Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT37U4O)

• DOT Name: Neuroblastoma suppressor of tumorigenicity 1 (NBL1)
• Synonyms: DAN domain family member 1; Protein N03; Zinc finger protein DAN
• Gene Name: NBL1
• Related Disease:
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Coronary atherosclerosis
  Coronary heart disease
  Dorfman-Chanarin disease
  Lafora disease
  Neoplasm
  Non-small-cell lung cancer
  Obstructive sleep apnea
  Pancreatitis
  Bronchopulmonary dysplasia
  Metastatic melanoma
  Pancreatic cancer
  Parkinson disease
  Prostate cancer
  Prostate carcinoma
• UniProt ID: NBL1_HUMAN
• PDB ID: 4X1J; 4YU8
• Pfam ID: PF03045
• Sequence:
  MMLRVLVGAVLPAMLLAAPPPINKLALFPDKSAWCEAKNITQIVGHSGCEAKSIQNRACL
  GQCFSYSVPNTFPQSTESLVHCDSCMPAQSMWEIVTLECPGHEEVPRVDKLVEKILHCSC
  QACGKEPSHEGLSVYVQGEDGPGSQPGTHPHPHPHPHPGGQTPEPEDPPGAPHTEEEGAE
  D
• Function: Possible candidate as a tumor suppressor gene of neuroblastoma. May play an important role in preventing cells from entering the final stage (G1/S) of the transformation process.
• Tissue Specificity: Most abundant in normal lung and meningioma.
• KEGG Pathway: TGF-beta sig.ling pathway (hsa04350)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[2]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[2]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[2]
Coronary heart disease	DIS5OIP1	Strong	Altered Expression	[2]
Dorfman-Chanarin disease	DISKKT3R	Strong	Genetic Variation	[3]
Lafora disease	DIS83JHH	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[6]
Obstructive sleep apnea	DIS0SVD1	Strong	Altered Expression	[2]
Pancreatitis	DIS0IJEF	Strong	Altered Expression	[7]
Bronchopulmonary dysplasia	DISO0BY5	moderate	Genetic Variation	[8]
Metastatic melanoma	DISSL43L	Limited	Biomarker	[9]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[10]
Parkinson disease	DISQVHKL	Limited	Biomarker	[11]
Prostate cancer	DISF190Y	Limited	Altered Expression	[12]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[12]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	Neuroblastoma suppressor of tumorigenicity 1 (NBL1) affects the response to substance of DTI-015.	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Neuroblastoma suppressor of tumorigenicity 1 (NBL1).	[13]

16 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Neuroblastoma suppressor of tumorigenicity 1 (NBL1).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Neuroblastoma suppressor of tumorigenicity 1 (NBL1).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Neuroblastoma suppressor of tumorigenicity 1 (NBL1).	[16]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Neuroblastoma suppressor of tumorigenicity 1 (NBL1).	[17]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Neuroblastoma suppressor of tumorigenicity 1 (NBL1).	[18]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Neuroblastoma suppressor of tumorigenicity 1 (NBL1).	[19]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Neuroblastoma suppressor of tumorigenicity 1 (NBL1).	[19]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Neuroblastoma suppressor of tumorigenicity 1 (NBL1).	[20]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Neuroblastoma suppressor of tumorigenicity 1 (NBL1).	[21]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Neuroblastoma suppressor of tumorigenicity 1 (NBL1).	[22]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Neuroblastoma suppressor of tumorigenicity 1 (NBL1).	[23]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Neuroblastoma suppressor of tumorigenicity 1 (NBL1).	[24]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Neuroblastoma suppressor of tumorigenicity 1 (NBL1).	[25]
ACYLINE	DM9GRTK	Phase 2	ACYLINE decreases the expression of Neuroblastoma suppressor of tumorigenicity 1 (NBL1).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Neuroblastoma suppressor of tumorigenicity 1 (NBL1).	[27]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Neuroblastoma suppressor of tumorigenicity 1 (NBL1).	[28]

