UDP-glucuronosyltransferase 1-1
Details
- Name
- UDP-glucuronosyltransferase 1-1
- Synonyms
- 2.4.1.17
- Bilirubin-specific UDPGT isozyme 1
- GNT1
- hUG-BR1
- UDP-glucuronosyltransferase 1-A
- UDP-glucuronosyltransferase 1A1
- UDPGT 1-1
- UGT-1A
- UGT1
- UGT1A
- Gene Name
- UGT1A1
- Organism
- Humans
- Amino acid sequence
>lcl|BSEQ0006823|UDP-glucuronosyltransferase 1-1 MAVESQGGRPLVLGLLLCVLGPVVSHAGKILLIPVDGSHWLSMLGAIQQLQQRGHEIVVL APDASLYIRDGAFYTLKTYPVPFQREDVKESFVSLGHNVFENDSFLQRVIKTYKKIKKDS AMLLSGCSHLLHNKELMASLAESSFDVMLTDPFLPCSPIVAQYLSLPTVFFLHALPCSLE FEATQCPNPFSYVPRPLSSHSDHMTFLQRVKNMLIAFSQNFLCDVVYSPYATLASEFLQR EVTVQDLLSSASVWLFRSDFVKDYPRPIMPNMVFVGGINCLHQNPLSQEFEAYINASGEH GIVVFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQNDL LGHPMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMTS EDLENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHD LTWYQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH
- Number of residues
- 533
- Molecular Weight
- 59590.91
- Theoretical pI
- 8.09
- GO Classification
- Functionsenzyme binding / enzyme inhibitor activity / glucuronosyltransferase activity / protein heterodimerization activity / protein homodimerization activity / retinoic acid binding / steroid bindingProcessesacute-phase response / bilirubin conjugation / biphenyl catabolic process / cellular glucuronidation / cellular response to ethanol / cellular response to glucocorticoid stimulus / cellular response to hormone stimulus / digestion / drug metabolic process / estrogen metabolic process / flavone metabolic process / flavonoid biosynthetic process / flavonoid glucuronidation / heme catabolic process / heterocycle metabolic process / liver development / negative regulation of catalytic activity / negative regulation of cellular glucuronidation / negative regulation of fatty acid metabolic process / negative regulation of glucuronosyltransferase activity / negative regulation of steroid metabolic process / organ regeneration / porphyrin-containing compound metabolic process / response to drug / response to lipopolysaccharide / response to nutrient / response to starvation / retinoic acid metabolic process / small molecule metabolic process / steroid metabolic process / xenobiotic glucuronidation / xenobiotic metabolic processComponentscytochrome complex / endoplasmic reticulum / endoplasmic reticulum chaperone complex / endoplasmic reticulum membrane / integral component of plasma membrane
- General Function
- Steroid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naphthol, paranitrophenol, scopoletin, and umbelliferone. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1.
- Pfam Domain Function
- UDPGT (PF00201)
- Transmembrane Regions
- 491-507
- Cellular Location
- Microsome
- Gene sequence
>lcl|BSEQ0021360|UDP-glucuronosyltransferase 1-1 (UGT1A1) ATGGCTGTGGAGTCCCAGGGCGGACGCCCACTTGTCCTGGGCCTGCTGCTGTGTGTGCTG GGCCCAGTGGTGTCCCATGCTGGGAAGATACTGTTGATCCCAGTGGATGGCAGCCACTGG CTGAGCATGCTTGGGGCCATCCAGCAGCTGCAGCAGAGGGGACATGAAATAGTTGTCCTA GCACCTGACGCCTCGTTGTACATCAGAGACGGAGCATTTTACACCTTGAAGACGTACCCT GTGCCATTCCAAAGGGAGGATGTGAAAGAGTCTTTTGTTAGTCTCGGGCATAATGTTTTT GAGAATGATTCTTTCCTGCAGCGTGTGATCAAAACATACAAGAAAATAAAAAAGGACTCT GCTATGCTTTTGTCTGGCTGTTCCCACTTACTGCACAACAAGGAGCTCATGGCCTCCCTG GCAGAAAGCAGCTTTGATGTCATGCTGACGGACCCTTTCCTTCCTTGCAGCCCCATCGTG GCCCAGTACCTGTCTCTGCCCACTGTATTCTTCTTGCATGCACTGCCATGCAGCCTGGAA TTTGAGGCTACCCAGTGCCCCAACCCATTCTCCTACGTGCCCAGGCCTCTCTCCTCTCAT TCAGATCACATGACCTTCCTGCAGCGGGTGAAGAACATGCTCATTGCCTTTTCACAGAAC TTTCTGTGCGACGTGGTTTATTCCCCGTATGCAACCCTTGCCTCAGAATTCCTTCAGAGA GAGGTGACTGTCCAGGACCTATTGAGCTCTGCATCTGTCTGGCTGTTTAGAAGTGACTTT GTGAAGGATTACCCTAGGCCCATCATGCCCAATATGGTTTTTGTTGGTGGAATCAACTGC CTTCACCAAAATCCACTATCCCAGGAATTTGAAGCCTACATTAATGCTTCTGGAGAACAT GGAATTGTGGTTTTCTCTTTGGGATCAATGGTCTCAGAAATTCCAGAGAAGAAAGCTATG GCAATTGCTGATGCTTTGGGCAAAATCCCTCAGACAGTCCTGTGGCGGTACACTGGAACC CGACCATCGAATCTTGCGAACAACACGATACTTGTTAAGTGGCTACCCCAAAACGATCTG CTTGGTCACCCGATGACCCGTGCCTTTATCACCCATGCTGGTTCCCATGGTGTTTATGAA AGCATATGCAATGGCGTTCCCATGGTGATGATGCCCTTGTTTGGTGATCAGATGGACAAT GCAAAGCGCATGGAGACTAAGGGAGCTGGAGTGACCCTGAATGTTCTGGAAATGACTTCT GAAGATTTAGAAAATGCTCTAAAAGCAGTCATCAATGACAAAAGTTACAAGGAGAACATC ATGCGCCTCTCCAGCCTTCACAAGGACCGCCCGGTGGAGCCGCTGGACCTGGCCGTGTTC TGGGTGGAGTTTGTGATGAGGCACAAGGGCGCGCCACACCTGCGCCCCGCAGCCCACGAC CTCACCTGGTACCAGTACCATTCCTTGGACGTGATTGGTTTCCTCTTGGCCGTCGTGCTG ACAGTGGCCTTCATCACCTTTAAATGTTGTGCTTATGGCTACCGGAAATGCTTGGGGAAA AAAGGGCGAGTTAAGAAAGCCCACAAATCCAAGACCCATTGA
