Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHCFN2C)

• DOT Name: Flavin reductase (BLVRB)
• Synonyms: NADPH; FR; EC 1.5.1.30; Biliverdin reductase B; BVR-B; EC 1.3.1.24; Biliverdin-IX beta-reductase; Green heme-binding protein; GHBP; NADPH-dependent diaphorase; NADPH-flavin reductase; FLR
• Gene Name: BLVRB
• Related Disease:
  Esophageal squamous cell carcinoma
  Acute lymphocytic leukaemia
  Advanced cancer
  Childhood acute lymphoblastic leukemia
  Gastric cancer
  Gastric neoplasm
  Hepatocellular carcinoma
  Hereditary diffuse gastric adenocarcinoma
  Neurofibromatosis type 1
  Thrombocytosis disease
  Isolated congenital microcephaly
  Neoplasm
  Acute myelogenous leukaemia
  Chronic myelomonocytic leukemia
  Myelodysplastic syndrome
  Nutritional disorder
  Overnutrition
• UniProt ID: BLVRB_HUMAN
• PDB ID: 1HDO; 1HE2; 1HE3; 1HE4; 1HE5; 5OOG; 5OOH; 6OPL; 7ER6; 7ER7; 7ER8; 7ER9; 7ERA; 7ERB; 7ERC; 7ERD; 7ERE; 8ELL; 8ELM
• EC Number: 1.3.1.24; 1.5.1.30
• Pfam ID: PF13460
• Sequence:
  MAVKKIAIFGATGQTGLTTLAQAVQAGYEVTVLVRDSSRLPSEGPRPAHVVVGDVLQAAD
  VDKTVAGQDAVIVLLGTRNDLSPTTVMSEGARNIVAAMKAHGVDKVVACTSAFLLWDPTK
  VPPRLQAVTDDHIRMHKVLRESGLKYVAVMPPHIGDQPLTGAYTVTLDGRGPSRVISKHD
  LGHFMLRCLTTDEYDGHSTYPSHQYQ
• Function: Broad specificity oxidoreductase that catalyzes the NADPH-dependent reduction of a variety of flavins, such as riboflavin, FAD or FMN, biliverdins, methemoglobin and PQQ (pyrroloquinoline quinone). Contributes to heme catabolism and metabolizes linear tetrapyrroles. Can also reduce the complexed Fe(3+) iron to Fe(2+) in the presence of FMN and NADPH. In the liver, converts biliverdin to bilirubin.
• Tissue Specificity: Predominantly expressed in liver and erythrocytes. At lower levels in heart, lung, adrenal gland and cerebrum.
• KEGG Pathway:
  Riboflavin metabolism (hsa00740)
  Porphyrin metabolism (hsa00860)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Cytoprotection by HMOX1 (R-HSA-9707564)
  Heme degradation (R-HSA-189483)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal squamous cell carcinoma	DIS5N2GV	Definitive	Biomarker	[1]
Acute lymphocytic leukaemia	DISPX75S	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Altered Expression	[2]
Gastric cancer	DISXGOUK	Strong	Biomarker	[4]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[5]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[4]
Neurofibromatosis type 1	DIS53JH9	Strong	Genetic Variation	[6]
Thrombocytosis disease	DISNG0P4	Strong	Genetic Variation	[7]
Isolated congenital microcephaly	DISUXHZ6	moderate	Biomarker	[8]
Neoplasm	DISZKGEW	Disputed	Genetic Variation	[9]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[10]
Chronic myelomonocytic leukemia	DISIL8UR	Limited	Genetic Variation	[10]
Myelodysplastic syndrome	DISYHNUI	Limited	Genetic Variation	[10]
Nutritional disorder	DIS0W6QK	Limited	Biomarker	[11]
Overnutrition	DISGAJIG	Limited	Altered Expression	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Flavin reductase (BLVRB) affects the response to substance of Fluorouracil.	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Flavin reductase (BLVRB).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Flavin reductase (BLVRB).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Flavin reductase (BLVRB).	[14]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Flavin reductase (BLVRB).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Flavin reductase (BLVRB).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Flavin reductase (BLVRB).	[17]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Flavin reductase (BLVRB).	[18]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Flavin reductase (BLVRB).	[19]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Flavin reductase (BLVRB).	[20]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Flavin reductase (BLVRB).	[21]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Flavin reductase (BLVRB).	[22]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Flavin reductase (BLVRB).	[23]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Flavin reductase (BLVRB).	[24]
Selenium	DM25CGV	Approved	Selenium increases the expression of Flavin reductase (BLVRB).	[25]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Flavin reductase (BLVRB).	[26]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Flavin reductase (BLVRB).	[27]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Flavin reductase (BLVRB).	[28]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Flavin reductase (BLVRB).	[29]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Flavin reductase (BLVRB).	[30]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Flavin reductase (BLVRB).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Flavin reductase (BLVRB).	[31]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Flavin reductase (BLVRB).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Flavin reductase (BLVRB).	[33]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Flavin reductase (BLVRB).	[34]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Flavin reductase (BLVRB).	[35]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Flavin reductase (BLVRB).	[36]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Flavin reductase (BLVRB).	[37]

References

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