General Information of Drug Combination (ID: DCXE3NQ)

Drug Combination Name
Rebamipide Lansoprazole
Indication
Disease Entry Status REF
Gastroesophageal Reflux Phase 4 [1]
Component Drugs Rebamipide   DM2GHCR Lansoprazole   DMXYLQ3
Small molecular drug N.A.
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Rebamipide
Disease Entry ICD 11 Status REF
Peptic ulcer DA61 Phase 3 [2]
Rebamipide Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
N-formyl peptide receptor (FPR1) TT5Y4EM FPR1_HUMAN Antagonist [5]
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Rebamipide Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [6]
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Rebamipide Interacts with 11 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [7]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Decreases Expression [4]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Decreases Expression [8]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Increases Expression [4]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [4]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [4]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Increases Expression [4]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Decreases Expression [4]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Increases Expression [4]
Aurora kinase B (AURKB) OTIY4VHU AURKB_HUMAN Decreases Expression [7]
ATP-binding cassette sub-family C member 4 (ABCC4) OTO27PAL MRP4_HUMAN Increases Transport [9]
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⏷ Show the Full List of 11 DOT(s)
Indication(s) of Lansoprazole
Disease Entry ICD 11 Status REF
Gastric ulcer DA60 Approved [3]
Gastrinoma 2C10.1 Approved [3]
Peptic ulcer DA61 Approved [3]
Lansoprazole Interacts with 5 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
Cytochrome P450 2C18 (CYP2C18) DEZMWRE CP2CI_HUMAN Metabolism [11]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [12]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [13]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [14]
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Lansoprazole Interacts with 24 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [15]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Increases Hydroxylation [16]
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Increases Hydroxylation [12]
Cytochrome P450 2C18 (CYP2C18) OTY687L9 CP2CI_HUMAN Increases Hydroxylation [11]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Affects Response To Substance [17]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Expression [15]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Increases Expression [18]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Increases Expression [18]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Activity [19]
Phospholipid-transporting ATPase ABCA1 (ABCA1) OT94G6BQ ABCA1_HUMAN Increases Expression [20]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Increases Expression [21]
Protransforming growth factor alpha (TGFA) OTPD1LL9 TGFA_HUMAN Increases Expression [21]
Pro-opiomelanocortin (POMC) OTV41F7T COLI_HUMAN Increases Expression [22]
Gastrin (GAST) OTD0IP9N GAST_HUMAN Increases Expression [23]
Apolipoprotein E (APOE) OTFOWL2H APOE_HUMAN Increases Expression [20]
Fibroblast growth factor 2 (FGF2) OT7YUJ9F FGF2_HUMAN Decreases Expression [21]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [24]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Decreases Expression [25]
Microtubule-associated protein tau (MAPT) OTMTP2Z7 TAU_HUMAN Affects Binding [26]
Oxysterols receptor LXR-beta (NR1H2) OT4APA60 NR1H2_HUMAN Increases Activity [20]
Hepcidin (HAMP) OT607RBL HEPC_HUMAN Increases Expression [27]
Oxysterols receptor LXR-alpha (NR1H3) OT54YZ9I NR1H3_HUMAN Increases Activity [20]
Phosphoethanolamine/phosphocholine phosphatase (PHOSPHO1) OT43A0JA PHOP1_HUMAN Decreases Activity [28]
Fibroblast growth factor 21 (FGF21) OT3RXVRD FGF21_HUMAN Increases Expression [29]
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⏷ Show the Full List of 24 DOT(s)