- Chromosome Location
- 2
- Locus
- 2q37
- External Identifiers
Resource Link UniProtKB ID P22309 UniProtKB Entry Name UD11_HUMAN GenBank Protein ID 184473 GenBank Gene ID M57899 HGNC ID HGNC:12530 - General References
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- Tang L, Singh R, Liu Z, Hu M: Structure and concentration changes affect characterization of UGT isoform-specific metabolism of isoflavones. Mol Pharm. 2009 Sep-Oct;6(5):1466-82. doi: 10.1021/mp8002557. [Article]
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- Johnson AD, Kavousi M, Smith AV, Chen MH, Dehghan A, Aspelund T, Lin JP, van Duijn CM, Harris TB, Cupples LA, Uitterlinden AG, Launer L, Hofman A, Rivadeneira F, Stricker B, Yang Q, O'Donnell CJ, Gudnason V, Witteman JC: Genome-wide association meta-analysis for total serum bilirubin levels. Hum Mol Genet. 2009 Jul 15;18(14):2700-10. doi: 10.1093/hmg/ddp202. Epub 2009 May 4. [Article]
- Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. [Article]
- Bellemare J, Rouleau M, Girard H, Harvey M, Guillemette C: Alternatively spliced products of the UGT1A gene interact with the enzymatically active proteins to inhibit glucuronosyltransferase activity in vitro. Drug Metab Dispos. 2010 Oct;38(10):1785-9. doi: 10.1124/dmd.110.034835. Epub 2010 Jul 7. [Article]
- Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
- Bosma PJ, Chowdhury JR, Huang TJ, Lahiri P, Elferink RP, Van Es HH, Lederstein M, Whitington PF, Jansen PL, Chowdhury NR: Mechanisms of inherited deficiencies of multiple UDP-glucuronosyltransferase isoforms in two patients with Crigler-Najjar syndrome, type I. FASEB J. 1992 Jul;6(10):2859-63. [Article]
- Aono S, Yamada Y, Keino H, Hanada N, Nakagawa T, Sasaoka Y, Yazawa T, Sato H, Koiwai O: Identification of defect in the genes for bilirubin UDP-glucuronosyl-transferase in a patient with Crigler-Najjar syndrome type II. Biochem Biophys Res Commun. 1993 Dec 30;197(3):1239-44. [Article]
- Moghrabi N, Clarke DJ, Boxer M, Burchell B: Identification of an A-to-G missense mutation in exon 2 of the UGT1 gene complex that causes Crigler-Najjar syndrome type 2. Genomics. 1993 Oct;18(1):171-3. [Article]
- Ritter JK, Yeatman MT, Kaiser C, Gridelli B, Owens IS: A phenylalanine codon deletion at the UGT1 gene complex locus of a Crigler-Najjar type I patient generates a pH-sensitive bilirubin UDP-glucuronosyltransferase. J Biol Chem. 1993 Nov 5;268(31):23573-9. [Article]
- Labrune P, Myara A, Hadchouel M, Ronchi F, Bernard O, Trivin F, Chowdhury NR, Chowdhury JR, Munnich A, Odievre M: Genetic heterogeneity of Crigler-Najjar syndrome type I: a study of 14 cases. Hum Genet. 1994 Dec;94(6):693-7. [Article]
- Erps LT, Ritter JK, Hersh JH, Blossom D, Martin NC, Owens IS: Identification of two single base substitutions in the UGT1 gene locus which abolish bilirubin uridine diphosphate glucuronosyltransferase activity in vitro. J Clin Invest. 1994 Feb;93(2):564-70. [Article]
- Seppen J, Bosma PJ, Goldhoorn BG, Bakker CT, Chowdhury JR, Chowdhury NR, Jansen PL, Oude Elferink RP: Discrimination between Crigler-Najjar type I and II by expression of mutant bilirubin uridine diphosphate-glucuronosyltransferase. J Clin Invest. 1994 Dec;94(6):2385-91. [Article]
- Aono S, Adachi Y, Uyama E, Yamada Y, Keino H, Nanno T, Koiwai O, Sato H: Analysis of genes for bilirubin UDP-glucuronosyltransferase in Gilbert's syndrome. Lancet. 1995 Apr 15;345(8955):958-9. [Article]
