Inherit Metab Dis. 2020 Sep;43(5):1024-1036. doi: 10.1002/jimd.12232. Epub 2020 Apr 15.
• [4] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [5] Genetic susceptibility of postmenopausal osteoporosis on sulfide quinone reductase-like gene.Osteoporos Int. 2018 Sep;29(9):2041-2047. doi: 10.1007/s00198-018-4575-9. Epub 2018 May 31.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [17] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [18] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [19] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [20] 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.
• [21] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [22] 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.
• [23] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [24] 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.
• [25] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [26] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.