Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4SO7J4)

• DOT Name: BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)
• Gene Name: BNIP3
• Related Disease:
  Glioma
  Alzheimer disease
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  Cardiac failure
  Chronic obstructive pulmonary disease
  Chronic renal failure
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Congestive heart failure
  Ductal breast carcinoma in situ
  End-stage renal disease
  Epithelial ovarian cancer
  Fatty liver disease
  Gastric cancer
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Hyperglycemia
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Myocardial infarction
  Neoplasm
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Ovarian cancer
  Pancreatic tumour
  Plasma cell myeloma
  Renal cell carcinoma
  Subarachnoid hemorrhage
  Metastatic malignant neoplasm
  Adenocarcinoma
  Prostate carcinoma
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  Melanoma
  Neuroblastoma
  Non-alcoholic fatty liver disease
  Obesity
  Pancreatic cancer
  Prostate cancer
  Prostate neoplasm
• UniProt ID: BNIP3_HUMAN
• PDB ID: 2J5D; 2KA1; 2KA2
• Pfam ID: PF06553
• Sequence:
  MSQNGAPGMQEESLQGSWVELHFSNNGNGGSVPASVSIYNGDMEKILLDAQHESGRSSSK
  SSHCDSPPRSQTPQDTNRASETDTHSIGEKNSSQSEEDDIERRKEVESILKKNSDWIWDW
  SSRPENIPPKEFLFKHPKRTATLSMRNTSVMKKGGIFSAEFLKVFLPSLLLSHLLAIGLG
  IYIGRRLTTSTSTF
• Function: Apoptosis-inducing protein that can overcome BCL2 suppression. May play a role in repartitioning calcium between the two major intracellular calcium stores in association with BCL2. Involved in mitochondrial quality control via its interaction with SPATA18/MIEAP: in response to mitochondrial damage, participates in mitochondrial protein catabolic process (also named MALM) leading to the degradation of damaged proteins inside mitochondria. The physical interaction of SPATA18/MIEAP, BNIP3 and BNIP3L/NIX at the mitochondrial outer membrane regulates the opening of a pore in the mitochondrial double membrane in order to mediate the translocation of lysosomal proteins from the cytoplasm to the mitochondrial matrix. Plays an important role in the calprotectin (S100A8/A9)-induced cell death pathway.
• KEGG Pathway:
  FoxO sig.ling pathway (hsa04068)
  Mitophagy - animal (hsa04137)
  Autophagy - animal (hsa04140)
  Shigellosis (hsa05131)
  Legionellosis (hsa05134)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[3]
Carcinoma	DISH9F1N	Strong	Altered Expression	[4]
Cardiac failure	DISDC067	Strong	Biomarker	[5]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Biomarker	[6]
Chronic renal failure	DISGG7K6	Strong	Biomarker	[7]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[8]
Colon cancer	DISVC52G	Strong	Altered Expression	[9]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[10]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[5]
Ductal breast carcinoma in situ	DISLCJY7	Strong	Altered Expression	[11]
End-stage renal disease	DISXA7GG	Strong	Biomarker	[7]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[12]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[13]
Gastric cancer	DISXGOUK	Strong	Biomarker	[14]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[16]
Hyperglycemia	DIS0BZB5	Strong	Biomarker	[17]
Lung cancer	DISCM4YA	Strong	Altered Expression	[18]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[18]
Lung neoplasm	DISVARNB	Strong	Biomarker	[19]
Myocardial infarction	DIS655KI	Strong	Biomarker	[20]
Neoplasm	DISZKGEW	Strong	Altered Expression	[21]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[22]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[23]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[12]
Pancreatic tumour	DIS3U0LK	Strong	Altered Expression	[24]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[25]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[8]
Subarachnoid hemorrhage	DISI7I8Y	Strong	Therapeutic	[26]
Metastatic malignant neoplasm	DIS86UK6	moderate	Altered Expression	[4]
Adenocarcinoma	DIS3IHTY	Disputed	Biomarker	[27]
Prostate carcinoma	DISMJPLE	Disputed	Posttranslational Modification	[28]
Gastric neoplasm	DISOKN4Y	Limited	Biomarker	[14]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Limited	Biomarker	[14]
Melanoma	DIS1RRCY	Limited	Biomarker	[29]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[30]
Non-alcoholic fatty liver disease	DISDG1NL	Limited	Altered Expression	[13]
Obesity	DIS47Y1K	Limited	Biomarker	[31]
Pancreatic cancer	DISJC981	Limited	Biomarker	[32]
Prostate cancer	DISF190Y	Limited	Posttranslational Modification	[28]
Prostate neoplasm	DISHDKGQ	Limited	Biomarker	[33]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) affects the response to substance of Methotrexate.	[85]
Fluorouracil	DMUM7HZ	Approved	BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) affects the response to substance of Fluorouracil.	[86]
Deoxycholic acid	DM3GYAL	Approved	BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) affects the response to substance of Deoxycholic acid.	[87]

3 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 BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[34]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[73]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[73]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[36]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[37]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[38]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[40]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[35]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[41]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[42]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[43]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[44]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[45]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[46]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[47]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[48]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[49]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[50]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[51]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[52]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[53]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[54]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[55]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[56]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[57]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[58]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[58]
Capsaicin	DMGMF6V	Approved	Capsaicin decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[59]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[60]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[60]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[61]
Dopamine	DMPGUCF	Approved	Dopamine increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[62]
Melatonin	DMKWFBT	Approved	Melatonin increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[63]
Teriflunomide	DMQ2FKJ	Approved	Teriflunomide increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[64]
Quinolones	DM5GVHU	Approved	Quinolones increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[65]
Berberine	DMC5Q8X	Phase 4	Berberine increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[66]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[67]
Chloroquine	DMSI5CB	Phase 3 Trial	Chloroquine increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[68]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[69]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[70]
AMEP	DMFELMQ	Phase 1	AMEP decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[71]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[72]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[74]
MG-132	DMKA2YS	Preclinical	MG-132 increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[56]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[75]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[76]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[51]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[77]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[78]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[79]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[71]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[80]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[81]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[82]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[43]
Bafilomycin A1	DMUNK59	Investigative	Bafilomycin A1 increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[83]
2-(carboxymethylamino)-2-oxoacetic acid	DMQ2SNL	Investigative	2-(carboxymethylamino)-2-oxoacetic acid increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3).	[84]

References

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