References

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• [2] Circulating autoantibodies against neuroblastoma suppressor of tumorigenicity 1 (NBL1): A potential biomarker for coronary artery disease in patients with obstructive sleep apnea.PLoS One. 2018 Mar 29;13(3):e0195015. doi: 10.1371/journal.pone.0195015. eCollection 2018.
• [3] Dive Risk Factors, Gas Bubble Formation, and Decompression Illness in Recreational SCUBA Diving: Analysis of DAN Europe DSL Data Base.Front Psychol. 2017 Sep 19;8:1587. doi: 10.3389/fpsyg.2017.01587. eCollection 2017.
• [4] Divergent functional connectivity during attentional processing in Lewy body dementia and Alzheimer's disease.Cortex. 2017 Jul;92:8-18. doi: 10.1016/j.cortex.2017.02.016. Epub 2017 Mar 18.
• [5] Interleukin 2 with anti-GD2 antibody ch14.18/CHO (dinutuximab beta) in patients with high-risk neuroblastoma (HR-NBL1/SIOPEN): a multicentre, randomised, phase 3 trial.Lancet Oncol. 2018 Dec;19(12):1617-1629. doi: 10.1016/S1470-2045(18)30578-3. Epub 2018 Nov 12.
• [6] k-RAS mutation and resistance to epidermal growth factor receptor-tyrosine kinase inhibitor treatment in patients with nonsmall cell lung cancer.J Cancer Res Ther. 2017;13(4):699-701. doi: 10.4103/jcrt.JCRT_468_17.
• [7] NBL1 and anillin (ANLN) genes over-expression in pancreatic carcinoma.Folia Histochem Cytobiol. 2009;47(2):249-55. doi: 10.2478/v10042-009-0031-1.
• [8] Ancestry and genetic associations with bronchopulmonary dysplasia in preterm infants.Am J Physiol Lung Cell Mol Physiol. 2018 Nov 1;315(5):L858-L869. doi: 10.1152/ajplung.00073.2018. Epub 2018 Aug 16.
• [9] DAN (NBL1) promotes collective neural crest migration by restraining uncontrolled invasion.J Cell Biol. 2017 Oct 2;216(10):3339-3354. doi: 10.1083/jcb.201612169. Epub 2017 Aug 15.
• [10] Synthesis and Preliminary Cytotoxicity Studies of 1-[1-(4,5-Dihydrooxazol- 2-yl)-1H-indazol-3-yl]-3-phenylurea and 3-phenylthiourea Derivatives.Med Chem. 2017;13(7):616-624. doi: 10.2174/1573406413666170306114401.
• [11] Improved gene transfer to neuroblastoma cells by a monoclonal antibody targeting RET, a receptor tyrosine kinase.Hum Gene Ther. 2000 May 1;11(7):995-1004. doi: 10.1089/10430340050015301.
• [12] The search for secreted proteins in prostate cancer by the Escherichia coli ampicillin secretion trap: expression of NBL1 is highly restricted to the prostate and is related to cancer progression.Pathobiology. 2013;80(2):60-9. doi: 10.1159/000341396. Epub 2012 Aug 29.
• [13] 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.
• [14] The RET oncogene is a critical component of transcriptional programs associated with retinoic acid-induced differentiation in neuroblastoma. Mol Cancer Ther. 2007 Apr;6(4):1300-9.
• [15] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [16] 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.
• [17] Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling. Toxicol Sci. 2014 Jun;139(2):328-37. doi: 10.1093/toxsci/kfu053. Epub 2014 Mar 27.
• [18] 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.
• [19] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [20] 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.
• [21] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [22] Cellular response to 5-fluorouracil (5-FU) in 5-FU-resistant colon cancer cell lines during treatment and recovery. Mol Cancer. 2006 May 18;5:20. doi: 10.1186/1476-4598-5-20.
• [23] Rosiglitazone sensitizes MDA-MB-231 breast cancer cells to anti-tumour effects of tumour necrosis factor-alpha, CH11 and CYC202. Endocr Relat Cancer. 2007 Jun;14(2):305-15. doi: 10.1677/ERC-06-0003.
• [24] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [25] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [26] Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res. 2007 May 15;67(10):5033-41.
• [27] 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.
• [28] 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.
• [29] Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.