Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV2ZPKP)

• DOT Name: Protein aurora borealis (BORA)
• Synonyms: HsBora
• Gene Name: BORA
• Related Disease:
  Myelofibrosis
  Primary myelofibrosis
• UniProt ID: BORA_HUMAN
• Pfam ID: PF15280
• Sequence:
  MGDVKESKMQITPETPGRIPVLNPFESPSDYSNLHEQTLASPSVFKSTKLPTPGKFRWSI
  DQLAVINPVEIDPEDIHRQALYLSHSRIDKDVEDKRQKAIEEFFTKDVIVPSPWTDHEGK
  QLSQCHSSKCTNINSDSPVGKKLTIHSEKSDAACQTLLSLPVDFNLENILGDYFRADEFA
  DQSPGNLSSSSLRRKLFLDGNGSISDSLPSASPGSPHSGVQTSLEMFYSIDLSPVKCRSP
  LQTPSSGQFSSSPIQASAKKYSLGSITSPSPISSPTFSPIEFQIGETPLSEQRKFTVHSP
  DASSGTNSNGITNPCIRSPYIDGCSPIKNWSPMRLQMYSGGTQYRTSVIQIPFTLETQGE
  DEEDKENIPSTDVSSPAMDAAGIHLRQFSNEASTHGTHLVVTAMSVTQNQSSASEKELAL
  LQDVEREKDNNTVDMVDPIEIADETTWIKEPVDNGSLPMTDFVSGIAFSIENSHMCMSPL
  AESSVIPCESSNIQMDSGYNTQNCGSNIMDTVGAESYCKESDAQTCEVESKSQAFNMKQD
  HTTQRCWMKTASPFQCSSP
• Function: Required for the activation of AURKA at the onset of mitosis.
• Reactome Pathway: Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Myelofibrosis	DISIMP21	Limited	Altered Expression	[1]
Primary myelofibrosis	DIS6L0CN	Limited	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Protein aurora borealis (BORA) affects the response to substance of Topotecan.	[25]

24 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 Protein aurora borealis (BORA).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein aurora borealis (BORA).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein aurora borealis (BORA).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein aurora borealis (BORA).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein aurora borealis (BORA).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Protein aurora borealis (BORA).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein aurora borealis (BORA).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Protein aurora borealis (BORA).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Protein aurora borealis (BORA).	[7]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Protein aurora borealis (BORA).	[11]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Protein aurora borealis (BORA).	[12]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Protein aurora borealis (BORA).	[13]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Protein aurora borealis (BORA).	[14]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Protein aurora borealis (BORA).	[11]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Protein aurora borealis (BORA).	[15]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Protein aurora borealis (BORA).	[16]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Protein aurora borealis (BORA).	[17]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea decreases the expression of Protein aurora borealis (BORA).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein aurora borealis (BORA).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein aurora borealis (BORA).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein aurora borealis (BORA).	[21]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein aurora borealis (BORA).	[22]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Protein aurora borealis (BORA).	[23]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Protein aurora borealis (BORA).	[24]

2 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 Protein aurora borealis (BORA).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Protein aurora borealis (BORA).	[20]

References

• [1] Higher AURKA and PLK1 expression are associated with inferior overall survival in patients with myelofibrosis.Blood Cells Mol Dis. 2020 Mar;81:102396. doi: 10.1016/j.bcmd.2019.102396. Epub 2019 Dec 5.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Characterization of DNA reactive and non-DNA reactive anticancer drugs by gene expression profiling. Mutat Res. 2007 Jun 1;619(1-2):16-29. doi: 10.1016/j.mrfmmm.2006.12.007. Epub 2007 Feb 8.
• [12] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [13] In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells. Toxicol In Vitro. 2013 Apr;27(3):1072-81.
• [14] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [15] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [16] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [17] Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells. Mol Cancer Ther. 2012 Oct;11(10):2138-48. doi: 10.1158/1535-7163.MCT-12-0562. Epub 2012 Aug 6.
• [18] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [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] 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.
• [21] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [22] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [23] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [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.
• [25] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.