Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSZZP0B)

• DOT Name: UDP-glucuronosyltransferase 2B4
• Synonyms: UDPGT 2B4; UGT2B4; EC 2.4.1.17; HLUG25; Hyodeoxycholic acid-specific UDPGT; UDPGTh-1
• Gene Name: UGT2B4
• UniProt ID: UD2B4_HUMAN
• EC Number: 2.4.1.17
• Pfam ID: PF00201
• Sequence:
  MSMKWTSALLLIQLSCYFSSGSCGKVLVWPTEFSHWMNIKTILDELVQRGHEVTVLASSA
  SISFDPNSPSTLKFEVYPVSLTKTEFEDIIKQLVKRWAELPKDTFWSYFSQVQEIMWTFN
  DILRKFCKDIVSNKKLMKKLQESRFDVVLADAVFPFGELLAELLKIPFVYSLRFSPGYAI
  EKHSGGLLFPPSYVPVVMSELSDQMTFIERVKNMIYVLYFEFWFQIFDMKKWDQFYSEVL
  GRPTTLSETMAKADIWLIRNYWDFQFPHPLLPNVEFVGGLHCKPAKPLPKEMEEFVQSSG
  ENGVVVFSLGSMVSNTSEERANVIASALAKIPQKVLWRFDGNKPDTLGLNTRLYKWIPQN
  DLLGHPKTRAFITHGGANGIYEAIYHGIPMVGVPLFADQPDNIAHMKAKGAAVSLDFHTM
  SSTDLLNALKTVINDPLYKENAMKLSRIHHDQPVKPLDRAVFWIEFVMRHKGAKHLRVAA
  HDLTWFQYHSLDVTGFLLACVATVIFIITKCLFCVWKFVRTGKKGKRD
• 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 the endogenous estrogen hormones such as estradiol and estriol.
• 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 13 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Ibuprofen	DM8VCBE	Approved	UDP-glucuronosyltransferase 2B4 increases the glucuronidation of Ibuprofen.	[23]
Estriol	DMOEM2I	Approved	UDP-glucuronosyltransferase 2B4 increases the glucuronidation of Estriol.	[24]
Flurbiprofen	DMGN4BY	Approved	UDP-glucuronosyltransferase 2B4 increases the glucuronidation of Flurbiprofen.	[23]
Carvedilol	DMHTEAO	Approved	UDP-glucuronosyltransferase 2B4 increases the glucuronidation of Carvedilol.	[25]
Naproxen	DMZ5RGV	Approved	UDP-glucuronosyltransferase 2B4 increases the glucuronidation of Naproxen.	[23]
Ketoprofen	DMRKXPT	Approved	UDP-glucuronosyltransferase 2B4 increases the glucuronidation of Ketoprofen.	[23]
Amobarbital	DM0GQ8N	Approved	UDP-glucuronosyltransferase 2B4 increases the glycosylation of Amobarbital.	[26]
Ranirestat	DMD5QRS	Phase 3	UDP-glucuronosyltransferase 2B4 increases the glycosylation of Ranirestat.	[26]
Bisphenol A	DM2ZLD7	Investigative	UDP-glucuronosyltransferase 2B4 increases the glucuronidation of Bisphenol A.	[27]
Farnesol	DMV2X1B	Investigative	UDP-glucuronosyltransferase 2B4 increases the glucuronidation of Farnesol.	[28]
gingerol	DMNXYSM	Investigative	UDP-glucuronosyltransferase 2B4 increases the glucuronidation of gingerol.	[29]
ACMC-1AKLT	DMRQ70X	Investigative	UDP-glucuronosyltransferase 2B4 increases the glucuronidation of ACMC-1AKLT.	[30]
Hyodeoxycholic acid	DMSIWD0	Investigative	UDP-glucuronosyltransferase 2B4 increases the glucuronidation of Hyodeoxycholic acid.	[24]

28 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 2B4.	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of UDP-glucuronosyltransferase 2B4.	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of UDP-glucuronosyltransferase 2B4.	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of UDP-glucuronosyltransferase 2B4.	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of UDP-glucuronosyltransferase 2B4.	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of UDP-glucuronosyltransferase 2B4.	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of UDP-glucuronosyltransferase 2B4.	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of UDP-glucuronosyltransferase 2B4.	[8]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of UDP-glucuronosyltransferase 2B4.	[9]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of UDP-glucuronosyltransferase 2B4.	[10]
Nefazodone	DM4ZS8M	Approved	Nefazodone decreases the expression of UDP-glucuronosyltransferase 2B4.	[11]
Chenodiol	DMQ8JIK	Approved	Chenodiol increases the expression of UDP-glucuronosyltransferase 2B4.	[10]
Bosentan	DMIOGBU	Approved	Bosentan decreases the expression of UDP-glucuronosyltransferase 2B4.	[12]
Atazanavir	DMSYRBX	Approved	Atazanavir decreases the expression of UDP-glucuronosyltransferase 2B4.	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of UDP-glucuronosyltransferase 2B4.	[13]
Beclomethasone dipropionate	DM5NW1E	Phase 4	Beclomethasone dipropionate increases the expression of UDP-glucuronosyltransferase 2B4.	[14]
3,4-Dihydroxycinnamic Acid	DMVZL26	Phase 4	3,4-Dihydroxycinnamic Acid decreases the activity of UDP-glucuronosyltransferase 2B4.	[15]
LM-94	DMW3QGJ	Phase 1/2	LM-94 increases the activity of UDP-glucuronosyltransferase 2B4.	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of UDP-glucuronosyltransferase 2B4.	[18]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of UDP-glucuronosyltransferase 2B4.	[19]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of UDP-glucuronosyltransferase 2B4.	[20]
CATECHIN	DMY38SB	Investigative	CATECHIN decreases the activity of UDP-glucuronosyltransferase 2B4.	[15]
(E)-4-(3,5-dimethoxystyryl)phenol	DMYXI2V	Investigative	(E)-4-(3,5-dimethoxystyryl)phenol decreases the activity of UDP-glucuronosyltransferase 2B4.	[21]
Chlorogenic acid	DM2Y3P4	Investigative	Chlorogenic acid decreases the activity of UDP-glucuronosyltransferase 2B4.	[15]
P-Coumaric Acid	DMGJSVD	Investigative	P-Coumaric Acid decreases the activity of UDP-glucuronosyltransferase 2B4.	[15]
Phloretin	DMYA50U	Investigative	Phloretin decreases the activity of UDP-glucuronosyltransferase 2B4.	[15]
AMENTOFLAVONE	DMLRNV2	Investigative	AMENTOFLAVONE decreases the activity of UDP-glucuronosyltransferase 2B4.	[22]
Phlorizin	DMNARGO	Investigative	Phlorizin decreases the activity of UDP-glucuronosyltransferase 2B4.	[15]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of UDP-glucuronosyltransferase 2B4.	[17]

References

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