Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTABTFU2)

• DOT Name: UDP-glucuronosyltransferase 2B15
• Synonyms: UDPGT 2B15; UGT2B15; EC 2.4.1.17; HLUG4; UDP-glucuronosyltransferase 2B8; UDPGT 2B8; UDPGTh-3
• Gene Name: UGT2B15
• UniProt ID: UDB15_HUMAN
• PDB ID: 6IPB; 7CJX
• EC Number: 2.4.1.17
• Pfam ID: PF00201
• Sequence:
  MSLKWTSVFLLIQLSCYFSSGSCGKVLVWPTEYSHWINMKTILEELVQRGHEVTVLTSSA
  STLVNASKSSAIKLEVYPTSLTKNYLEDSLLKILDRWIYGVSKNTFWSYFSQLQELCWEY
  YDYSNKLCKDAVLNKKLMMKLQESKFDVILADALNPCGELLAELFNIPFLYSLRFSVGYT
  FEKNGGGFLFPPSYVPVVMSELSDQMIFMERIKNMIHMLYFDFWFQIYDLKKWDQFYSEV
  LGRPTTLFETMGKAEMWLIRTYWDFEFPRPFLPNVDFVGGLHCKPAKPLPKEMEEFVQSS
  GENGIVVFSLGSMISNMSEESANMIASALAQIPQKVLWRFDGKKPNTLGSNTRLYKWLPQ
  NDLLGHPKTKAFITHGGTNGIYEAIYHGIPMVGIPLFADQHDNIAHMKAKGAALSVDIRT
  MSSRDLLNALKSVINDPVYKENVMKLSRIHHDQPMKPLDRAVFWIEFVMRHKGAKHLRVA
  AHNLTWIQYHSLDVIAFLLACVATVIFIITKFCLFCFRKLAKKGKKKKRD
• Function: UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile. Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds. Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (testosterone, androsterone) and estrogens (estradiol, epiestradiol, estriol, catechol estrogens). Displays glucuronidation activity toward several classes of xenobiotic substrates, including phenolic compounds (eugenol, 4-nitrophenol, 4-hydroxybiphenyl) and phenylpropanoids (naringenin, coumarins). Catalyzes the glucuronidation of monoterpenoid alcohols such as borneol, menthol and isomenthol, a class of natural compounds used in essential oils.
• Tissue Specificity: Expressed in many tissues. Present in liver, prostate and testis.
• 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)
  Paracetamol ADME (R-HSA-9753281)
  Glucuronidation (R-HSA-156588)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 18 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	UDP-glucuronosyltransferase 2B15 increases the metabolism of Quercetin.	[22]
Dienestrol	DMBSXI0	Approved	UDP-glucuronosyltransferase 2B15 increases the metabolism of Dienestrol.	[22]
Oxazepam	DMXNZM4	Approved	UDP-glucuronosyltransferase 2B15 increases the metabolism of Oxazepam.	[26]
BAICALEIN	DM4C7E6	Phase 2	UDP-glucuronosyltransferase 2B15 increases the metabolism of BAICALEIN.	[22]
Eugenol	DM7US1H	Patented	UDP-glucuronosyltransferase 2B15 increases the metabolism of Eugenol.	[22]
EMODIN	DMAEDQG	Terminated	UDP-glucuronosyltransferase 2B15 increases the metabolism of EMODIN.	[22]
OXYQUINOLINE	DMZVS9Y	Investigative	UDP-glucuronosyltransferase 2B15 increases the metabolism of OXYQUINOLINE.	[22]
Chrysin	DM7V2LG	Investigative	UDP-glucuronosyltransferase 2B15 increases the metabolism of Chrysin.	[22]
Apigenin	DMI3491	Investigative	UDP-glucuronosyltransferase 2B15 increases the metabolism of Apigenin.	[22]
Hydroxyestradiol	DMJXQME	Investigative	UDP-glucuronosyltransferase 2B15 increases the metabolism of Hydroxyestradiol.	[22]
Mononitrophenol	DM4QO9G	Investigative	UDP-glucuronosyltransferase 2B15 increases the metabolism of Mononitrophenol.	[22]
carvacrol	DMINM2D	Investigative	UDP-glucuronosyltransferase 2B15 increases the metabolism of carvacrol.	[22]
7-hydroxycoumarin	DMTMNO7	Investigative	UDP-glucuronosyltransferase 2B15 increases the metabolism of 7-hydroxycoumarin.	[22]
Hydroxyestrone	DMBO7ZD	Investigative	UDP-glucuronosyltransferase 2B15 increases the metabolism of Hydroxyestrone.	[22]
BRN-1999480	DMC9Q4D	Investigative	UDP-glucuronosyltransferase 2B15 increases the metabolism of BRN-1999480.	[22]
SCOPOLETIN	DM645FP	Investigative	UDP-glucuronosyltransferase 2B15 increases the metabolism of SCOPOLETIN.	[22]
NSC-94258	DM6VY3P	Investigative	UDP-glucuronosyltransferase 2B15 increases the metabolism of NSC-94258.	[22]
Anthraflavic acid	DMN1YFU	Investigative	UDP-glucuronosyltransferase 2B15 increases the metabolism of Anthraflavic acid.	[22]