- Seppen J, Steenken E, Lindhout D, Bosma PJ, Elferink RP: A mutation which disrupts the hydrophobic core of the signal peptide of bilirubin UDP-glucuronosyltransferase, an endoplasmic reticulum membrane protein, causes Crigler-Najjar type II. FEBS Lett. 1996 Jul 29;390(3):294-8. [Article]
- Ciotti M, Chen F, Rubaltelli FF, Owens IS: Coding defect and a TATA box mutation at the bilirubin UDP-glucuronosyltransferase gene cause Crigler-Najjar type I disease. Biochim Biophys Acta. 1998 Jul 1;1407(1):40-50. [Article]
- Yamamoto K, Soeda Y, Kamisako T, Hosaka H, Fukano M, Sato H, Fujiyama Y, Adachi Y, Satoh Y, Bamba T: Analysis of bilirubin uridine 5'-diphosphate (UDP)-glucuronosyltransferase gene mutations in seven patients with Crigler-Najjar syndrome type II. J Hum Genet. 1998;43(2):111-4. [Article]
- Maruo Y, Sato H, Yamano T, Doida Y, Shimada M: Gilbert syndrome caused by a homozygous missense mutation (Tyr486Asp) of bilirubin UDP-glucuronosyltransferase gene. J Pediatr. 1998 Jun;132(6):1045-7. [Article]
- Kadakol A, Ghosh SS, Sappal BS, Sharma G, Chowdhury JR, Chowdhury NR: Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype. Hum Mutat. 2000 Oct;16(4):297-306. [Article]
- Maruo Y, Nishizawa K, Sato H, Sawa H, Shimada M: Prolonged unconjugated hyperbilirubinemia associated with breast milk and mutations of the bilirubin uridine diphosphate- glucuronosyltransferase gene. Pediatrics. 2000 Nov;106(5):E59. [Article]
- Kadakol A, Sappal BS, Ghosh SS, Lowenheim M, Chowdhury A, Chowdhury S, Santra A, Arias IM, Chowdhury JR, Chowdhury NR: Interaction of coding region mutations and the Gilbert-type promoter abnormality of the UGT1A1 gene causes moderate degrees of unconjugated hyperbilirubinaemia and may lead to neonatal kernicterus. J Med Genet. 2001 Apr;38(4):244-9. [Article]
- Labrune P, Myara A, Chalas J, Le Bihan B, Capel L, Francoual J: Association of a homozygous (TA)8 promoter polymorphism and a N400D mutation of UGT1A1 in a child with Crigler-Najjar type II syndrome. Hum Mutat. 2002 Nov;20(5):399-401. [Article]
- Sutomo R, Laosombat V, Sadewa AH, Yokoyama N, Nakamura H, Matsuo M, Nishio H: Novel missense mutation of the UGT1A1 gene in Thai siblings with Gilbert's syndrome. Pediatr Int. 2002 Aug;44(4):427-32. [Article]
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Drug Relations
- Drug Relations
DrugBank ID Name Drug group Pharmacological action? Actions Details DB00688 Mycophenolate mofetil approved, investigational unknown substrate Details DB01024 Mycophenolic acid approved, investigational unknown substrate Details DB01048 Abacavir approved, investigational unknown substrate Details DB00173 Adenine approved, nutraceutical unknown inhibitor Details DB00197 Troglitazone approved, investigational, withdrawn unknown substrate Details DB00762 Irinotecan approved, investigational unknown substrate Details DB00783 Estradiol approved, investigational, vet_approved unknown substrate Details DB00818 Propofol approved, investigational, vet_approved unknown substrateinhibitor Details DB00973 Ezetimibe approved unknown substrate Details DB01045 Rifampicin approved unknown inducer Details DB00678 Losartan approved unknown substrate Details DB00712 Flurbiprofen approved, investigational unknown substrateinhibitor Details DB00328 Indomethacin approved, investigational unknown substrateinhibitor Details DB00870 Suprofen approved, withdrawn unknown substrate Details DB06741 Gavestinel investigational unknown substrate Details DB04868 Nilotinib approved, investigational unknown inhibitor Details DB06210 Eltrombopag approved unknown substrateinhibitor Details DB00295 Morphine approved, investigational no substrate Details DB05039 Indacaterol approved unknown substrate Details DB06510 Muraglitazar investigational unknown substrate Details DB00704 Naltrexone approved, investigational, vet_approved unknown substrate Details DB06817 Raltegravir approved unknown substrate Details DB04953 Ezogabine