Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVVH26D)

• DOT Name: UDP-glucuronosyltransferase 2B11
• Synonyms: UDPGT 2B11; EC 2.4.1.17
• Gene Name: UGT2B11
• UniProt ID: UDB11_HUMAN
• EC Number: 2.4.1.17
• Pfam ID: PF00201
• Sequence:
  MTLKWTSVLLLIHLSCYFSSGSCGKVLVWAAEYSHWMNMKTILKELVQRGHEVTVLASSA
  SILFDPNDASTLKFEVYPTSLTKTEFENIIMQQVKRWSDIRKDSFWLYFSQEQEILWELY
  DIFRNFCKDVVSNKKVMKKLQESRFDIVFADAVFPCGELLAALLNIRFVYSLRFTPGYTI
  ERHSGGLIFPPSYIPIVMSKLSDQMTFMERVKNMIYVLYFDFWFQMSDMKKWDQFYSEVL
  GRPTTLFETMGKADIWLMRNSWSFQFPHPFLPNVDFVGGFHCKPAKPLPKEMEEFVQSSG
  ENGVVVFSLGSVISNMTAERANVIATALAKIPQKVLWRFDGNKPDALGLNTRLYKWIPQN
  DLLGHPKTRAFITHGGANGIYEAIYHGIPMVGIPLFFDQPDNIAHMKAKGAAVRLDFNTM
  SSTDLLNALKTVINDPLYKENIMKLSRIQHDQPVKPLDRAVFWIEFVMPHKGAKHLRVAA
  HDLTWFQYHSLDVIGFLLACVATVIFIITKFCLFCFWKFARKGKKGKRD
• Function: UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
• Tissue Specificity: Widely expressed.
• KEGG Pathway:
  Pentose and glucuro.te interconversions (hsa00040)
  Ascorbate and aldarate metabolism (hsa00053)
  Steroid hormone biosynthesis (hsa00140)
  Retinol metabolism (hsa00830)
  Porphyrin metabolism (hsa00860)
  Metabolism of xenobiotics by cytochrome P450 (hsa00980)
  Drug metabolism - cytochrome P450 (hsa00982)
  Drug metabolism - other enzymes (hsa00983)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
  Bile secretion (hsa04976)
  Chemical carcinogenesis - D. adducts (hsa05204)
  Chemical carcinogenesis - receptor activation (hsa05207)
• Reactome Pathway:
  Aspirin ADME (R-HSA-9749641)
  Glucuronidation (R-HSA-156588)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Biotransformations of 6 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Menthol	DMG2KW7	Approved	UDP-glucuronosyltransferase 2B11 increases the glucuronidation of Menthol.	[10]
Estriol	DMOEM2I	Approved	UDP-glucuronosyltransferase 2B11 increases the glucuronidation of Estriol.	[10]
LM-94	DMW3QGJ	Phase 1/2	UDP-glucuronosyltransferase 2B11 increases the glucuronidation of LM-94.	[10]
Mononitrophenol	DM4QO9G	Investigative	UDP-glucuronosyltransferase 2B11 increases the glucuronidation of Mononitrophenol.	[10]
BRN-1999480	DMC9Q4D	Investigative	UDP-glucuronosyltransferase 2B11 increases the glucuronidation of BRN-1999480.	[10]
Aminophenol	DMEMCQ9	Investigative	UDP-glucuronosyltransferase 2B11 increases the glucuronidation of Aminophenol.	[10]

1 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-glucuronosyltransferase 2B11.	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of UDP-glucuronosyltransferase 2B11.	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of UDP-glucuronosyltransferase 2B11.	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of UDP-glucuronosyltransferase 2B11.	[4]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of UDP-glucuronosyltransferase 2B11.	[5]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of UDP-glucuronosyltransferase 2B11.	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of UDP-glucuronosyltransferase 2B11.	[7]
Beclomethasone dipropionate	DM5NW1E	Phase 4	Beclomethasone dipropionate increases the expression of UDP-glucuronosyltransferase 2B11.	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of UDP-glucuronosyltransferase 2B11.	[9]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Research resource: STR DNA profile and gene expression comparisons of human BG-1 cells and a BG-1/MCF-7 clonal variant. Mol Endocrinol. 2014 Dec;28(12):2072-81.
• [5] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [6] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Induction of drug-metabolizing enzymes and transporters in human bronchial epithelial cells by beclomethasone dipropionate. IUBMB Life. 2004 Jun;56(6):355-9.
• [9] Modulation of gene expression and DNA adduct formation in HepG2 cells by polycyclic aromatic hydrocarbons with different carcinogenic potencies. Carcinogenesis. 2006 Mar;27(3):646-55.
• [10] cDNA cloning and expression of two new members of the human liver UDP-glucuronosyltransferase 2B subfamily. Biochem Biophys Res Commun. 1993 Jul 15;194(1):496-503.