Details of the Drug Combination

General Information of Drug Combination (ID: DCSUC3R)

Drug Combination Name
Bempedoic acid Ezetimibe
Indication
Disease Entry Status REF
Hypercholesterolemia Phase 3 [1]
Component Drugs Bempedoic acid   DM1CI9R Ezetimibe   DM7A8TW
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Bempedoic acid
Disease Entry ICD 11 Status REF
Familial hypercholesterolemia 5C80.00 Approved [2]
Cardiovascular disease BA00-BE2Z Phase 3 [3]
Bempedoic acid Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Cholesterol synthesis (Chole synth) TTRA79S NOUNIPROTAC Inhibitor [2]
ATP-citrate synthase (ACLY) TT0Z6Y2 ACLY_HUMAN Inhibitor [2]
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Indication(s) of Ezetimibe
Disease Entry ICD 11 Status REF
Atherosclerosis BD40 Approved [4]
Hypercholesterolaemia 5C80.0 Approved [5]
Hyperlipidemia 5C80.Z Approved [4]
Hyperlipidemia, familial combined, LPL related N.A. Approved [4]
Non-alcoholic fatty liver disease DB92 Approved [4]
Type-1/2 diabetes 5A10-5A11 Approved [4]
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 [7]
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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 [8]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [9]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [10]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [11]
Multidrug resistance-associated protein 3 (ABCC3) DTQ3ZHF MRP3_HUMAN Substrate [10]
Bile salt export pump (ABCB11) DTJ0EW4 ABCBB_HUMAN Substrate [12]
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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 [13]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [13]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DEB3CV1 UD2B7_HUMAN Metabolism [13]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DEF2WXN UD13_HUMAN Metabolism [14]
UDP-glucuronosyltransferase 2B15 (UGT2B15) DENZ6B1 UDB15_HUMAN Metabolism [13]
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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 [12]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) OTRT3F3U HMDH_HUMAN Increases Activity [15]
Phospholipid-transporting ATPase ABCA1 (ABCA1) OT94G6BQ ABCA1_HUMAN Decreases Expression [16]
Retinoic acid receptor gamma (RARG) OT8LHMDH RARG_HUMAN Decreases Expression [16]
Sterol regulatory element-binding protein 1 (SREBF1) OTWBRPAI SRBP1_HUMAN Decreases Expression [16]
Oxysterols receptor LXR-beta (NR1H2) OT4APA60 NR1H2_HUMAN Decreases Expression [16]
Sterol regulatory element-binding protein 2 (SREBF2) OTBXUNPL SRBP2_HUMAN Decreases Expression [16]
Scavenger receptor class B member 1 (SCARB1) OTAE1UA1 SCRB1_HUMAN Decreases Expression [16]
NPC1-like intracellular cholesterol transporter 1 (NPC1L1) OT6GWW1P NPCL1_HUMAN Decreases Response To Substance [17]
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⏷ Show the Full List of 9 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Hypercholesterolemia DCTW8J5 N. A. Phase 2 [18]
High blood cholesterol level DC6TXZT N. A. Phase 1 [3]
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References

1 ClinicalTrials.gov (NCT03001076) Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) as Add-on to Ezetimibe Therapy in Patients With Elevated LDL-C (CLEAR Tranquility)
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 Ezetimibe FDA Label
5 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).
6 Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of ezetimibe (Zetia). Drug Metab Dispos. 2004 Mar;32(3):314-20.
7 Update on patented cholesterol absorption inhibitors. Expert Opin Ther Pat. 2009 Aug;19(8):1083-107.
8 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.
9 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.
10 Complex pharmacokinetic behavior of ezetimibe depends on abcc2, abcc3, and abcg2. Drug Metab Dispos. 2009 Aug;37(8):1698-702.
11 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.
12 Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
13 Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-94.
14 Drug interactions between the immunosuppressant tacrolimus and the cholesterol absorption inhibitor ezetimibe in healthy volunteers. Clin Pharmacol Ther. 2011 Apr;89(4):524-8.
15 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.
16 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.
17 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.
18 ClinicalTrials.gov (NCT03051100) Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180mg, Ezetimibe 10mg, and Atorvastatin 20 mg Triplet Therapy in Patients With Elevated LDL-C