Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDD7G8S)

• DOT Name: Dehydrogenase/reductase SDR family member 6 (BDH2)
• Synonyms: EC 1.1.1.-; (R)-beta-hydroxybutyrate dehydrogenase; 3-hydroxybutyrate dehydrogenase type 2; EC 1.1.1.30; 4-oxo-L-proline reductase; EC 1.1.1.104; Oxidoreductase UCPA; Short chain dehydrogenase/reductase family 15C member 1
• Gene Name: BDH2
• Related Disease:
  Breast cancer
  Breast carcinoma
  Hepatocellular carcinoma
  Carcinoma of esophagus
  Esophageal cancer
  Lupus
  Neoplasm
  Neoplasm of esophagus
  Systemic lupus erythematosus
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
  Astrocytoma
  Glioblastoma multiforme
  IRIDA syndrome
  Nasopharyngeal carcinoma
• UniProt ID: DHRS6_HUMAN
• PDB ID: 2AG5
• EC Number: 1.1.1.-; 1.1.1.104; 1.1.1.30
• Pfam ID: PF13561
• Sequence:
  MGRLDGKVIILTAAAQGIGQAAALAFAREGAKVIATDINESKLQELEKYPGIQTRVLDVT
  KKKQIDQFANEVERLDVLFNVAGFVHHGTVLDCEEKDWDFSMNLNVRSMYLMIKAFLPKM
  LAQKSGNIINMSSVASSVKGVVNRCVYSTTKAAVIGLTKSVAADFIQQGIRCNCVCPGTV
  DTPSLQERIQARGNPEEARNDFLKRQKTGRFATAEEIAMLCVYLASDESAYVTGNPVIID
  GGWSL
• Function: NAD(H)-dependent dehydrogenase/reductase with a preference for cyclic substrates. Catalyzes stereoselective conversion of 4-oxo-L-proline to cis-4-hydroxy-L-proline, likely a detoxification mechanism for ketoprolines. Mediates the formation of 2,5-dihydroxybenzoate (2,5-DHBA), a siderophore that chelates free cytoplasmic iron and associates with LCN2, thereby regulating iron transport and homeostasis while protecting cells against free radical-induced oxidative stress. The iron-siderophore complex is imported into mitochondria, providing an iron source for mitochondrial metabolic processes in particular heme synthesis. May act as a 3-hydroxybutyrate dehydrogenase.
• Tissue Specificity: Detected in liver (at protein level).
• Reactome Pathway: Synthesis of Ketone Bodies (R-HSA-77111)
• BioCyc Pathway: MetaCyc:HS08987-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Definitive	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Definitive	Altered Expression	[2]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[3]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[3]
Lupus	DISOKJWA	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[3]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[4]
Epithelial ovarian cancer	DIS56MH2	moderate	Biomarker	[6]
Ovarian cancer	DISZJHAP	moderate	Biomarker	[6]
Ovarian neoplasm	DISEAFTY	moderate	Altered Expression	[6]
Astrocytoma	DISL3V18	Disputed	Altered Expression	[7]
Glioblastoma multiforme	DISK8246	Disputed	Altered Expression	[7]
IRIDA syndrome	DISPN8YW	Limited	Biomarker	[8]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[5]

3 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 Dehydrogenase/reductase SDR family member 6 (BDH2).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Dehydrogenase/reductase SDR family member 6 (BDH2).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Dehydrogenase/reductase SDR family member 6 (BDH2).	[25]

20 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 Dehydrogenase/reductase SDR family member 6 (BDH2).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Dehydrogenase/reductase SDR family member 6 (BDH2).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Dehydrogenase/reductase SDR family member 6 (BDH2).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Dehydrogenase/reductase SDR family member 6 (BDH2).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Dehydrogenase/reductase SDR family member 6 (BDH2).	[14]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Dehydrogenase/reductase SDR family member 6 (BDH2).	[15]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Dehydrogenase/reductase SDR family member 6 (BDH2).	[16]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Dehydrogenase/reductase SDR family member 6 (BDH2).	[17]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Dehydrogenase/reductase SDR family member 6 (BDH2).	[19]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Dehydrogenase/reductase SDR family member 6 (BDH2).	[20]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Dehydrogenase/reductase SDR family member 6 (BDH2).	[21]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Dehydrogenase/reductase SDR family member 6 (BDH2).	[22]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Dehydrogenase/reductase SDR family member 6 (BDH2).	[20]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Dehydrogenase/reductase SDR family member 6 (BDH2).	[23]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Dehydrogenase/reductase SDR family member 6 (BDH2).	[24]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Dehydrogenase/reductase SDR family member 6 (BDH2).	[26]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Dehydrogenase/reductase SDR family member 6 (BDH2).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Dehydrogenase/reductase SDR family member 6 (BDH2).	[28]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Dehydrogenase/reductase SDR family member 6 (BDH2).	[29]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Dehydrogenase/reductase SDR family member 6 (BDH2).	[30]

References

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