Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYG1G80)

• DOT Name: Single-stranded DNA-binding protein 2 (SSBP2)
• Synonyms: Sequence-specific single-stranded-DNA-binding protein 2
• Gene Name: SSBP2
• Related Disease:
  Acute lymphocytic leukaemia
  Adult glioblastoma
  Advanced cancer
  B-cell lymphoma
  Benign prostatic hyperplasia
  Bipolar depression
  Bipolar disorder
  Esophageal squamous cell carcinoma
  Gallbladder cancer
  Gallbladder carcinoma
  Glioblastoma multiforme
  Neoplasm
  Prostate carcinoma
  Acute myelogenous leukaemia
  Cholecystitis
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Prostate cancer
  Prostate neoplasm
• UniProt ID: SSBP2_HUMAN
• PDB ID: 6IWV; 6TYD; 8HIB
• Pfam ID: PF04503
• Sequence:
  MYGKGKSNSSAVPSDSQAREKLALYVYEYLLHVGAQKSAQTFLSEIRWEKNITLGEPPGF
  LHSWWCVFWDLYCAAPERRETCEHSSEAKAFHDYSAAAAPSPVLGNIPPGDGMPVGPVPP
  GFFQPFMSPRYPGGPRPPLRIPNQALGGVPGSQPLLPSGMDPTRQQGHPNMGGPMQRMTP
  PRGMVPLGPQNYGGAMRPPLNALGGPGMPGMNMGPGGGRPWPNPTNANSIPYSSASPGNY
  VGPPGGGGPPGTPIMPSPADSTNSGDNMYTLMNAVPPGPNRPNFPMGPGSDGPMGGLGGM
  ESHHMNGSLGSGDMDSISKNSPNNMSLSNQPGTPRDDGEMGGNFLNPFQSESYSPSMTMS
  V
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute lymphocytic leukaemia	DISPX75S	Strong	Genetic Variation	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Posttranslational Modification	[2]
B-cell lymphoma	DISIH1YQ	Strong	Altered Expression	[3]
Benign prostatic hyperplasia	DISI3CW2	Strong	Genetic Variation	[4]
Bipolar depression	DISA75FU	Strong	Biomarker	[5]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[5]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[6]
Gallbladder cancer	DISXJUAF	Strong	Posttranslational Modification	[2]
Gallbladder carcinoma	DISD6ACL	Strong	Posttranslational Modification	[2]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[4]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[8]
Cholecystitis	DISG024R	Limited	Posttranslational Modification	[9]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[2]
leukaemia	DISS7D1V	Limited	Biomarker	[8]
Leukemia	DISNAKFL	Limited	Biomarker	[8]
Prostate cancer	DISF190Y	Limited	Altered Expression	[4]
Prostate neoplasm	DISHDKGQ	Limited	Biomarker	[4]

20 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 Single-stranded DNA-binding protein 2 (SSBP2).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Single-stranded DNA-binding protein 2 (SSBP2).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Single-stranded DNA-binding protein 2 (SSBP2).	[12]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Single-stranded DNA-binding protein 2 (SSBP2).	[13]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Single-stranded DNA-binding protein 2 (SSBP2).	[14]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Single-stranded DNA-binding protein 2 (SSBP2).	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Single-stranded DNA-binding protein 2 (SSBP2).	[16]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Single-stranded DNA-binding protein 2 (SSBP2).	[17]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Single-stranded DNA-binding protein 2 (SSBP2).	[18]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Single-stranded DNA-binding protein 2 (SSBP2).	[13]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Single-stranded DNA-binding protein 2 (SSBP2).	[13]
Mestranol	DMG3F94	Approved	Mestranol decreases the expression of Single-stranded DNA-binding protein 2 (SSBP2).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Single-stranded DNA-binding protein 2 (SSBP2).	[18]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Single-stranded DNA-binding protein 2 (SSBP2).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Single-stranded DNA-binding protein 2 (SSBP2).	[19]
HEXESTROL	DM9AGWQ	Withdrawn from market	HEXESTROL decreases the expression of Single-stranded DNA-binding protein 2 (SSBP2).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Single-stranded DNA-binding protein 2 (SSBP2).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Single-stranded DNA-binding protein 2 (SSBP2).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Single-stranded DNA-binding protein 2 (SSBP2).	[21]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Single-stranded DNA-binding protein 2 (SSBP2).	[22]

References

• [1] Novel SSBP2-JAK2 fusion gene resulting from a t(5;9)(q14.1;p24.1) in pre-B acute lymphocytic leukemia.Genes Chromosomes Cancer. 2008 Oct;47(10):884-9. doi: 10.1002/gcc.20585.
• [2] Single-stranded DNA binding protein 2 expression is associated with patient survival in hepatocellular carcinoma.BMC Cancer. 2018 Dec 12;18(1):1244. doi: 10.1186/s12885-018-5158-z.
• [3] Clinical and biological significance of de novo CD5+ diffuse large B-cell lymphoma in Western countries.Oncotarget. 2015 Mar 20;6(8):5615-33. doi: 10.18632/oncotarget.3479.
• [4] ssDNA-binding protein 2 is frequently hypermethylated and suppresses cell growth in human prostate cancer.Clin Cancer Res. 2008 Jun 15;14(12):3754-60. doi: 10.1158/1078-0432.CCR-07-4763.
• [5] Genome-wide association study identifies 30 loci associated with bipolar disorder.Nat Genet. 2019 May;51(5):793-803. doi: 10.1038/s41588-019-0397-8. Epub 2019 May 1.
• [6] Cigarette smoke induces promoter methylation of single-stranded DNA-binding protein 2 in human esophageal squamous cell carcinoma.Int J Cancer. 2011 May 15;128(10):2261-73. doi: 10.1002/ijc.25569.
• [7] Crystal structure of the LUFS domain of human single-stranded DNA binding Protein 2 (SSBP2).Protein Sci. 2019 Apr;28(4):788-793. doi: 10.1002/pro.3581. Epub 2019 Feb 12.
• [8] Adenoviral E1B55K oncoprotein sequesters candidate leukemia suppressor sequence-specific single-stranded DNA-binding protein 2 into aggresomes.Oncogene. 2007 Jul 19;26(33):4797-805. doi: 10.1038/sj.onc.1210281. Epub 2007 Feb 19.
• [9] Global and gene-specific DNA methylation pattern discriminates cholecystitis from gallbladder cancer patients in Chile.Future Oncol. 2015;11(2):233-49. doi: 10.2217/fon.14.165. Epub 2014 Jul 28.
• [10] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [11] 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.
• [12] 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.
• [13] Moving toward integrating gene expression profiling into high-throughput testing: a gene expression biomarker accurately predicts estrogen receptor alpha modulation in a microarray compendium. Toxicol Sci. 2016 May;151(1):88-103.
• [14] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [15] 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.
• [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] 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.
• [18] 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.
• [19] 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.
• [20] Evaluation of estrogen receptor alpha activation by glyphosate-based herbicide constituents. Food Chem Toxicol. 2017 Oct;108(Pt A):30-42.
• [21] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [22] 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.