General Information of Drug Combination (ID: DC6T1FG)

Drug Combination Name
Sitagliptin Enalapril
Indication
Disease Entry Status REF
Metabolic Syndrome Phase 1 [1]
Component Drugs Sitagliptin   DMGDKXN Enalapril   DMNFUZR
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 Sitagliptin
Disease Entry ICD 11 Status REF
Cystic fibrosis CA25 Approved [2]
Non-insulin dependent diabetes 5A11 Approved [2]
Renal hypoplasia N.A. Approved [2]
Type-2 diabetes 5A11 Approved [3]
Peripheral arterial disease BD4Z Phase 1/2 [4]
Sitagliptin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Dipeptidyl peptidase 4 (DPP-4) TTDIGC1 DPP4_HUMAN Inhibitor [7]
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Sitagliptin Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [9]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [10]
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Sitagliptin Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [11]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [11]
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Indication(s) of Enalapril
Disease Entry ICD 11 Status REF
Congestive heart failure BD10 Approved [5]
Hypertension BA00-BA04 Approved [6]
Malignant essential hypertension BA00 Approved [5]
Enalapril Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Angiotensin-converting enzyme (ACE) TTL69WB ACE_HUMAN Inhibitor [12]
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Enalapril 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 [13]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [14]
Peptide transporter 1 (SLC15A1) DT9G7XN S15A1_HUMAN Substrate [15]
Peptide transporter 2 (SLC15A2) DT8QKNP S15A2_HUMAN Substrate [16]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [17]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [13]
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⏷ Show the Full List of 6 DTP(s)
Enalapril Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [18]
Carboxylesterase 1 (CES1) DEB30C5 EST1_HUMAN Metabolism [19]
Dipeptidase (pepV) DEQMBHW Q84BU9_LACLH Metabolism [20]
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Enalapril Interacts with 13 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases ADR [21]
Solute carrier organic anion transporter family member 1B1 (SLCO1B1) OTNEN8QK SO1B1_HUMAN Affects Abundance [22]
Carbonic anhydrase 2 (CA2) OTJRMUAG CAH2_HUMAN Decreases Activity [23]
Renin (REN) OT52GZR2 RENI_HUMAN Decreases Activity [24]
Angiotensinogen (AGT) OTBZLYR3 ANGT_HUMAN Decreases Expression [25]
Natriuretic peptides A (NPPA) OTMQNTNX ANF_HUMAN Decreases Expression [26]
Erythropoietin (EPO) OTZ90CN4 EPO_HUMAN Decreases Expression [25]
Angiogenin (ANG) OT3ECS6P ANGI_HUMAN Decreases Expression [27]
Tissue factor (F3) OT3MSU3B TF_HUMAN Decreases Expression [28]
Somatotropin (GH1) OT92RTRD SOMA_HUMAN Increases Response To Substance [29]
ATP-binding cassette sub-family C member 4 (ABCC4) OTO27PAL MRP4_HUMAN Increases Transport [30]
B2 bradykinin receptor (BDKRB2) OTOA9D3W BKRB2_HUMAN Increases ADR [21]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Affects Response To Substance [31]
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⏷ Show the Full List of 13 DOT(s)

