Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGTQ2C9)

• DOT Name: UDP-glucuronosyltransferase 1-6
• Synonyms: UDPGT 1-6; UGT1*6; UGT1-06; UGT1.6; EC 2.4.1.17; Phenol-metabolizing UDP-glucuronosyltransferase; UDP-glucuronosyltransferase 1-F; UGT-1F; UGT1F; UDP-glucuronosyltransferase 1A6
• Gene Name: UGT1A6
• UniProt ID: UD16_HUMAN
• EC Number: 2.4.1.17
• Pfam ID: PF00201
• Sequence:
  MACLLRSFQRISAGVFFLALWGMVVGDKLLVVPQDGSHWLSMKDIVEVLSDRGHEIVVVV
  PEVNLLLKESKYYTRKIYPVPYDQEELKNRYQSFGNNHFAERSFLTAPQTEYRNNMIVIG
  LYFINCQSLLQDRDTLNFFKESKFDALFTDPALPCGVILAEYLGLPSVYLFRGFPCSLEH
  TFSRSPDPVSYIPRCYTKFSDHMTFSQRVANFLVNLLEPYLFYCLFSKYEELASAVLKRD
  VDIITLYQKVSVWLLRYDFVLEYPRPVMPNMVFIGGINCKKRKDLSQEFEAYINASGEHG
  IVVFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQNDLL
  GHPMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMTSE
  DLENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHDL
  TWYQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH
• Function: UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 3 lacks transferase activity but acts as a negative regulator of isoform 1.
• Tissue Specificity: Expressed in skin. Isoforms 1 and 3 are expressed in kidney and liver. Isoform 1 but not isoform 2 is expressed in colon, esophagus and small intestine.
• 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 Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	UDP-glucuronosyltransferase 1-6 increases the Cardiotoxicity ADR of Doxorubicin.	[33]
Cisplatin	DMRHGI9	Approved	UDP-glucuronosyltransferase 1-6 affects the response to substance of Cisplatin.	[34]
Daunorubicin	DMQUSBT	Approved	UDP-glucuronosyltransferase 1-6 increases the Cardiotoxicity ADR of Daunorubicin.	[33]

