Details of Drug Off-Target (DOT)

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

• DOT Name: Beta-1-syntrophin (SNTB1)
• Synonyms: 59 kDa dystrophin-associated protein A1 basic component 1; DAPA1B; BSYN2; Syntrophin-2; Tax interaction protein 43; TIP-43
• Gene Name: SNTB1
• Related Disease:
  Oral cancer
  Hereditary spastic paraplegia 10
  Muscular dystrophy
  Myopia
• UniProt ID: SNTB1_HUMAN
• PDB ID: 7P70; 7PC4
• Pfam ID: PF00595 ; PF00169 ; PF18012
• Sequence:
  MAVAAAAAAAGPAGAGGGRAQRSGLLEVLVRDRWHKVLVNLSEDALVLSSEEGAAAYNGI
  GTATNGSFCRGAGAGHPGAGGAQPPDSPAGVRTAFTDLPEQVPESISNQKRGVKVLKQEL
  GGLGISIKGGKENKMPILISKIFKGLAADQTQALYVGDAILSVNGADLRDATHDEAVQAL
  KRAGKEVLLEVKYMREATPYVKKGSPVSEIGWETPPPESPRLGGSTSDPPSSQSFSFHRD
  RKSIPLKMCYVTRSMALADPENRQLEIHSPDAKHTVILRSKDSATAQAWFSAIHSNVNDL
  LTRVIAEVREQLGKTGIAGSREIRHLGWLAEKVPGESKKQWKPALVVLTEKDLLIYDSMP
  RRKEAWFSPVHTYPLLATRLVHSGPGKGSPQAGVDLSFATRTGTRQGIETHLFRAETSRD
  LSHWTRSIVQGCHNSAELIAEISTACTYKNQECRLTIHYENGFSITTEPQEGAFPKTIIQ
  SPYEKLKMSSDDGIRMLYLDFGGKDGEIQLDLHSCPKPIVFIIHSFLSAKITRLGLVA
• Function: Adapter protein that binds to and probably organizes the subcellular localization of a variety of membrane proteins. May link various receptors to the actin cytoskeleton and the dystrophin glycoprotein complex.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway:
  Cytoskeleton in muscle cells (hsa04820)
  Hypertrophic cardiomyopathy (hsa05410)
  Arrhythmogenic right ventricular cardiomyopathy (hsa05412)
  Dilated cardiomyopathy (hsa05414)
  Viral myocarditis (hsa05416)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Oral cancer	DISLD42D	Definitive	Genetic Variation	[1]
Hereditary spastic paraplegia 10	DISYFO3L	Strong	Biomarker	[2]
Muscular dystrophy	DISJD6P7	Strong	Genetic Variation	[3]
Myopia	DISK5S60	Strong	Altered Expression	[4]

19 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 Beta-1-syntrophin (SNTB1).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Beta-1-syntrophin (SNTB1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Beta-1-syntrophin (SNTB1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Beta-1-syntrophin (SNTB1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Beta-1-syntrophin (SNTB1).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Beta-1-syntrophin (SNTB1).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Beta-1-syntrophin (SNTB1).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Beta-1-syntrophin (SNTB1).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Beta-1-syntrophin (SNTB1).	[14]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Beta-1-syntrophin (SNTB1).	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Beta-1-syntrophin (SNTB1).	[16]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Beta-1-syntrophin (SNTB1).	[17]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Beta-1-syntrophin (SNTB1).	[18]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Beta-1-syntrophin (SNTB1).	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Beta-1-syntrophin (SNTB1).	[22]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Beta-1-syntrophin (SNTB1).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Beta-1-syntrophin (SNTB1).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Beta-1-syntrophin (SNTB1).	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Beta-1-syntrophin (SNTB1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Beta-1-syntrophin (SNTB1).	[11]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Beta-1-syntrophin (SNTB1).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Beta-1-syntrophin (SNTB1).	[21]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Beta-1-syntrophin (SNTB1).	[25]

References

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• [2] Brazilian family with pure autosomal dominant spastic paraplegia maps to 8q: analysis of muscle beta 1 syntrophin.Am J Med Genet. 2000 May 15;92(2):122-7. doi: 10.1002/(sici)1096-8628(20000515)92:2<122::aid-ajmg8>3.0.co;2-b.
• [3] Analyses of beta-1 syntrophin, syndecan 2 and gem GTPase as candidates for chicken muscular dystrophy.Exp Anim. 2003 Oct;52(5):391-6. doi: 10.1538/expanim.52.391.
• [4] A genome-wide meta-analysis identifies two novel loci associated with high myopia in the Han Chinese population.Hum Mol Genet. 2013 Jun 1;22(11):2325-33. doi: 10.1093/hmg/ddt066. Epub 2013 Feb 12.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
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• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [12] 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.
• [13] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
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• [15] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [16] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [17] 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.
• [18] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [19] 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.
• [20] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [21] 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.
• [22] 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.
• [23] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [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] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [26] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.