This DOT Affected the Biotransformations of 9 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Ibuprofen	DM8VCBE	Approved	UDP-glucuronosyltransferase 2B15 increases the glucuronidation of Ibuprofen.	[23]
Estriol	DMOEM2I	Approved	UDP-glucuronosyltransferase 2B15 increases the glucuronidation of Estriol.	[24]
Ezetimibe	DM7A8TW	Approved	UDP-glucuronosyltransferase 2B15 increases the glucuronidation of Ezetimibe.	[25]
Amobarbital	DM0GQ8N	Approved	UDP-glucuronosyltransferase 2B15 increases the glycosylation of Amobarbital.	[27]
Ranirestat	DMD5QRS	Phase 3	UDP-glucuronosyltransferase 2B15 increases the glycosylation of Ranirestat.	[27]
Phenolphthalein	DM5SICT	Withdrawn from market	UDP-glucuronosyltransferase 2B15 increases the glucuronidation of Phenolphthalein.	[28]
Tetramethylbutylphenol	DMW9CH2	Investigative	UDP-glucuronosyltransferase 2B15 increases the glucuronidation of Tetramethylbutylphenol.	[29]
ACMC-1AKLT	DMRQ70X	Investigative	UDP-glucuronosyltransferase 2B15 increases the glucuronidation of ACMC-1AKLT.	[30]
Phenolsulfonphthalein	DMCTUAD	Investigative	UDP-glucuronosyltransferase 2B15 increases the glucuronidation of Phenolsulfonphthalein.	[28]

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-glucuronosyltransferase 2B15.	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of UDP-glucuronosyltransferase 2B15.	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of UDP-glucuronosyltransferase 2B15.	[17]

31 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-glucuronosyltransferase 2B15.	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of UDP-glucuronosyltransferase 2B15.	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of UDP-glucuronosyltransferase 2B15.	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of UDP-glucuronosyltransferase 2B15.	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of UDP-glucuronosyltransferase 2B15.	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine increases the expression of UDP-glucuronosyltransferase 2B15.	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of UDP-glucuronosyltransferase 2B15.	[7]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the activity of UDP-glucuronosyltransferase 2B15.	[8]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of UDP-glucuronosyltransferase 2B15.	[9]
Osimertinib	DMRJLAT	Approved	Osimertinib decreases the activity of UDP-glucuronosyltransferase 2B15.	[10]
Flunitrazepam	DMGR5Z3	Approved	Flunitrazepam decreases the activity of UDP-glucuronosyltransferase 2B15.	[8]
Tucatinib	DMBESUA	Approved	Tucatinib decreases the activity of UDP-glucuronosyltransferase 2B15.	[11]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of UDP-glucuronosyltransferase 2B15.	[4]
3,4-Dihydroxycinnamic Acid	DMVZL26	Phase 4	3,4-Dihydroxycinnamic Acid decreases the activity of UDP-glucuronosyltransferase 2B15.	[12]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of UDP-glucuronosyltransferase 2B15.	[4]
LM-94	DMW3QGJ	Phase 1/2	LM-94 increases the activity of UDP-glucuronosyltransferase 2B15.	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of UDP-glucuronosyltransferase 2B15.	[15]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of UDP-glucuronosyltransferase 2B15.	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of UDP-glucuronosyltransferase 2B15.	[18]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the activity of UDP-glucuronosyltransferase 2B15.	[8]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide increases the expression of UDP-glucuronosyltransferase 2B15.	[4]
CATECHIN	DMY38SB	Investigative	CATECHIN decreases the activity of UDP-glucuronosyltransferase 2B15.	[12]
(E)-4-(3,5-dimethoxystyryl)phenol	DMYXI2V	Investigative	(E)-4-(3,5-dimethoxystyryl)phenol decreases the activity of UDP-glucuronosyltransferase 2B15.	[19]
Chlorogenic acid	DM2Y3P4	Investigative	Chlorogenic acid decreases the activity of UDP-glucuronosyltransferase 2B15.	[12]
Morin	DM2OGZ5	Investigative	Morin decreases the activity of UDP-glucuronosyltransferase 2B15.	[20]
Galangin	DM5TQ2O	Investigative	Galangin decreases the activity of UDP-glucuronosyltransferase 2B15.	[20]
P-Coumaric Acid	DMGJSVD	Investigative	P-Coumaric Acid decreases the activity of UDP-glucuronosyltransferase 2B15.	[12]
EPZ-004777	DMLN4V5	Investigative	EPZ-004777 increases the expression of UDP-glucuronosyltransferase 2B15.	[21]
Phloretin	DMYA50U	Investigative	Phloretin decreases the activity of UDP-glucuronosyltransferase 2B15.	[12]
propylpyrazoletriol	DMTCP8K	Investigative	propylpyrazoletriol increases the expression of UDP-glucuronosyltransferase 2B15.	[4]
Phlorizin	DMNARGO	Investigative	Phlorizin decreases the activity of UDP-glucuronosyltransferase 2B15.	[12]

References

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