This DOT Affected the Biotransformations of 12 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Irinotecan	DMP6SC2	Approved	UDP-glucuronosyltransferase 1-6 increases the glucuronidation of Irinotecan.	[35]
Morphine	DMRMS0L	Approved	UDP-glucuronosyltransferase 1-6 increases the glucuronidation of Morphine.	[36]
Flurbiprofen	DMGN4BY	Approved	UDP-glucuronosyltransferase 1-6 increases the glucuronidation of Flurbiprofen.	[37]
Naproxen	DMZ5RGV	Approved	UDP-glucuronosyltransferase 1-6 increases the glucuronidation of Naproxen.	[37]
Ketoprofen	DMRKXPT	Approved	UDP-glucuronosyltransferase 1-6 increases the glucuronidation of Ketoprofen.	[37]
Chrysin	DM7V2LG	Investigative	UDP-glucuronosyltransferase 1-6 affects the glucuronidation of Chrysin.	[39]
Farnesol	DMV2X1B	Investigative	UDP-glucuronosyltransferase 1-6 increases the glucuronidation of Farnesol.	[40]
Serotonin	DMOFCRY	Investigative	UDP-glucuronosyltransferase 1-6 increases the glucuronidation of Serotonin.	[41]
Mononitrophenol	DM4QO9G	Investigative	UDP-glucuronosyltransferase 1-6 increases the glucuronidation of Mononitrophenol.	[42]
ACMC-1AKLT	DMRQ70X	Investigative	UDP-glucuronosyltransferase 1-6 increases the glucuronidation of ACMC-1AKLT.	[43]
SCOPOLETIN	DM645FP	Investigative	UDP-glucuronosyltransferase 1-6 increases the glucuronidation of SCOPOLETIN.	[44]
N-acetylserotonin	DMJ4SBM	Investigative	UDP-glucuronosyltransferase 1-6 increases the glucuronidation of N-acetylserotonin.	[45]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Puerarin	DMJIMXH	Phase 2	UDP-glucuronosyltransferase 1-6 increases the metabolism of Puerarin.	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of UDP-glucuronosyltransferase 1-6.	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of UDP-glucuronosyltransferase 1-6.	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of UDP-glucuronosyltransferase 1-6.	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of UDP-glucuronosyltransferase 1-6.	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of UDP-glucuronosyltransferase 1-6.	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of UDP-glucuronosyltransferase 1-6.	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of UDP-glucuronosyltransferase 1-6.	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of UDP-glucuronosyltransferase 1-6.	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of UDP-glucuronosyltransferase 1-6.	[9]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of UDP-glucuronosyltransferase 1-6.	[10]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of UDP-glucuronosyltransferase 1-6.	[5]
Chenodiol	DMQ8JIK	Approved	Chenodiol decreases the expression of UDP-glucuronosyltransferase 1-6.	[11]
Bosentan	DMIOGBU	Approved	Bosentan decreases the expression of UDP-glucuronosyltransferase 1-6.	[12]
Omeprazole	DM471KJ	Approved	Omeprazole increases the expression of UDP-glucuronosyltransferase 1-6.	[13]
Osimertinib	DMRJLAT	Approved	Osimertinib decreases the activity of UDP-glucuronosyltransferase 1-6.	[14]
Tucatinib	DMBESUA	Approved	Tucatinib decreases the activity of UDP-glucuronosyltransferase 1-6.	[15]
3,4-Dihydroxycinnamic Acid	DMVZL26	Phase 4	3,4-Dihydroxycinnamic Acid decreases the activity of UDP-glucuronosyltransferase 1-6.	[16]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of UDP-glucuronosyltransferase 1-6.	[17]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of UDP-glucuronosyltransferase 1-6.	[19]
Disulfiram	DMCL2OK	Phase 2 Trial	Disulfiram increases the expression of UDP-glucuronosyltransferase 1-6.	[19]
LM-94	DMW3QGJ	Phase 1/2	LM-94 increases the activity of UDP-glucuronosyltransferase 1-6.	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of UDP-glucuronosyltransferase 1-6.	[21]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of UDP-glucuronosyltransferase 1-6.	[22]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of UDP-glucuronosyltransferase 1-6.	[19]
PIRINIXIC ACID	DM82Y75	Preclinical	PIRINIXIC ACID increases the expression of UDP-glucuronosyltransferase 1-6.	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of UDP-glucuronosyltransferase 1-6.	[24]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of UDP-glucuronosyltransferase 1-6.	[25]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of UDP-glucuronosyltransferase 1-6.	[26]
CATECHIN	DMY38SB	Investigative	CATECHIN decreases the activity of UDP-glucuronosyltransferase 1-6.	[16]
(E)-4-(3,5-dimethoxystyryl)phenol	DMYXI2V	Investigative	(E)-4-(3,5-dimethoxystyryl)phenol decreases the activity of UDP-glucuronosyltransferase 1-6.	[27]
2-tert-butylbenzene-1,4-diol	DMNXI1E	Investigative	2-tert-butylbenzene-1,4-diol increases the expression of UDP-glucuronosyltransferase 1-6.	[28]
Myricetin	DMTV4L0	Investigative	Myricetin decreases the activity of UDP-glucuronosyltransferase 1-6.	[29]
Chlorogenic acid	DM2Y3P4	Investigative	Chlorogenic acid decreases the activity of UDP-glucuronosyltransferase 1-6.	[16]
Morin	DM2OGZ5	Investigative	Morin decreases the activity of UDP-glucuronosyltransferase 1-6.	[29]
Piceatannol	DMYOP45	Investigative	Piceatannol decreases the activity of UDP-glucuronosyltransferase 1-6.	[30]
Galangin	DM5TQ2O	Investigative	Galangin decreases the activity of UDP-glucuronosyltransferase 1-6.	[29]
Phloretin	DMYA50U	Investigative	Phloretin decreases the activity of UDP-glucuronosyltransferase 1-6.	[16]
AMENTOFLAVONE	DMLRNV2	Investigative	AMENTOFLAVONE decreases the activity of UDP-glucuronosyltransferase 1-6.	[31]
pregnenolone-16alpha-carbonitrile	DM0LW7G	Investigative	pregnenolone-16alpha-carbonitrile increases the expression of UDP-glucuronosyltransferase 1-6.	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Camptothecin	DM6CHNJ	Phase 3	Camptothecin decreases the methylation of UDP-glucuronosyltransferase 1-6.	[18]

References

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