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

General Information of Drug (ID: DM1DBV5)

• Drug Name: Dexlansoprazole Drug Info
• Synonyms: dexlansoprazole; (R)-Lansoprazole; 138530-94-6; Kapidex; dexilant; R-(+)-LANSOPRAZOLE; Dexilant Solutab; TAK 390; UNII-UYE4T5I70X; TAK-390; (r)-(+)-lansoprazole; T 168390; UYE4T5I70X; AK170558; TAK-390MR; T-168390; 2-((R)-((3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl)methyl)sulfinyl)-1H-benzimidazole; 2-[(R)-[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methylsulfinyl]-1H-benzimidazole; (R)-2-(((3-Methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazole; Dexlansoprazole (INN/USAN); Kapidex; KS-1075; Lansoprazole

Indication

Disease Entry	ICD 11	Status	REF
Erosive esophagitis	DA25.0	Approved	[1]
Non-erosive gastro-esophageal reflux disease	DA22.0	Approved	[1]
Peptic ulcer	DA61	Approved	[2]
NSAID-associated gastric ulcer	DA60	Phase 3	[2]

• Cross-matching ID:
  PubChem CID: 9578005
  ChEBI ID: CHEBI:135931
  CAS Number: CAS 138530-94-6
  TTD Drug ID: DM1DBV5
  VARIDT Drug ID: DR00643
  INTEDE Drug ID: DR0469
  ACDINA Drug ID: D00187

Molecule-Related Drug Atlas

Drug(s) Targeting Gastric H(+)/K(+) ATPase alpha (ATP4A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Rabeprazole	DMMZXIW	Bacterial infection	1A00-1C4Z	Approved	[8]
AG-SPT201	DMJRQDG	Ulcerative colitis	DD71	Phase 3	[9]
API-023	DM6P93J	Gastroesophageal reflux disease	DA22.Z	Phase 1	[10]
Saliphenylhalamide	DMLMRGH	Solid tumour/cancer	2A00-2F9Z	Preclinical	[10]
PA-10040	DMELTM2	Cardiovascular disease	BA00-BE2Z	Investigative	[10]
CA-50040	DMCLN6M	Colorectal cancer	2B91.Z	Investigative	[10]
ARH-1029	DM8NETP	Helicobacter infection	DA42-DA63	Investigative	[10]
OPC-22575	DMO4WH9	Ulcerative colitis	DD71	Investigative	[10]
CDRI-85/92	DMQDA5W	Stomach ulcer	DA60.Z	Investigative	[10]

Drug(s) Targeting Gastric H(+)/K(+) ATPase (Proton pump)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Omeprazole	DM471KJ	Cystic fibrosis	CA25	Approved	[3]
Pantoprazole	DMSVOCZ	Gastrinoma	2C10.1	Approved	[3]
Esomeprazole	DM7BN0X	Cystic fibrosis	CA25	Approved	[3]
Vonoprazan	DMO6315	Helicobacter infection	DA42-DA63	Approved	[11]
RQ-00000004	DM9T8OF	Gastroesophageal reflux disease	DA22.Z	Phase 3	[12]
YH-4808	DMCHFB0	Duodenal ulcer	DA63	Phase 2	[13]
S-tenatoprazole	DMJ1DIB	Peptic ulcer	DA61	Phase 2	[14]
AZD-0865	DMM0N1F	Gastrointestinal disease	DE2Z	Phase 2	[15]
LEMINOPRAZOLE	DMBKNJT	Ulcerative colitis	DD71	Discontinued in Preregistration	[16]
SKF-96067	DMXW1Y3	Peptic ulcer	DA61	Discontinued in Phase 3	[17]

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	[18]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[19]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[20]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[21]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[20]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[20]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[22]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[20]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[23]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[24]

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	[25]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[26]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[27]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[28]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[29]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[30]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[31]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[32]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[26]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[33]

