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

General Information of Drug (ID: DMH21D9)

• Drug Name: Ebastine Drug Info
• Synonyms: ebastine; Kestine; Ebastel; Ebastin; Evastel; Kestin; Bactil; Ebastinum [Latin]; LAS W-090; Ebastina [Spanish]; Estivan; UNII-TQD7Q784P1; RP 64305; 1-(4-tert-butylphenyl)-4-[4-(diphenylmethoxy)piperidin-1-yl]butan-1-one; TQD7Q784P1; CHEMBL305660; 4-Diphenylmethoxy-1-(3-(4-tert-butylbenzoyl)propyl)piperidine; C32H39NO2; MFCD00865661; 1-[4-(1,1-Dimethylethyl)phenyl]-4-[4-(diphenylmethoxy)-1-piperidinyl]-1-butanone; NCGC00164603-01; RP-64305; 4'-tert-Butyl-4-(4-(diphenylmethoxy)piperidino)butyrophenone
• Cross-matching ID:
  PubChem CID: 3191
  ChEBI ID: CHEMBL305660
  CAS Number: CAS 90729-43-4
  TTD Drug ID: DMH21D9
  VARIDT Drug ID: DR01688

Molecule-Related Drug Atlas

Drug(s) Transported By P-glycoprotein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[1]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[6]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[7]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[8]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[7]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[7]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[9]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[7]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[10]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[11]

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	[12]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[13]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[14]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[15]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[16]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[17]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[18]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[19]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[13]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[20]

Drug(s) Metabolized By Cytochrome P450 4F2 (CYP4F2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[21]
Fingolimod	DM5JVAN	Multiple sclerosis	8A40	Approved	[22]
Pafuramidine	DMFKOR9	Malaria	1F40-1F45	Phase 3	[23]
Tocopherol	DMBIJZ6	N. A.	N. A.	Phase 2	[24]
GSK618334	DMJPXZ4	Drug abuse	6C4G.1Z	Phase 1	[25]
Arachidonic Acid	DMUOQZD	Discovery agent	N.A.	Investigative	[26]

Drug(s) Metabolized By Cytochrome P450 2J2 (CYP2J2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Riociguat	DMXBLMP	Chronic thromboembolic pulmonary hypertension		Approved	[27]
Rivaroxaban	DMQMBZ1	Deep vein thrombosis	BD71	Approved	[28]
Ergocalciferol	DMHO0AR	Hypoparathyroidism	5A50	Approved	[29]
Vorapaxar	DMA16BR	Myocardial infarction	BA41-BA43	Approved	[30]
Vitamin D	DMWQUC9	N. A.	N. A.	Approved	[29]
Alfacalcidol	DM1237M	Hyperparathyroidism	5A51	Phase 4	[29]
MANIDIPINE	DMJPGUA	N. A.	N. A.	Phase 3	[31]
Carebastine	DMUVMWZ	Ocular allergy	4A81	Phase 3	[2]
Eperisone	DM1SMAI	Muscle spasm	MB47.3	Phase 3	[32]
H3B-6545	DMIFCY2	Breast cancer	2C60-2C65	Phase 1/2	[33]

Drug(s) Affected By Potassium voltage-gated channel subfamily A member 5 (KCNA5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bepridil	DM0RKS4	Chronic/stable angina	BA40.1	Approved	[34]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[35]
Pergolide mesylate	DM5GKOV	N. A.	N. A.	Approved	[36]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[37]
Decitabine	DMQL8XJ	Acute myelogenous leukaemia	2A41	Approved	[38]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[39]
Carbamazepine	DMZOLBI	Epilepsy	8A60-8A68	Approved	[37]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[40]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[40]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[40]

Molecular Interaction Atlas of This Drug

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[2]
Cytochrome P450 2J2 (CYP2J2)	DERSX5P	CP2J2_HUMAN	Substrate	[3]
Cytochrome P450 4F2 (CYP4F2)	DE3GT9C	CP4F2_HUMAN	Substrate	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Potassium voltage-gated channel subfamily A member 5 (KCNA5)	OTHI2N71	KCNA5_HUMAN	Gene/Protein Processing	[5]