approved, investigational unknown substrate Details DB01420 Testosterone propionate approved, investigational, vet_approved, withdrawn unknown inducer Details DB06589 Pazopanib approved unknown inhibitor Details DB06626 Axitinib approved, investigational no substrate Details DB08896 Regorafenib approved unknown inhibitor Details DB00316 Acetaminophen approved unknown substrate Details DB01076 Atorvastatin approved no substrate Details DB00227 Lovastatin approved, investigational no substrate Details DB00641 Simvastatin approved unknown substrate Details DB01544 Flunitrazepam approved, illicit unknown inhibitor Details DB00530 Erlotinib approved, investigational unknown inhibitor Details DB00773 Etoposide approved unknown substrate Details DB01095 Fluvastatin approved unknown substrate Details DB00398 Sorafenib approved, investigational unknown inhibitor Details DB08930 Dolutegravir approved no substrate Details DB09101 Elvitegravir approved no substrate Details DB09183 Dasabuvir approved unknown inhibitor Details DB05015 Belinostat approved, investigational unknown substrate Details DB11943 Delafloxacin approved, investigational no substrate Details DB13874 Enasidenib approved, investigational unknown substrateinhibitor Details DB13878 Pibrentasvir approved, investigational unknown inhibitor Details DB13879 Glecaprevir approved, investigational unknown inhibitor Details DB12070 Letermovir approved, investigational no substrate Details DB12332 Rucaparib approved, investigational no inhibitor Details DB11827 Ertugliflozin approved, investigational no inhibitor Details DB13952 Estradiol acetate approved, investigational, vet_approved unknown substrate Details DB13953 Estradiol benzoate approved, investigational, vet_approved unknown substrate Details DB13954 Estradiol cypionate approved, investigational, vet_approved unknown substrate Details DB13955 Estradiol dienanthate approved, investigational, vet_approved unknown substrate Details DB13956 Estradiol valerate approved, investigational, vet_approved unknown substrate Details DB11799 Bictegravir approved, investigational unknown substrate Details DB12010 Fostamatinib approved, investigational unknown inhibitor Details DB01026 Ketoconazole approved, investigational unknown inhibitor Details DB00224 Indinavir approved unknown inhibitor Details DB00564 Carbamazepine approved, investigational no inducer Details DB00252 Phenytoin approved, vet_approved no substrateinducer Details DB01174 Phenobarbital approved, investigational no inducer Details DB00932 Tipranavir approved, investigational no inducer Details DB00220 Nelfinavir approved no inducer Details DB00625 Efavirenz approved, investigational no inducer Details DB00906 Tiagabine approved, investigational no substrate Details DB00313 Valproic acid approved, investigational no substrateinhibitor Details DB00909 Zonisamide approved, investigational no substrate Details DB01136 Carvedilol approved, investigational no substrate Details DB03496 Alvocidib experimental, investigational no substrate Details DB00695 Furosemide approved, vet_approved no substrate Details DB01241 Gemfibrozil approved no substrateinhibitor Details DB01067 Glipizide approved, investigational no substrate Details DB00451 Levothyroxine approved no substrate Details DB00916 Metronidazole approved no substrate Details DB01183 Naloxone approved, vet_approved no substrate Details DB00481 Raloxifene approved, investigational no substrate Details DB00193 Tramadol approved, investigational no substrate Details DB00495 Zidovudine approved no substrateinducer Details DB09298 Silibinin experimental, investigational no inhibitor Details DB09276 Sodium aurothiomalate approved, investigational no inhibitor Details DB00977 Ethinylestradiol approved no substrateinducer Details DB00439 Cerivastatin approved, withdrawn no substrate Details DB00947 Fulvestrant approved, investigational no substrate Details DB01009 Ketoprofen