General Information of Drug Combination (ID: DCZRGBK)

Drug Combination Name
Ezetimibe Mycophenolic acid
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Ezetimibe   DM7A8TW Mycophenolic acid   DMRBMAU
Small molecular drug N.A.
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 2.99
Bliss Independence Score: 2.99
Loewe Additivity Score: 3.78
LHighest Single Agent (HSA) Score: 3.78

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Ezetimibe
Disease Entry ICD 11 Status REF
Atherosclerosis BD40 Approved [2]
Hypercholesterolaemia 5C80.0 Approved [3]
Hyperlipidemia 5C80.Z Approved [2]
Hyperlipidemia, familial combined, LPL related N.A. Approved [2]
Non-alcoholic fatty liver disease DB92 Approved [2]
Type-1/2 diabetes 5A10-5A11 Approved [2]
Ezetimibe Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Niemann-Pick C1-like protein 1 (NPC1L1) TTPD1CN NPCL1_HUMAN Inhibitor [16]
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Ezetimibe Interacts with 6 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [17]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [18]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [19]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [20]
Multidrug resistance-associated protein 3 (ABCC3) DTQ3ZHF MRP3_HUMAN Substrate [19]
Bile salt export pump (ABCB11) DTJ0EW4 ABCBB_HUMAN Substrate [21]
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⏷ Show the Full List of 6 DTP(s)
Ezetimibe 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]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [22]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DEB3CV1 UD2B7_HUMAN Metabolism [22]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DEF2WXN UD13_HUMAN Metabolism [23]
UDP-glucuronosyltransferase 2B15 (UGT2B15) DENZ6B1 UDB15_HUMAN Metabolism [22]
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Ezetimibe Interacts with 9 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [21]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) OTRT3F3U HMDH_HUMAN Increases Activity [24]
Phospholipid-transporting ATPase ABCA1 (ABCA1) OT94G6BQ ABCA1_HUMAN Decreases Expression [25]
Retinoic acid receptor gamma (RARG) OT8LHMDH RARG_HUMAN Decreases Expression [25]
Sterol regulatory element-binding protein 1 (SREBF1) OTWBRPAI SRBP1_HUMAN Decreases Expression [25]
Oxysterols receptor LXR-beta (NR1H2) OT4APA60 NR1H2_HUMAN Decreases Expression [25]
Sterol regulatory element-binding protein 2 (SREBF2) OTBXUNPL SRBP2_HUMAN Decreases Expression [25]
Scavenger receptor class B member 1 (SCARB1) OTAE1UA1 SCRB1_HUMAN Decreases Expression [25]
NPC1-like intracellular cholesterol transporter 1 (NPC1L1) OT6GWW1P NPCL1_HUMAN Decreases Response To Substance [26]
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⏷ Show the Full List of 9 DOT(s)
Indication(s) of Mycophenolic acid
Disease Entry ICD 11 Status REF
Crohn disease DD70 Approved [4]
Hepatosplenic T-cell lymphoma N.A. Approved [5]
Interstitial cystitis GC00.3 Approved [6]
Large granular lymphocytic leukemia 2A90.1 Approved [5]
Leukemia N.A. Approved [7]
Lupus nephritis 4A40.0Y Approved [8]
MALT lymphoma N.A. Approved [5]
Myeloid leukaemia 2B33.1 Approved [9]
Myeloproliferative neoplasm 2A20 Approved [10]
Nodal marginal zone lymphoma 2A85.0 Approved [5]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [5]
Recurrent adult burkitt lymphoma 2A85.6 Approved [5]
Small intestine lymphoma N.A. Approved [5]
Splenic marginal zone lymphoma N.A. Approved [5]
Systemic lupus erythematosus 4A40.0 Approved [11]
Testicular lymphoma N.A. Approved [5]
Classic Hodgkin lymphoma N.A. Investigative [12]
Coronavirus Disease 2019 (COVID-19) 1D6Y Investigative [13]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [14]
Mycophenolic acid Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
MERS-CoV papain-like proteinase (PL-PRO) TTYJOLE R1AB_CVEMC (854-2740) Inhibitor [14]
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Mycophenolic acid Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [27]
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [28]
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Mycophenolic acid Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
UDP-glucuronosyltransferase 2B7 (UGT2B7) DEB3CV1 UD2B7_HUMAN Metabolism [29]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Metabolism [29]
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References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 Ezetimibe FDA Label
3 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: 6816).
