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

General Information of Drug (ID: DM0EP51)

• Drug Name: TAMARIXETIN Drug Info
• Synonyms: Tamarixetin; 603-61-2; 4'-Methoxyquercetin; 4'-O-Methylquercetin; Quercetin 4'-methyl ether; UNII-73WRA8Z8M8; 3,3',5,7-Tetrahydroxy-4'-methoxyflavone; 4'-O-Methyl Quercetin; Quercetin-4'-methylether; 73WRA8Z8M8; CHEMBL226034; CHEBI:67492; 3,5,7-Trihydroxy-2-(3-hydroxy-4-methoxyphenyl)-4-benzopyrone; 3,5,7-trihydroxy-2-(3-hydroxy-4-methoxyphenyl)-4H-chromen-4-one; 4'-Methoxy-3,3',5,7-tetrahydroxyflavone; Tamaraxetin; 3-O-rhamnopyranosyl-1-2-glucopyranoside; 3-O-alpha-L-rhamnopyranosyl-1-2-beta-D-glucopyranoside; AC1NQYX7

Indication

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

• Cross-matching ID:
  PubChem CID: 5281699
  ChEBI ID: CHEBI:67492
  CAS Number: CAS 603-61-2
  TTD Drug ID: DM0EP51

Molecule-Related Drug Atlas

Drug(s) Targeting Cytochrome P450 1B1 (CYP1B1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PINOCEMBRIN	DM96VWD	N. A.	N. A.	Phase 2	[1]
NARINGENIN	DMHAZLM	N. A.	N. A.	Phase 1	[1]
Chrysin	DM7V2LG	Discovery agent	N.A.	Investigative	[1]
APIGENIN	DMI3491	Discovery agent	N.A.	Investigative	[1]
KAEMPFEROL	DMHEMUB	Discovery agent	N.A.	Investigative	[1]
ISORHAMNETIN	DMQ4Z6E	Discovery agent	N.A.	Investigative	[1]
ACACETIN	DMQOB0X	Discovery agent	N.A.	Investigative	[1]
TRISMETHOXYRESVERATROL	DM6USPC	Discovery agent	N.A.	Investigative	[5]
Galangin	DM5TQ2O	Discovery agent	N.A.	Investigative	[1]
CHRYSOERIOL	DM96ECL	Discovery agent	N.A.	Investigative	[1]

Drug(s) Affected By Prostaglandin G/H synthase 2 (PTGS2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Hypertriglyceridemia	5C80.1	Approved	[6]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[7]
Gamolenic acid	DMQN30Z	Allergy	4A80-4A85	Approved	[8]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[9]
Flupentixol	DM0DJ9O	Schizophrenia	6A20	Approved	[10]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[11]
Ibandronate	DM0QZBN	Hypercalcaemia	5B91.0	Approved	[12]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[13]
Fexofenadine	DM17ONX	Allergic rhinitis	CA08.0	Approved	[14]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[15]

Drug(s) Affected By Cytochrome P450 1A2 (CYP1A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zolmitriptan	DM1IB4Q	Migraine	8A80	Approved	[16]
Rofecoxib	DM3P5DA	Osteoarthritis	FA00-FA05	Approved	[16]
Etoricoxib	DM6A4NW	Rheumatoid arthritis	FA20	Approved	[16]
Capsaicin	DMGMF6V	Back pain	ME84.Z	Approved	[17]
Hesperetin	DMKER83	High blood cholesterol level	5C80.00	Approved	[18]
Stiripentol	DMMSDOY	Dravet syndrome	8A61.11	Approved	[19]
Nifedipine	DMSVOZT	Angina pectoris	BA40	Approved	[20]
Zileuton	DMVRIC2	Allergic asthma	CA23.0	Approved	[21]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[22]
Clonidine	DM6RZ9Q	Attention deficit hyperactivity disorder	6A05.Z	Approved	[23]

