General Information of Drug Combination (ID: DCK6IOU)

Drug Combination Name
Clarithromycin Vonoprazan
Indication
Disease Entry Status REF
Helicobacter Pylori Infection Phase 3 [1]
Component Drugs Clarithromycin   DM4M1SG Vonoprazan   DMO6315
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Clarithromycin
Disease Entry ICD 11 Status REF
Acute maxillary sinusitis N.A. Approved [2]
Acute otitis media AB00 Approved [2]
Bacterial infection 1A00-1C4Z Approved [3]
Mycoplasma pneumoniae pneumonia N.A. Approved [2]
Staphylococcus aureus infection N.A. Approved [2]
Streptococcal pneumonia N.A. Approved [2]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [4]
Pneumonia caused by chlamydia N.A. Investigative [2]
Clarithromycin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bacterial 50S ribosomal RNA (Bact 50S rRNA) TTUWYEA NOUNIPROTAC Binder [7]
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Clarithromycin Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]
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Clarithromycin Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [9]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [10]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [11]
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Clarithromycin Interacts with 15 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Decreases Expression [12]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [13]
Phytanoyl-CoA dioxygenase, peroxisomal (PHYH) OTUG4BWA PAHX_HUMAN Decreases Expression [14]
Lanosterol synthase (LSS) OT9W2SFH LSS_HUMAN Decreases Expression [14]
Inhibin beta E chain (INHBE) OTOI2NYG INHBE_HUMAN Increases Expression [14]
Acid ceramidase (ASAH1) OT1DNGXL ASAH1_HUMAN Increases Expression [14]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [15]
Cytochrome c oxidase subunit 2 (COX2) OTTMVBJJ COX2_HUMAN Decreases Expression [16]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Increases Expression [17]
Interleukin-4 (IL4) OTOXBWAU IL4_HUMAN Decreases Expression [18]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [19]
Integrin beta-4 (ITGB4) OT28UK84 ITB4_HUMAN Decreases Expression [20]
Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1) OT8SPJNX KCNQ1_HUMAN Increases ADR [21]
Translation initiation factor IF-2, mitochondrial (MTIF2) OTAIOZ0J IF2M_HUMAN Decreases Response To Substance [16]
Misshapen-like kinase 1 (MINK1) OTKB0RA8 MINK1_HUMAN Increases ADR [21]
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⏷ Show the Full List of 15 DOT(s)
Indication(s) of Vonoprazan
Disease Entry ICD 11 Status REF
Helicobacter infection DA42-DA63 Approved [5]
Gastroesophageal reflux disease DA22.Z Phase 3 [6]
Vonoprazan Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Gastric H(+)/K(+) ATPase (Proton pump) TTLOKXP ATP4A_HUMAN; ATP4B_HUMAN Modulator [5]
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Vonoprazan Interacts with 5 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [22]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [22]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [22]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [22]
Sulfotransferase 2A1 (SULT2A1) DE0P6LK ST2A1_HUMAN Metabolism [22]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Treatment Effectiveness DCSNZ5N N. A. Phase 3 [23]
Gastric/Duodenal Ulcer, Gastric MALT Lymphoma, Idiopathic Thrombocytopenic Purpura, or H. Pylori Gastritis, and Other DC23ZIF N. A. Phase 2 [24]
Helicobacter Pylori DC52MW8 N. A. Phase 1 [25]
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References

1 ClinicalTrials.gov (NCT04167670) Efficacy and Safety of Vonoprazan Compared to Lansoprazole in Participants With Helicobacter Pylori Infection
2 Clarithromycin FDA Label
3 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
4 Anti-inflammatory Clarithromycin for Improving COVID-19 Infection Early (ACHIEVE)
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2008
6 ClinicalTrials.gov (NCT02388724) Efficacy and Safety of Oral Once-Daily Vonoprazan (TAK-438) in Patients With Erosive Esophagitis. U.S. National Institutes of Health.
7 Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria. Nature. 2001 Oct 25;413(6858):814-21.
8 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.
9 Pharmacokinetic variability of clarithromycin and differences in CYP3A4 activity in patients with cystic fibrosis. J Cyst Fibros. 2014 Mar;13(2):179-85.
10 Drug Interactions Flockhart Table
11 Influence of CYP2C19 polymorphism and Helicobacter pylori genotype determined from gastric tissue samples on response to triple therapy for H pylori infection. Clin Gastroenterol Hepatol. 2005 Jun;3(6):564-73.
12 Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction. Drug Metab Dispos. 2006 Oct;34(10):1742-8.
13 Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.
14 A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system. Toxicol Sci. 2005 Feb;83(2):282-92.
15 Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
16 A genome-wide analysis of targets of macrolide antibiotics in mammalian cells. J Biol Chem. 2020 Feb 14;295(7):2057-2067. doi: 10.1074/jbc.RA119.010770. Epub 2020 Jan 8.
17 Liver toxicity of macrolide antibiotics in zebrafish. Toxicology. 2020 Aug;441:152501. doi: 10.1016/j.tox.2020.152501. Epub 2020 May 23.
18 Differential effects of three antibiotics on T helper cell cytokine expression. J Antimicrob Chemother. 2005 Sep;56(3):502-6. doi: 10.1093/jac/dki251. Epub 2005 Jul 8.
19 T-cell involvement in drug-induced acute generalized exanthematous pustulosis. J Clin Invest. 2001 Jun;107(11):1433-41. doi: 10.1172/JCI12118.
20 Effects of eight antibacterial agents on cell survival and expression of epithelial-cell- or cell-adhesion-related genes in human gingival epithelial cells. J Periodontal Res. 2004 Feb;39(1):50-8. doi: 10.1111/j.1600-0765.2004.00704.x.
21 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.
22 In vitro metabolism of TAK-438, vonoprazan fumarate, a novel potassium-competitive acid blocker. Xenobiotica. 2017 Dec;47(12):1027-1034.
23 ClinicalTrials.gov (NCT06162949) Vonoprazan for Helicobacter Pylori Eradication in Adolescents
24 ClinicalTrials.gov (NCT03219723) Drug Use Surveillance of Takecab for "Supplement to Helicobacter Pylori Eradication"
25 ClinicalTrials.gov (NCT04753437) A Study of Vonoprazan in Adults With Helicobacter Pylori