4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
5 A standard database for drug repositioning. Sci Data. 2017 Mar 14;4:170029.
6 Early termination of a trial of mycophenolate mofetil for treatment of interstitial cystitis/painful bladder syndrome: lessons learned. J Urol. 2011 Mar;185(3):901-6.
7 New conjugates of mycophenolic acid and their antiproliferative activity. J Asian Nat Prod Res. 2016 Nov;18(11):1057-62.
8 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis. 2020 Jun;79(6):713-723.
9 Mycophenolic Acid overcomes imatinib and nilotinib resistance of chronic myeloid leukemia cells by apoptosis or a senescent-like cell cycle arrest. Leuk Res Treatment. 2012;2012:861301.
10 Thiotepa, Busulfan, and Fludarabine Conditioning Regimen in T Cell-Replete HLA-Haploidentical Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2019 Jul;25(7):1407-1415.
11 Systemic Lupus Erythematosus Management in Pregnancy. Int J Womens Health. 2022 Feb 15;14:199-211.
12 Identification of potential drugs for diffuse large b-cell lymphoma based on bioinformatics and Connectivity Map database. Pathol Res Pract. 2018 Nov;214(11):1854-1867.
13 Associations between immune-suppressive and stimulating drugs and novel COVID-19-a systematic review of current evidence. Ecancermedicalscience. 2020 Mar 27;14:1022.
14 SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016 Aug;14(8):523-34.
15 Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of ezetimibe (Zetia). Drug Metab Dispos. 2004 Mar;32(3):314-20.
16 Update on patented cholesterol absorption inhibitors. Expert Opin Ther Pat. 2009 Aug;19(8):1083-107.
17 Intestinal expression of P-glycoprotein (ABCB1), multidrug resistance associated protein 2 (ABCC2), and uridine diphosphate-glucuronosyltransferase 1A1 predicts the disposition and modulates the effects of the cholesterol absorption inhibitor ezetimibe in humans. Clin Pharmacol Ther. 2006 Mar;79(3):206-17.
18 Pharmacokinetic and pharmacodynamic interactions between the immunosuppressant sirolimus and the lipid-lowering drug ezetimibe in healthy volunteers. Clin Pharmacol Ther. 2010 Jun;87(6):663-7.
19 Complex pharmacokinetic behavior of ezetimibe depends on abcc2, abcc3, and abcg2. Drug Metab Dispos. 2009 Aug;37(8):1698-702.
20 A LC-MS/MS method to quantify the novel cholesterol lowering drug ezetimibe in human serum, urine and feces in healthy subjects genotyped for SLCO1B1. J Chromatogr B Analyt Technol Biomed Life Sci. 2006 Jan 2;830(1):143-50.
21 Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
22 Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-94.
23 Drug interactions between the immunosuppressant tacrolimus and the cholesterol absorption inhibitor ezetimibe in healthy volunteers. Clin Pharmacol Ther. 2011 Apr;89(4):524-8.
24 Effects of ezetimibe and/or simvastatin on LDL receptor protein expression and on LDL receptor and HMG-CoA reductase gene expression: a randomized trial in healthy men. Atherosclerosis. 2008 May;198(1):198-207.
25 Carotenoid transport is decreased and expression of the lipid transporters SR-BI, NPC1L1, and ABCA1 is downregulated in Caco-2 cells treated with ezetimibe. J Nutr. 2005 Oct;135(10):2305-12. doi: 10.1093/jn/135.10.2305.
26 Compound heterozygosity for two non-synonymous polymorphisms in NPC1L1 in a non-responder to ezetimibe. Clin Genet. 2005 Feb;67(2):175-7. doi: 10.1111/j.1399-0004.2004.00388.x.
27 C-440T/T-331C polymorphisms in the UGT1A9 gene affect the pharmacokinetics of mycophenolic acid in kidney transplantation. Pharmacogenomics. 2007 Sep;8(9):1127-41.
28 Interaction and transport characteristics of mycophenolic acid and its glucuronide via human organic anion transporters hOAT1 and hOAT3. Biochem Pharmacol. 2007 Jun 30;74(1):161-8.
29 Diabetes mellitus reduces activity of human UDP-glucuronosyltransferase 2B7 in liver and kidney leading to decreased formation of mycophenolic acid acyl-glucuronide metabolite. Drug Metab Dispos. 2011 Mar;39(3):448-55.