Drug(s) Affected By ATP-dependent translocase ABCB1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Flupentixol	DM0DJ9O	Schizophrenia	6A20	Approved	[24]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[25]
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[26]
Lamotrigine	DM8SXYG	Bipolar disorder	6A60	Approved	[27]
Cepharanthine	DM9Y5JB	N. A.	N. A.	Approved	[28]
Itraconazole	DMCR1MV	Aspergillosis	1F20	Approved	[29]
Clozapine	DMFC71L	Schizophrenia	6A20	Approved	[30]
Midostaurin	DMI6E0R	Acute myeloid leukaemia	2A60	Approved	[31]
Trifluoperazine	DMKBYWI	Anxiety		Approved	[32]
Olanzapine	DMPFN6Y	Bipolar depression		Approved	[30]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Eplerenone	DMF0NQR	Heart failure	BD10-BD13	Approved	[33]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[34]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[35]
Voriconazole	DMAOL2S	Aspergillosis	1F20	Approved	[36]
Proguanil	DMBL79I	Malaria	1F40-1F45	Approved	[37]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[37]
Loratadine	DMF3AN7	Allergy	4A80-4A85	Approved	[38]
Nelfinavir mesylate	DMFX6G8	N. A.	N. A.	Approved	[39]
Capsaicin	DMGMF6V	Back pain	ME84.Z	Approved	[40]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[41]

Drug(s) Affected By Cytochrome P450 3A5 (CYP3A5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Eplerenone	DMF0NQR	Heart failure	BD10-BD13	Approved	[33]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[34]
Nelfinavir mesylate	DMFX6G8	N. A.	N. A.	Approved	[39]
Ritonavir	DMU764S	Human immunodeficiency virus infection	1C62	Approved	[39]
Ifosfamide	DMCT3I8	Adult central nervous system germ cell tumor		Approved	[42]
Omeprazole	DM471KJ	Cystic fibrosis	CA25	Approved	[43]
Thalidomide	DM70BU5	Adult T-cell leukemia/lymphoma		Approved	[44]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[45]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[46]
Hydrocortisone	DMGEMB7	Acne vulgaris	ED80	Approved	[47]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cytochrome P450 1B1 (CYP1B1)	TTI84H7	CP1B1_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Gene/Protein Processing	[2]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Gene/Protein Processing	[3]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Gene/Protein Processing	[2]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Gene/Protein Processing	[2]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Gene/Protein Processing	[4]

