Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMEL9UT)

• Drug Name: taurochenodeoxycholic acid Drug Info
• Synonyms: taurochenodeoxycholate

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 387316
  ChEBI ID: CHEBI:16525
  CAS Number: CAS 516-35-8
  TTD Drug ID: DMEL9UT
  INTEDE Drug ID: DR1535

Molecule-Related Drug Atlas

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[5]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[6]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[7]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[8]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[9]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[10]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[11]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[12]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[6]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[13]
Eplerenone	DMF0NQR	Heart failure	BD10-BD13	Approved	[14]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[15]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[16]
Voriconazole	DMAOL2S	Aspergillosis	1F20	Approved	[17]
Proguanil	DMBL79I	Malaria	1F40-1F45	Approved	[18]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[18]
Loratadine	DMF3AN7	Allergy	4A80-4A85	Approved	[19]
Nelfinavir mesylate	DMFX6G8	N. A.	N. A.	Approved	[20]
Capsaicin	DMGMF6V	Back pain	ME84.Z	Approved	[21]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[22]

Drug(s) Affected By Solute carrier organic anion transporter family member 1B1 (SLCO1B1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[23]
Lovastatin	DM9OZWQ	Arteriosclerosis	BD40	Approved	[24]
Bosentan	DMIOGBU	Pulmonary arterial hypertension	BB01.0	Approved	[25]
Repaglinide	DM5SXUV	Diabetic complication	5A2Y	Approved	[26]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[27]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[28]
Cholic Acid	DM7OKQV	Cholelithiasis	DC11	Approved	[29]
Ursodeoxycholic acid	DMCUT21	Cholelithiasis	DC11	Approved	[29]
Hydroxyurea	DMOQVU9	Chronic myelogenous leukaemia	2A20.0	Approved	[30]
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[31]

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Biotransformations	[3]
Solute carrier organic anion transporter family member 1B1 (SLCO1B1)	OTNEN8QK	SO1B1_HUMAN	Regulation of Drug Effects	[4]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4747).
• [2] 6alpha-hydroxylation of taurochenodeoxycholic acid and lithocholic acid by CYP3A4 in human liver microsomes. Biochim Biophys Acta. 1999 Apr 19;1438(1):47-54.
• [3] Novel insights into bile acid detoxification via CYP, UGT and SULT enzymes. Toxicol In Vitro. 2023 Mar;87:105533. doi: 10.1016/j.tiv.2022.105533. Epub 2022 Dec 5.
• [4] Human OATP1B1 (SLCO1B1) transports sulfated bile acids and bile salts with particular efficiency. Toxicol In Vitro. 2018 Oct;52:189-194. doi: 10.1016/j.tiv.2018.06.018. Epub 2018 Jun 19.
• [5] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [6] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [7] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [8] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [9] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [10] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [11] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [12] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [13] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [14] The relative role of CYP3A4 and CYP3A5 in eplerenone metabolism. Toxicol Lett. 2019 Oct 15;315:9-13.
• [15] Characterization of the structural determinants required for potent mechanism-based inhibition of human cytochrome P450 1A1 by cannabidiol. Chem Biol Interact. 2014 May 25;215:62-8.
• [16] Retinoids activate the RXR/SXR-mediated pathway and induce the endogenous CYP3A4 activity in Huh7 human hepatoma cells. Toxicol Sci. 2006 Jul;92(1):51-60.
• [17] The novel azole R126638 is a selective inhibitor of ergosterol synthesis in Candida albicans, Trichophyton spp., and Microsporum canis. Antimicrob Agents Chemother. 2004 Sep;48(9):3272-8.
• [18] Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5.
• [19] Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity. Bioorg Med Chem Lett. 2004 Nov 15;14(22):5591-4.
• [20] Mechanism-based inactivation of CYP3A by HIV protease inhibitors. J Pharmacol Exp Ther. 2005 Feb;312(2):583-91.
• [21] Studies of the toxicological potential of capsinoids, XIII: inhibitory effects of capsaicin and capsinoids on cytochrome P450 3A4 in human liver microsomes. Int J Toxicol. 2010 Mar;29(2 Suppl):22S-6S.
• [22] Investigation of the effects of axitinib on the pharmacokinetics of loperamide and its main metabolite N-demethylated loperamide in rats by UPLC-MS/MS. Chem Biol Interact. 2019 Sep 1;310:108744. doi: 10.1016/j.cbi.2019.108744. Epub 2019 Jul 9.
• [23] Effect of organic anion-transporting polypeptide 1B1 (OATP1B1) polymorphism on the single- and multiple-dose pharmacokinetics of enalapril in healthy Chinese adult men. Clin Ther. 2011 May;33(5):655-63. doi: 10.1016/j.clinthera.2011.04.018.
• [24] Differential interaction of 3-hydroxy-3-methylglutaryl-coa reductase inhibitors with ABCB1, ABCC2, and OATP1B1. Drug Metab Dispos. 2005 Apr;33(4):537-46.
• [25] Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
• [26] Polymorphic organic anion transporting polypeptide 1B1 is a major determinant of repaglinide pharmacokinetics. Clin Pharmacol Ther. 2005 Jun;77(6):468-78. doi: 10.1016/j.clpt.2005.01.018.
• [27] SLC19A1, SLC46A1 and SLCO1B1 polymorphisms as predictors of methotrexate-related toxicity in Portuguese rheumatoid arthritis patients. Toxicol Sci. 2014 Nov;142(1):196-209. doi: 10.1093/toxsci/kfu162. Epub 2014 Aug 14.
• [28] SLCO1B1 variants and statin-induced myopathy--a genomewide study. N Engl J Med. 2008 Aug 21;359(8):789-99.
• [29] Transport of fluorescent chenodeoxycholic acid via the human organic anion transporters OATP1B1 and OATP1B3. J Lipid Res. 2006 Jun;47(6):1196-202.
• [30] Transcellular movement of hydroxyurea is mediated by specific solute carrier transporters. Exp Hematol. 2011 Apr;39(4):446-56.
• [31] Severe toxicities after irinotecan-based chemotherapy in a patient with lung cancer: a homozygote for the SLCO1B1*15 allele. Ther Drug Monit. 2007 Oct;29(5):666-8. doi: 10.1097/FTD.0b013e3181357364.