Drug(s) Metabolized By Mephenytoin 4-hydroxylase (CYP2C19)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[34]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[35]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[36]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[37]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[38]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[39]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[40]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[41]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[42]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[43]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Gastric H(+)/K(+) ATPase (Proton pump)	TTLOKXP	ATP4A_HUMAN; ATP4B_HUMAN	Modulator	[3]
Gastric H(+)/K(+) ATPase alpha (ATP4A)	TTF1QVM	ATP4A_HUMAN	Inhibitor	[4]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[6]
Mephenytoin 4-hydroxylase (CYP2C19) Main DME	DEGTFWK	CP2CJ_HUMAN	Substrate	[7]

References

• [1] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 022287.
• [2] 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: 7208).
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] Clinical pipeline report, company report or official report of Takeda (2009).
• [5] A novel screening strategy to identify ABCB1 substrates and inhibitors. Naunyn Schmiedebergs Arch Pharmacol. 2009 Jan;379(1):11-26.
• [6] Absorption, distribution, metabolism and excretion of [14C]dexlansoprazole in healthy male subjects. Clin Drug Investig. 2012 May 1;32(5):319-32.
• [7] Pharmacological and safety profile of dexlansoprazole: a new proton pump inhibitor - implications for treatment of gastroesophageal reflux disease in the Asia Pacific region. J Neurogastroenterol Motil. 2016 Jul 30;22(3):355-66.
• [8] Review article: rabeprazole's tolerability profile in clinical trials. Aliment Pharmacol Ther. 1999 Oct;13 Suppl 5:17-23.
• [9] Effects of pantoprazole, a novel H+/K+-ATPase inhibitor, on duodenal ulcerogenic and healing responses in rats: a comparative study with omeprazole and lansoprazole. J Gastroenterol Hepatol. 1999 Mar;14(3):251-7.
• [10] 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. (Target id: 849).
• [11] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2008
• [12] N-(2-hydroxyethyl)-N,2-dimethyl-8-{[(4R)-5-methyl-3,4-dihydro-2H-chromen-4-yl]amino}imidazo[1,2-a]pyridine-6-carboxamide (PF-03716556), a novel, potent, and selective acid pump antagonist for the treatment of gastroesophageal reflux disease. J Pharmacol Exp Ther. 2009 Feb;328(2):671-9.
• [13] Poor effectiveness of proton pump inhibitors in non-erosive reflux disease: the truth in the end! Neurogastroenterol Motil.2012 Aug;24(8):697-704.
• [14] Tenatoprazole, a novel proton pump inhibitor with a prolonged plasma half-life: effects on intragastric pH and comparison with esomeprazole in heal... Aliment Pharmacol Ther. 2004 Mar 15;19(6):655-62.
• [15] Mechanism of action of AZD0865, a K+-competitive inhibitor of gastric H+,K+-ATPase. Biochem Pharmacol. 2007 Jan 15;73(2):198-205.
• [16] Vasoinhibitory effect of leminoprazole, a H+,K(+)-ATPase inhibitor, on rat aortic rings. Gen Pharmacol. 1996 Jan;27(1):117-21.
• [17] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [18] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [19] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [20] 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.
• [21] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [22] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [23] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [24] 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.
• [25] 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.
• [26] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [27] 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.
• [28] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [29] 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.
• [30] 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.
• [31] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [32] 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.
• [33] 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.
• [34] High-dose rabeprazole/amoxicillin therapy as the second-line regimen after failure to eradicate H. pylori by triple therapy with the usual doses of a proton pump inhibitor, clarithromycin and amoxicillin. Hepatogastroenterology. 2003 Nov-Dec;50(54):2274-8.
• [35] Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
• [36] Cytochrome P450 pharmacogenetics and cancer. Oncogene. 2006 Mar 13;25(11):1679-91.
• [37] CYP2C19*17 is associated with decreased breast cancer risk. Breast Cancer Res Treat. 2009 May;115(2):391-6.
• [38] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [39] Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):116-21.
• [40] Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70.
• [41] A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
• [42] Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33.
• [43] Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.