References

1 ClinicalTrials.gov (NCT00666848) Effect of Sitagliptin and an ACE Inhibitor on Blood Pressure in Metabolic Syndrome
2 Sitagliptin 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: 6286).
4 ClinicalTrials.gov (NCT01619332) Clinical Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LEZ763. U.S. National Institutes of Health.
5 Enalapril FDA Label
6 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: 6322).
7 Novel therapeutics for type 2 diabetes: incretin hormone mimetics (glucagon-like peptide-1 receptor agonists) and dipeptidyl peptidase-4 inhibitors. Pharmacol Ther. 2009 Oct;124(1):113-38.
8 Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
9 265 effect of dietary cholesterol on gallbladder bile lithogenicity and gene expression in the enterohepatic axis of non-obese gallstone and control women. Journal of Hepatology, 2009, 50(09):S105-S106.
10 Transport of the dipeptidyl peptidase-4 inhibitor sitagliptin by human organic anion transporter 3, organic anion transporting polypeptide 4C1, and multidrug resistance P-glycoprotein. J Pharmacol Exp Ther. 2007 May;321(2):673-83.
11 Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab. 2010 Aug;12(8):648-58.
12 Determination of bezafibrate, methotrexate, cyclophosphamide, orlistat and enalapril in waste and surface waters using on-line solid-phase extracti... J Environ Monit. 2009 Apr;11(4):830-8.
13 Vectorial transport of enalapril by Oatp1a1/Mrp2 and OATP1B1 and OATP1B3/MRP2 in rat and human livers. J Pharmacol Exp Ther. 2006 Jul;318(1):395-402.
14 The modified dipeptide, enalapril, an angiotensin-converting enzyme inhibitor, is transported by the rat liver organic anion transport protein. Hepatology. 1998 Nov;28(5):1341-6.
15 The intestinal H+/peptide symporter PEPT1: structure-affinity relationships. Eur J Pharm Sci. 2004 Jan;21(1):53-60.
16 Ethanol inhibits functional activity of the human intestinal dipeptide transporter hPepT1 expressed in Xenopus oocytes. Alcohol Clin Exp Res. 2008 May;32(5):777-84.
17 Uptake of enalapril and expression of organic anion transporting polypeptide 1 in zonal, isolated rat hepatocytes. Drug Metab Dispos. 2000 Jul;28(7):801-6.
18 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
19 Absorption and cleavage of enalapril, a carboxyl ester prodrug, in the rat intestine: in vitro, in situ intestinal perfusion and portal vein cannulation models. Biopharm Drug Dispos. 2015 Sep;36(6):385-397.
20 Characterization and kinetic analysis of enzyme-substrate recognition by three recombinant lactococcal PepVs. Arch Biochem Biophys. 2006 Oct 15;454(2):137-45.
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 Effect of organic anion-transporting polypeptide 1B1 (OATP1B1) polymorphism on the single- and multiple-dose pharmacokinetics of enalapril in healthy Chinese adult men. Clin Ther. 2011 May;33(5):655-63. doi: 10.1016/j.clinthera.2011.04.018.
23 Captopril/enalapril inhibit promiscuous esterase activity of carbonic anhydrase at micromolar concentrations: An initro study. Chem Biol Interact. 2017 Mar 1;265:24-35.
24 A nonpeptide, piperidine renin inhibitor provides renal and cardiac protection in double-transgenic mice expressing human renin and angiotensinogen genes. Cardiovasc Drugs Ther. 2008 Dec;22(6):469-78. doi: 10.1007/s10557-008-6131-x. Epub 2008 Aug 5.
25 Worsening of anemia by angiotensin converting enzyme inhibitors and its prevention by antiestrogenic steroid in chronic hemodialysis patients. J Cardiovasc Pharmacol. 1989;13 Suppl 3:S27-30. doi: 10.1097/00005344-198900133-00007.
26 The effect of early converting enzyme inhibition on neurohumoral activation in acute myocardial infarction. Int J Cardiol. 1993 Nov;42(1):37-45. doi: 10.1016/0167-5273(93)90100-u.
27 Effects of enalapril maleate on blood pressure, renin-angiotensin-aldosterone system, and peripheral sympathetic activity in essential hypertension. Clin Ther. 1987;9(4):390-9.
28 Inhibition of the renin-angiotensin system downregulates tissue factor and vascular endothelial growth factor in human breast carcinoma cells. Thromb Res. 2012 Jun;129(6):736-42. doi: 10.1016/j.thromres.2011.11.047. Epub 2011 Dec 19.
29 Growth hormone aggravates renal abnormalities induced by neonatal enalapril treatment. Pediatr Nephrol. 2003 Sep;18(9):878-86. doi: 10.1007/s00467-003-1197-y. Epub 2003 Jul 23.
30 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.
31 Effect of enalapril and losartan on cytokines in patients with stable angina pectoris awaiting coronary artery bypass grafting and their interaction with polymorphisms in the interleukin-6 gene. Am J Cardiol. 2004 Sep 1;94(5):564-9. doi: 10.1016/j.amjcard.2004.05.017.