References

• [1] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [2] Characterization of ebastine, hydroxyebastine, and carebastine metabolism by human liver microsomes and expressed cytochrome P450 enzymes: major roles for CYP2J2 and CYP3A. Drug Metab Dispos. 2006 Nov;34(11):1793-7.
• [3] Identifying a selective substrate and inhibitor pair for the evaluation of CYP2J2 activity. Drug Metab Dispos. 2012 May;40(5):943-51.
• [4] cDNA cloning and expression of a novel cytochrome p450 (cyp4f12) from human small intestine. Biochem Biophys Res Commun. 2001 Feb 2;280(4):1135-41.
• [5] Comparative effects of nonsedating histamine H1 receptor antagonists, ebastine and terfenadine, on human Kv1.5 channels. Eur J Pharmacol. 1997 May 20;326(2-3):257-63. doi: 10.1016/s0014-2999(97)85421-0.
• [6] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [7] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [8] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [9] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [10] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [11] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
• [12] 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.
• [13] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [14] 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.
• [15] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [16] 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.
• [17] 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.
• [18] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [19] 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.
• [20] 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.
• [21] Cloning and characterization of CYP4F21: a prostaglandin E2 20-hydroxylase of ram seminal vesicles. Arch Biochem Biophys. 2001 May 1;389(1):123-9.
• [22] CYP4F enzymes are responsible for the elimination of fingolimod (FTY720), a novel treatment of relapsing multiple sclerosis. Drug Metab Dispos. 2011 Feb;39(2):191-8.
• [23] Human enteric microsomal CYP4F enzymes O-demethylate the antiparasitic prodrug pafuramidine. Drug Metab Dispos. 2007 Nov;35(11):2067-75.
• [24] Discovery, characterization, and significance of the cytochrome P450 omega-hydroxylase pathway of vitamin E catabolism. Ann N Y Acad Sci. 2004 Dec;1031:13-21.
• [25] Product information - Gilenya.
• [26] Role of cytochrome P450 enzymes in the bioactivation of polyunsaturated fatty acids. Biochim Biophys Acta. 2011 Jan;1814(1):210-22.
• [27] Riociguat (adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. P T. 2014 Nov;39(11):749-58.
• [28] Comparative efficacy and safety of the novel oral anticoagulants dabigatran, rivaroxaban and apixaban in preclinical and clinical development. Thromb Haemost. 2010 Mar;103(3):572-85.
• [29] Characterization of rat and human CYP2J enzymes as Vitamin D 25-hydroxylases. Steroids. 2006 Oct;71(10):849-56.
• [30] Vorapaxar: the missing link in antiplatelet therapy! J Anaesthesiol Clin Pharmacol. 2017 Apr-Jun;33(2):269-270.
• [31] Inhibitory effects of antihypertensive drugs on human cytochrome P450 2J2 activity: Potent inhibition by azelnidipine and manidipine. Chem Biol Interact. 2019 Jun 1;306:1-9.
• [32] Characterization of human cytochrome P450 enzymes involved in the biotransformation of eperisone. Xenobiotica. 2009 Jan;39(1):1-10.
• [33] Nonclinical pharmacokinetics and in vitro metabolism of H3B-6545, a novel selective ERalpha covalent antagonist (SERCA). Cancer Chemother Pharmacol. 2019 Jan;83(1):151-160.
• [34] Inhibitory effect of bepridil on hKv1.5 channel current: comparison with amiodarone and E-4031. Eur J Pharmacol. 2001 Nov 2;430(2-3):149-57. doi: 10.1016/s0014-2999(01)01381-4.
• [35] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [36] Pergolide is an inhibitor of voltage-gated potassium channels, including Kv1.5, and causes pulmonary vasoconstriction. Circulation. 2005 Sep 6;112(10):1494-9. doi: 10.1161/CIRCULATIONAHA.105.556704. Epub 2005 Aug 29.
• [37] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [38] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [39] Differential effects of estrogen and progesterone on potassium channels expressed in Xenopus oocytes. Steroids. 2008 Mar;73(3):272-9. doi: 10.1016/j.steroids.2007.10.010. Epub 2007 Nov 4.
• [40] Detection of potassium currents and regulation of multidrug resistance by potassium channels in human gastric cancer cells. Cell Biol Int. 2007 Jul;31(7):741-7. doi: 10.1016/j.cellbi.2007.01.008. Epub 2007 Jan 21.