Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU22H9Z)

• DOT Name: Zinc finger protein basonuclin-2 (BNC2)
• Gene Name: BNC2
• Related Disease:
  Androgen insensitivity syndrome
  Barrett esophagus
  Chronic obstructive pulmonary disease
  Endometriosis
  Epithelial ovarian cancer
  Familial multiple trichoepithelioma
  Hepatocellular carcinoma
  Hypospadias
  Isolated cleft palate
  Kidney failure
  Lower urinary tract obstruction, congenital
  Ovarian neoplasm
  Renal dysplasia
  Type-1 diabetes
  Neoplasm
  Posterior urethral valve
  Lung cancer
  Lung carcinoma
  Asthma
  Hypoglycemia
  Non-insulin dependent diabetes
  Ovarian cancer
• UniProt ID: BNC2_HUMAN
• Pfam ID: PF00096 ; PF12874
• Sequence:
  MAHLGPTPPPHSLNYKSEDRLSEQDWPAYFKVPCCGVDTSQIESEEAEVDVRERETQRDR
  EPKRARDLTLRDSCTDNSMQFGTRTTTAEPGFMGTWQNADTNLLFRMSQQAIRCTLVNCT
  CECFQPGKINLRTCDQCKHGWVAHALDKLSTQHLYHPTQVEIVQSNVVFDISSLMLYGTQ
  AVPVRLKILLDRLFSVLKQEEVLHILHGLGWTLRDYVRGYILQDAAGKVLDRWAIMSREE
  EIITLQQFLRFGETKSIVELMAIQEKEGQAVAVPSSKTDSDIRTFIESNNRTRSPSLLAH
  LENSNPSSIHHFENIPNSLAFLLPFQYINPVSAPLLGLPPNGLLLEQPGLRLREPSLSTQ
  NEYNESSESEVSPTPYKNDQTPNRNALTSITNVEPKTEPACVSPIQNSAPVSDLTKTEHP
  KSSFRIHRMRRMGSASRKGRVFCNACGKTFYDKGTLKIHYNAVHLKIKHRCTIEGCNMVF
  SSLRSRNRHSANPNPRLHMPMLRNNRDKDLIRATSGAATPVIASTKSNLALTSPGRPPMG
  FTTPPLDPVLQNPLPSQLVFSGLKTVQPVPPFYRSLLTPGEMVSPPTSLPTSPIIPTSGT
  IEQHPPPPSEPVVPAVMMATHEPSADLAPKKKPRKSSMPVKIEKEIIDTADEFDDEDDDP
  NDGGAVVNDMSHDNHCHSQEEMSPGMSVKDFSKHNRTRCISRTEIRRADSMTSEDQEPER
  DYENESESSEPKLGEESMEGDEHIHSEVSEKVLMNSERPDENHSEPSHQDVIKVKEEFTD
  PTYDMFYMSQYGLYNGGGASMAALHESFTSSLNYGSPQKFSPEGDLCSSPDPKICYVCKK
  SFKSSYSVKLHYRNVHLKEMHVCTVAGCNAAFPSRRSRDRHSANINLHRKLLTKELDDMG
  LDSSQPSLSKDLRDEFLVKIYGAQHPMGLDVREDASSPAGTEDSHLNGYGRGMAEDYMVL
  DLSTTSSLQSSSSIHSSRESDAGSDEGILLDDIDGASDSGESAHKAEAPALPGSLGAEVS
  GSLMFSSLSGSNGGIMCNICHKMYSNKGTLRVHYKTVHLREMHKCKVPGCNMMFSSVRSR
  NRHSQNPNLHKNIPFTSVD
• Function: Probable transcription factor specific for skin keratinocytes. May play a role in the differentiation of spermatozoa and oocytes. May also play an important role in early urinary-tract development.
• Tissue Specificity: Highly expressed in testis, uterus and small intestine, and weakly expressed in colon and prostate. Also expressed in skin, primary keratinocytes, immortalized keratinocytes, and HeLa and HEK293 cells. Not detected in blood, thymus, spleen or Hep-G2 cells.

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Androgen insensitivity syndrome	DISUZBBO	Definitive	Biomarker	[1]
Barrett esophagus	DIS416Y7	Strong	Altered Expression	[2]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[3]
Endometriosis	DISX1AG8	Strong	Genetic Variation	[4]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[5]
Familial multiple trichoepithelioma	DISKZAUY	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[6]
Hypospadias	DIS48CCP	Strong	Genetic Variation	[7]
Isolated cleft palate	DISV80CD	Strong	Biomarker	[8]
Kidney failure	DISOVQ9P	Strong	Biomarker	[9]
Lower urinary tract obstruction, congenital	DISPVIGA	Strong	Autosomal dominant	[10]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[11]
Renal dysplasia	DIS3DFGD	Strong	Biomarker	[9]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[12]
Neoplasm	DISZKGEW	moderate	Biomarker	[13]
Posterior urethral valve	DIS2UD2J	Supportive	Autosomal recessive	[14]
Lung cancer	DISCM4YA	Disputed	Altered Expression	[13]
Lung carcinoma	DISTR26C	Disputed	Altered Expression	[13]
Asthma	DISW9QNS	Limited	Genetic Variation	[15]
Hypoglycemia	DISRCKR7	Limited	Biomarker	[12]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[16]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Zinc finger protein basonuclin-2 (BNC2).	[18]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Zinc finger protein basonuclin-2 (BNC2).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Zinc finger protein basonuclin-2 (BNC2).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Zinc finger protein basonuclin-2 (BNC2).	[36]

21 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 Zinc finger protein basonuclin-2 (BNC2).	[20]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Zinc finger protein basonuclin-2 (BNC2).	[21]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Zinc finger protein basonuclin-2 (BNC2).	[22]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Zinc finger protein basonuclin-2 (BNC2).	[23]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Zinc finger protein basonuclin-2 (BNC2).	[24]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Zinc finger protein basonuclin-2 (BNC2).	[25]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Zinc finger protein basonuclin-2 (BNC2).	[26]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Zinc finger protein basonuclin-2 (BNC2).	[27]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Zinc finger protein basonuclin-2 (BNC2).	[28]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Zinc finger protein basonuclin-2 (BNC2).	[29]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Zinc finger protein basonuclin-2 (BNC2).	[30]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Zinc finger protein basonuclin-2 (BNC2).	[31]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Zinc finger protein basonuclin-2 (BNC2).	[32]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Zinc finger protein basonuclin-2 (BNC2).	[28]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Zinc finger protein basonuclin-2 (BNC2).	[28]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Zinc finger protein basonuclin-2 (BNC2).	[34]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Zinc finger protein basonuclin-2 (BNC2).	[35]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Zinc finger protein basonuclin-2 (BNC2).	[37]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Zinc finger protein basonuclin-2 (BNC2).	[38]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE decreases the expression of Zinc finger protein basonuclin-2 (BNC2).	[39]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone increases the expression of Zinc finger protein basonuclin-2 (BNC2).	[40]

References

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• [17] BNC2 is a putative tumor suppressor gene in high-grade serous ovarian carcinoma and impacts cell survival after oxidative stress.Cell Death Dis. 2016 Sep 22;7(9):e2374. doi: 10.1038/cddis.2016.278.
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• [40] 3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.