Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2HPUAI)

• DOT Name: Stonin-1 (STON1)
• Synonyms: Stoned B-like factor
• Gene Name: STON1
• Related Disease:
  Acute leukaemia
  Acute liver failure
  Coagulation defect
  Epilepsy
  FRAXE intellectual disability
  Hepatitis B virus infection
  Hepatitis C virus infection
  Herpes simplex infection
  Neoplasm
  Wilson disease
  Adrenoleukodystrophy
  Hepatitis
• UniProt ID: STON1_HUMAN
• Pfam ID: PF00928
• Sequence:
  MCSTNPGKWVTFDDDPAVQSSQKSKNFPLENQGVCRPNGLKLNLPGLREFPSGSSSTSST
  PLSSPIVDFYFSPGPPSNSPLSTPTKDFPGFPGIPKAGTHVLYPIPESSSDSPLAISGGE
  SSLLPTRPTCLSHALLPSDHSCTHPTPKVGLPDEVNPQQAESLGFQSDDLPQFQYFREDC
  AFSSPFWKDEGSDSHFTLDPPGSKKMFSSRNKEMPIDQKSLNKCSLNYICEKLEHLQSAE
  NQDSLRSLSMHCLCAEENASSFVPHTLFRSQPKSGWSFMLRIPEKKNMMSSRQWGPIFLK
  VLPGGILQMYYEQGLEKPFKEIQLDPYCRLSEPKVENFSVAGKIHTVKIEHVSYTEKRKY
  HSKTEVVHEPDIEQMLKLGSTSYHDFLDFLTTVEEELMKLPAVSKPKKNYEEQEISLEIV
  DNFWGKVTKEGKFVESAVITQIYCLCFVNGNLECFLTLNDLELPKRDESYYEKDSEKKGI
  DILDYHFHKCVNVQEFEQSRIIKFVPLDACRFELMRFKTLYNGDNLPFSLKSVVVVQGAY
  VELQAFVNMASLAQRSSYAGSLRSCDNIRIHFPVPSQWIKALWTMNLQRQKSLKAKMNRR
  ACLGSLQELESEPVIQVTVGSAKYESAYQAVVWKIDRLPDKNSSLDHPHCLSYKLELGSD
  QEIPSDWYPFATVQFSVPDTCASRTEVRSLGVESDVQPQKHVQQRACYNIQVEIEKKWIK
  IDGEDPDKIGDCITQ
• Function: May be involved in the endocytic machinery.
• Tissue Specificity: Ubiquitous.
• Reactome Pathway:
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute leukaemia	DISDQFDI	Strong	Altered Expression	[1]
Acute liver failure	DIS5EZKX	Strong	Biomarker	[2]
Coagulation defect	DIS9X3H6	Strong	Biomarker	[3]
Epilepsy	DISBB28L	Strong	Biomarker	[4]
FRAXE intellectual disability	DISDPS6G	Strong	Genetic Variation	[1]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[5]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[6]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Wilson disease	DISVS9H7	Strong	Biomarker	[2]
Adrenoleukodystrophy	DISTUD1F	moderate	Biomarker	[9]
Hepatitis	DISXXX35	Limited	Biomarker	[10]

13 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 Stonin-1 (STON1).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Stonin-1 (STON1).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Stonin-1 (STON1).	[13]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Stonin-1 (STON1).	[14]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Stonin-1 (STON1).	[15]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Stonin-1 (STON1).	[16]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Stonin-1 (STON1).	[17]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Stonin-1 (STON1).	[18]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Stonin-1 (STON1).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Stonin-1 (STON1).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Stonin-1 (STON1).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Stonin-1 (STON1).	[23]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Stonin-1 (STON1).	[24]

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 Stonin-1 (STON1).	[20]

References

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• [2] Plasmapheresis Combined with Continuous Plasma Filtration Adsorption Rescues Severe Acute Liver Failure in Wilson's Disease before Liver Transplantation.Blood Purif. 2019;47(1-3):120-125. doi: 10.1159/000493909. Epub 2018 Oct 25.
• [3] Bleeding complications in acute liver failure.Hepatology. 2018 May;67(5):1931-1942. doi: 10.1002/hep.29694. Epub 2018 Mar 26.
• [4] Accelerated long-term forgetting and behavioural difficulties in children with epilepsy.Cortex. 2019 Jan;110:92-100. doi: 10.1016/j.cortex.2018.03.021. Epub 2018 Mar 30.
• [5] Two distinct subtypes of hepatitis B virus-related acute liver failure are separable by quantitative serum immunoglobulin M anti-hepatitis B core antibody and hepatitis B virus DNA levels.Hepatology. 2012 Mar;55(3):676-84. doi: 10.1002/hep.24732. Epub 2012 Jan 31.
• [6] Occult hepatitis C virus infection in patients in whom the etiology of persistently abnormal results of liver-function tests is unknown.J Infect Dis. 2004 Jan 1;189(1):7-14. doi: 10.1086/380202. Epub 2003 Dec 31.
• [7] Living donor liver transplantation for neonatal fulminant hepatitis due to herpes simplex virus infection.Pediatr Transplant. 2017 Nov;21(7). doi: 10.1111/petr.13021. Epub 2017 Jul 23.
• [8] Identification of a sodium pump Na(+)/K(+) ATPase 1-targeted peptide for PET imaging of breast cancer.J Control Release. 2018 Jul 10;281:178-188. doi: 10.1016/j.jconrel.2018.05.019. Epub 2018 May 17.
• [9] Pathophysiology and Management of Alcoholic Liver Disease: Update 2016.Gut Liver. 2017 Mar 15;11(2):173-188. doi: 10.5009/gnl16477.
• [10] The Role of Monocytes and Macrophages in Acute and Acute-on-Chronic Liver Failure.Front Immunol. 2018 Dec 14;9:2948. doi: 10.3389/fimmu.2018.02948. eCollection 2018.
• [11] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [12] 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.
• [13] 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.
• [14] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [15] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [16] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [17] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [18] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [19] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [20] 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.
• [21] 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.
• [22] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
• [23] 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.
• [24] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.