Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZS0T6O)

• DOT Name: UDP-glucose 6-dehydrogenase
• Synonyms: UDP-Glc dehydrogenase; UDP-GlcDH; UDPGDH; EC 1.1.1.22
• Gene Name: UGDH
• Related Disease: Developmental and epileptic encephalopathy, 84
• UniProt ID: UGDH_HUMAN
• PDB ID: 2Q3E; 2QG4; 3ITK; 3KHU; 3PRJ; 3PTZ; 3TDK; 3TF5; 4EDF; 4RJT; 5TJH; 5VR8; 5W4X; 6C4J; 6C4K; 6C58; 6C5A; 6C5Z
• EC Number: 1.1.1.22
• Pfam ID: PF00984 ; PF03720 ; PF03721
• Sequence:
  MFEIKKICCIGAGYVGGPTCSVIAHMCPEIRVTVVDVNESRINAWNSPTLPIYEPGLKEV
  VESCRGKNLFFSTNIDDAIKEADLVFISVNTPTKTYGMGKGRAADLKYIEACARRIVQNS
  NGYKIVTEKSTVPVRAAESIRRIFDANTKPNLNLQVLSNPEFLAEGTAIKDLKNPDRVLI
  GGDETPEGQRAVQALCAVYEHWVPREKILTTNTWSSELSKLAANAFLAQRISSINSISAL
  CEATGADVEEVATAIGMDQRIGNKFLKASVGFGGSCFQKDVLNLVYLCEALNLPEVARYW
  QQVIDMNDYQRRRFASRIIDSLFNTVTDKKIAILGFAFKKDTGDTRESSSIYISKYLMDE
  GAHLHIYDPKVPREQIVVDLSHPGVSEDDQVSRLVTISKDPYEACDGAHAVVICTEWDMF
  KELDYERIHKKMLKPAFIFDGRRVLDGLHNELQTIGFQIETIGKKVSSKRIPYAPSGEIP
  KFSLQDPPNKKPKV
• Function: Catalyzes the formation of UDP-alpha-D-glucuronate, a constituent of complex glycosaminoglycans. Required for the biosynthesis of chondroitin sulfate and heparan sulfate. Required for embryonic development via its role in the biosynthesis of glycosaminoglycans. Required for proper brain and neuronal development.
• Tissue Specificity: Detected in heart, placenta, liver, pancreas, spleen, thymus, prostate, ovary, small intestine and colon . Widely expressed .
• KEGG Pathway:
  Pentose and glucuro.te interconversions (hsa00040)
  Ascorbate and aldarate metabolism (hsa00053)
  Amino sugar and nucleotide sugar metabolism (hsa00520)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
  Biosynthesis of nucleotide sugars (hsa01250)
• Reactome Pathway: Formation of the active cofactor, UDP-glucuronate (R-HSA-173599)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Developmental and epileptic encephalopathy, 84	DISCY7U3	Strong	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	UDP-glucose 6-dehydrogenase affects the response to substance of Fluorouracil.	[24]

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 UDP-glucose 6-dehydrogenase.	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of UDP-glucose 6-dehydrogenase.	[16]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of UDP-glucose 6-dehydrogenase.	[17]

21 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 UDP-glucose 6-dehydrogenase.	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of UDP-glucose 6-dehydrogenase.	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of UDP-glucose 6-dehydrogenase.	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of UDP-glucose 6-dehydrogenase.	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of UDP-glucose 6-dehydrogenase.	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of UDP-glucose 6-dehydrogenase.	[8]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of UDP-glucose 6-dehydrogenase.	[9]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of UDP-glucose 6-dehydrogenase.	[10]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of UDP-glucose 6-dehydrogenase.	[11]
Isoflavone	DM7U58J	Phase 4	Isoflavone increases the expression of UDP-glucose 6-dehydrogenase.	[12]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of UDP-glucose 6-dehydrogenase.	[13]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of UDP-glucose 6-dehydrogenase.	[14]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin increases the expression of UDP-glucose 6-dehydrogenase.	[15]
PIPERINE	DMYEAB1	Phase 1/2	PIPERINE decreases the expression of UDP-glucose 6-dehydrogenase.	[9]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of UDP-glucose 6-dehydrogenase.	[9]
Celastrol	DMWQIJX	Preclinical	Celastrol increases the expression of UDP-glucose 6-dehydrogenase.	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of UDP-glucose 6-dehydrogenase.	[19]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of UDP-glucose 6-dehydrogenase.	[20]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of UDP-glucose 6-dehydrogenase.	[21]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of UDP-glucose 6-dehydrogenase.	[22]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of UDP-glucose 6-dehydrogenase.	[23]

References

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