References

1 ClinicalTrials.gov (NCT02755753) A Study to Evaluate REbamiPide as an Adjuvant Regimen to Heal erosIve Reflux Esophagitis
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: 871).
3 Lansoprazole FDA Label
4 Rebamipide suppresses 5-fluorouracil-induced cell death via the activation of Akt/mTOR pathway and regulates the expression of Bcl-2 family proteins. Toxicol In Vitro. 2018 Feb;46:284-293. doi: 10.1016/j.tiv.2017.10.019. Epub 2017 Oct 17.
5 Rebamipide suppresses formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide production by inhibiting fMLP-receptor binding in human neutrophils. J Pharmacol Exp Ther. 2001 Apr;297(1):388-94.
6 Involvement of cytochrome P450 in the metabolism of rebamipide by the human liver. Xenobiotica. 2002 Jul;32(7):573-86.
7 Rebamipide inhibits gastric cancer growth by targeting survivin and Aurora-B. Biochem Biophys Res Commun. 2005 Aug 19;334(1):207-12. doi: 10.1016/j.bbrc.2005.05.204.
8 Management of recurrence of symptoms of gastroesophageal reflux disease: synergistic effect of rebamipide with 15 mg lansoprazole. Dig Dis Sci. 2010 Dec;55(12):3393-8. doi: 10.1007/s10620-010-1166-9. Epub 2010 Mar 3.
9 Multichannel liquid chromatography-tandem mass spectrometry cocktail method for comprehensive substrate characterization of multidrug resistance-associated protein 4 transporter. Pharm Res. 2007 Dec;24(12):2281-96.
10 An evaluation of the cytochrome P450 induction potential of pantoprazole in primary human hepatocytes. Chem Biol Interact. 1998 Jul 3;114(1-2):1-13.
11 Oxidative metabolism of lansoprazole by human liver cytochromes P450. Mol Pharmacol. 1995 Feb;47(2):410-8.
12 Identification of the human P450 enzymes involved in lansoprazole metabolism. J Pharmacol Exp Ther. 1996 May;277(2):805-16.
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 Effects of clarithromycin on lansoprazole pharmacokinetics between CYP2C19 genotypes. Br J Clin Pharmacol. 2005 Mar;59(3):302-9.
15 Measurement of cytochrome P450 gene induction in human hepatocytes using quantitative real-time reverse transcriptase-polymerase chain reaction. Drug Metab Dispos. 2000 Jul;28(7):781-8.
16 Stereoselective metabolism of lansoprazole by human liver cytochrome P450 enzymes. Drug Metab Dispos. 2003 Oct;31(10):1227-34.
17 Effect of MDR1 C3435T polymorphism on lansoprazole in healthy Japanese subjects. Eur J Clin Pharmacol. 2009 Jun;65(6):593-600. doi: 10.1007/s00228-009-0625-8. Epub 2009 Feb 24.
18 Time-dependent transcriptional induction of CYP1A1, CYP1A2 and CYP1B1 mRNAs by H+/K+ -ATPase inhibitors and other xenobiotics. Xenobiotica. 2003 Feb;33(2):107-18.
19 Screening of a chemical library reveals novel PXR-activating pharmacologic compounds. Toxicol Lett. 2015 Jan 5;232(1):193-202. doi: 10.1016/j.toxlet.2014.10.009. Epub 2014 Oct 16.
20 Proton pump inhibitor lansoprazole is a nuclear liver X receptor agonist. Biochem Pharmacol. 2010 May 1;79(9):1310-6. doi: 10.1016/j.bcp.2009.12.018. Epub 2010 Jan 8.
21 Effect of chronic duodenal ulceration and its treatment with lanzoprazole or sucralfate on gastroduodenal mucosal protein turnover and TGF-alpha, bFGF, and EGF receptor expression in humans. Dig Dis Sci. 1998 Dec;43(12):2764-70. doi: 10.1023/a:1026680017329.
22 Comparison of the effects of proton pump inhibitors on human plasma adrenocorticotropic hormone and cortisol levels under the starved condition. Biomed Pharmacother. 2006 Apr;60(3):109-12. doi: 10.1016/j.biopha.2006.01.004. Epub 2006 Feb 21.
23 Influence of lansoprazole on intragastric 24-hour pH, meal-stimulated gastric acid secretion, and concentrations of gastrointestinal hormones and enzymes in serum and gastric juice in healthy volunteers. Digestion. 1995;56(2):137-44. doi: 10.1159/000201233.
24 Beyond gastric acid reduction: proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells. Biochem Biophys Res Commun. 2006 Jul 7;345(3):1014-21. doi: 10.1016/j.bbrc.2006.04.170. Epub 2006 May 6.
25 Enhanced expression of interleukin-8 and activation of nuclear factor kappa-B in endoscopy-negative gastroesophageal reflux disease. Am J Gastroenterol. 2004 Apr;99(4):589-97. doi: 10.1111/j.1572-0241.2004.04110.x.
26 Selective interaction of lansoprazole and astemizole with tau polymers: potential new clinical use in diagnosis of Alzheimer's disease. J Alzheimers Dis. 2010;19(2):573-89. doi: 10.3233/JAD-2010-1262.
27 Proton pump inhibitors block iron absorption through direct regulation of hepcidin via the aryl hydrocarbon receptor-mediated pathway. Toxicol Lett. 2020 Jan;318:86-91. doi: 10.1016/j.toxlet.2019.10.016. Epub 2019 Oct 24.
28 Functional involvement of PHOSPHO1 in matrix vesicle-mediated skeletal mineralization. J Bone Miner Res. 2007 Apr;22(4):617-27. doi: 10.1359/jbmr.070108.
29 Increased immunoreactivity and concentration of basic fibroblast growth factor in lansoprazole-treated gastric mucosa. J Clin Gastroenterol. 1995;21 Suppl 1:S24-9.