References

• [1] Selective inhibition of methoxyflavonoids on human CYP1B1 activity. Bioorg Med Chem. 2010 Sep 1;18(17):6310-5.
• [2] 3-Hydroxyflavone and structural analogues differentially activate pregnane X receptor: Implication for inflammatory bowel disease. Pharmacol Res. 2015 Oct;100:64-72.
• [3] Bioactive terpenoids and flavonoids from Ginkgo biloba extract induce the expression of hepatic drug-metabolizing enzymes through pregnane X receptor, constitutive androstane receptor, and aryl hydrocarbon receptor-mediated pathways. Pharm Res. 2009 Apr;26(4):872-82.
• [4] Characterisation of metabolites of the putative cancer chemopreventive agent quercetin and their effect on cyclo-oxygenase activity. Br J Cancer. 2004 Sep 13;91(6):1213-9.
• [5] Design, synthesis, and discovery of novel trans-stilbene analogues as potent and selective human cytochrome P450 1B1 inhibitors. J Med Chem. 2002 Jan 3;45(1):160-4.
• [6] Docosahexaenoic acid regulates gene expression in HUVEC cells treated with polycyclic aromatic hydrocarbons. Toxicol Lett. 2015 Jul 16;236(2):75-81.
• [7] Etoposide induces necrosis through p53-mediated antiapoptosis in human kidney proximal tubule cells. Toxicol Sci. 2015 Nov;148(1):204-19.
• [8] Conjugated linoleic acid, unlike other unsaturated fatty acids, strongly induces glutathione synthesis without any lipoperoxidation. Br J Nutr. 2006 Nov;96(5):811-9.
• [9] COX-2 and PPAR-gama confer cannabidiol-induced apoptosis of human lung cancer cells. Mol Cancer Ther. 2013 Jan;12(1):69-82.
• [10] Mitochondrial involvement in schizophrenia and other functional psychoses. Neurochem Res. 1996 Sep;21(9):995-1004.
• [11] Immunomodulatory effect of selective serotonin reuptake inhibitors (SSRIs) on human T lymphocyte function and gene expression. Eur Neuropsychopharmacol. 2007 Dec;17(12):774-80.
• [12] Stimulation of cyclooxygenase-2 expression by bone-derived transforming growth factor-beta enhances bone metastases in breast cancer. Cancer Res. 2006 Feb 15;66(4):2067-73.
• [13] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [14] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [15] A2E selectively induces cox-2 in ARPE-19 and human neural cells. Curr Eye Res. 2006 Mar;31(3):259-63.
• [16] In vitro inhibition of CYP1A2 by model inhibitors, anti-inflammatory analgesics and female sex steroids: predictability of in vivo interactions. Basic Clin Pharmacol Toxicol. 2008 Aug;103(2):157-65.
• [17] Effects of capsaicin and dihydrocapsaicin on human and rat liver microsomal CYP450 enzyme activities in vitro and in vivo. J Asian Nat Prod Res. 2012;14(4):382-95.
• [18] Drug interaction study of flavonoids toward CYP3A4 and their quantitative structure activity relationship (QSAR) analysis for predicting potential effects. Toxicol Lett. 2018 Sep 15;294:27-36.
• [19] Stiripentol. Expert Opin Investig Drugs. 2005 Jul;14(7):905-11.
• [20] Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol. 2000 Feb-Mar;55(11-12):843-52.
• [21] Mechanism-based inhibition of human liver microsomal cytochrome P450 1A2 by zileuton, a 5-lipoxygenase inhibitor. Drug Metab Dispos. 2003 Nov;31(11):1352-60.
• [22] Predictive three-dimensional quantitative structure-activity relationship of cytochrome P450 1A2 inhibitors. J Med Chem. 2005 Jun 2;48(11):3808-15.
• [23] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [24] Characteristics of P388/VMDRC.04, a simple, sensitive model for studying P-glycoprotein antagonists. Cancer Res. 1994 Feb 1;54(3):730-7.
• [25] Michaelis-Menten kinetic analysis of drugs of abuse to estimate their affinity to human P-glycoprotein. Toxicol Lett. 2013 Feb 27;217(2):137-42. doi: 10.1016/j.toxlet.2012.12.012. Epub 2012 Dec 27.
• [26] Editor's Highlight: PlacentalDisposition and Effects of Crizotinib: An Ex Vivo Study in the Isolated Dual-Side Perfused Human Cotyledon. Toxicol Sci. 2017 Jun 1;157(2):500-509. doi: 10.1093/toxsci/kfx063.
• [27] Functional evaluation of polymorphisms in the human ABCB1 gene and the impact on clinical responses of antiepileptic drugs. Pharmacogenet Genomics. 2008 May;18(5):390-402. doi: 10.1097/FPC.0b013e3282f85e36.
• [28] Cepharanthine potently enhances the sensitivity of anticancer agents in K562 cells. Cancer Sci. 2005 Jun;96(6):372-6. doi: 10.1111/j.1349-7006.2005.00057.x.
• [29] Clinical pharmacokinetic monitoring of itraconazole is warranted in only a subset of patients. Ther Drug Monit. 2005 Jun;27(3):322-33. doi: 10.1097/01.ftd.0000150135.22645.ea.
• [30] Evaluation of antipsychotic drugs as inhibitors of multidrug resistance transporter P-glycoprotein. Psychopharmacology (Berl). 2006 Sep;187(4):415-23. doi: 10.1007/s00213-006-0437-9. Epub 2006 Jun 30.
• [31] Actions of the selective protein kinase C inhibitor PKC412 on B-chronic lymphocytic leukemia cells in vitro. Haematologica. 2002 Feb;87(2):167-76.
• [32] Characterization of the ATPase activity of the Mr 170,000 to 180,000 membrane glycoprotein (P-glycoprotein) associated with multidrug resistance in K562/ADM cells. Cancer Res. 1988 Sep 1;48(17):4926-32.
• [33] The relative role of CYP3A4 and CYP3A5 in eplerenone metabolism. Toxicol Lett. 2019 Oct 15;315:9-13.
• [34] 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.
• [35] 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.
• [36] 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.
• [37] 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.
• [38] Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity. Bioorg Med Chem Lett. 2004 Nov 15;14(22):5591-4.
• [39] Mechanism-based inactivation of CYP3A by HIV protease inhibitors. J Pharmacol Exp Ther. 2005 Feb;312(2):583-91.
• [40] 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.
• [41] 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.
• [42] Contribution of CYP3A5 to hepatic and renal ifosfamide N-dechloroethylation. Drug Metab Dispos. 2005 Jul;33(7):1074-81. doi: 10.1124/dmd.104.002279. Epub 2005 Apr 8.
• [43] Use of mRNA expression to detect the induction of drug metabolising enzymes in rat and human hepatocytes. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):86-96.
• [44] Induction of human cytochrome P450 3A enzymes in cultured placental cells by thalidomide and relevance to bioactivation and toxicity. J Toxicol Sci. 2017;42(3):343-348.
• [45] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [46] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [47] Induction of hepatic CYP3A enzymes by pregnancy-related hormones: studies in human hepatocytes and hepatic cell lines. Drug Metab Dispos. 2013 Feb;41(2):281-90.