approved, vet_approved no substrate Details DB11967 Binimetinib approved, investigational no substrate Details DB01072 Atazanavir approved, investigational no inhibitor Details DB12020 Tecovirimat approved, investigational unknown substrate Details DB02703 Fusidic acid approved, investigational unknown substrate Details DB09288 Propacetamol experimental no substrate Details DB01609 Deferasirox approved, investigational unknown substrateinhibitor Details DB14575 Eslicarbazepine approved unknown substrate Details DB09213 Dexibuprofen approved, investigational unknown substrate Details DB09119 Eslicarbazepine acetate approved unknown substrate Details DB11963 Dacomitinib approved, investigational no inhibitor Details DB01032 Probenecid approved, investigational no inhibitor Details DB00350 Minoxidil approved, investigational no substrate Details DB00279 Liothyronine approved, vet_approved no substrate Details DB00304 Desogestrel approved no inducer Details DB00598 Labetalol approved unknown substrate Details DB12978 Pexidartinib approved, investigational unknown inhibitor Details DB09297 Paritaprevir approved, investigational unknown inhibitor Details DB09079 Nintedanib approved unknown substrate Details DB00455 Loratadine approved, investigational unknown Details DB06077 Lumateperone approved, investigational no substrate Details DB15328 Ubrogepant approved, investigational unknown inhibitor Details DB00957 Norgestimate approved, investigational unknown substrate Details DB11689 Selumetinib approved, investigational no substrate Details DB12893 Sacituzumab govitecan approved, investigational no substrate Details DB15456 Vericiguat approved, investigational unknown substrate Details DB09296 Ombitasvir approved, investigational unknown inhibitor Details DB11751 Cabotegravir approved, investigational unknown substrate Details DB04854 Febuxostat approved no substrate Details DB12016 Ponesimod approved, investigational unknown substrate Details DB08804 Nandrolone decanoate approved, illicit unknown substrate Details DB16703 Belumosudil approved, investigational no inhibitor Details DB12597 Asciminib approved, investigational no inhibitor Details DB12713 Sotagliflozin approved, investigational no substrate Details DB16236 Mitapivat approved, investigational no inducer Details DB09074 Olaparib approved unknown inhibitor Details DB08912 Dabrafenib approved, investigational no inhibitor Details DB15673 Lenacapavir approved, investigational no substrate Details DB00470 Dronabinol approved, illicit no substrate Details DB12243 Edaravone approved, investigational no substrate Details DB12236 Bexagliflozin approved, investigational unknown substrate Details DB00349 Clobazam approved, illicit no upregulator Details DB12255 Vadadustat approved, investigational unknown substrateinducer Details DB12874 Quizartinib approved, investigational no inhibitor Details DB06700 Desvenlafaxine approved, investigational no substrate Details DB11763 Momelotinib approved, investigational unknown inhibitorinducer Details DB11718 Encorafenib approved, investigational no inhibitor Details DB16826 Repotrectinib approved, investigational no inhibitor Details DB16200 Iptacopan approved, investigational no substrate Details DB00555 Lamotrigine approved, investigational unknown substrate Details DB00503 Ritonavir approved, investigational no inducer Details DB14635 Curcumin sulfate experimental unknown inhibitor Details DB00794 Primidone approved, vet_approved unknown inducer Details DB00783 Estradiol approved, investigational, vet_approved unknown substrateinducer Details DB00714 Apomorphine approved, investigational unknown substrate Details DB11796 Fostemsavir approved, investigational unknown substrate Details DB00871 Terbutaline approved unknown substrate Details DB00960 Pindolol approved, investigational unknown substrate Details DB12471 Ibrexafungerp approved, investigational unknown substrate Details