Details of the Drug Combination

General Information of Drug Combination (ID: DCULCLN)

Drug Combination Name
Lisinopril Carvedilol
Indication
Disease Entry Status REF
Breast Carcinoma Phase 2 [1]
Component Drugs Lisinopril   DMUOK4C Carvedilol   DMHTEAO
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 Lisinopril
Disease Entry ICD 11 Status REF
Chronic heart failure BD1Z Approved [2]
Hypertension BA00-BA04 Approved [3]
Myocardial infarction BA41-BA43 Approved [2]
Coronavirus Disease 2019 (COVID-19) 1D6Y Investigative [4]
High blood pressure BA00 Investigative [2]
Lisinopril Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Angiotensin-converting enzyme (ACE) TTL69WB ACE_HUMAN Inhibitor [8]
HUMAN angiotensin-converting enzyme (ACE) TTGFNPD ACE_HUMAN Inhibitor [4]
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Lisinopril Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Peptide transporter 1 (SLC15A1) DT9G7XN S15A1_HUMAN Substrate [9]
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Lisinopril Interacts with 9 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Angiotensin-converting enzyme (ACE) OTDF1964 ACE_HUMAN Decreases Activity [10]
Renin (REN) OT52GZR2 RENI_HUMAN Increases Expression [11]
Angiotensinogen (AGT) OTBZLYR3 ANGT_HUMAN Decreases Expression [12]
Natriuretic peptides A (NPPA) OTMQNTNX ANF_HUMAN Decreases Expression [12]
Endothelin-1 (EDN1) OTZCACEG EDN1_HUMAN Decreases Secretion [13]
Insulin-like growth factor-binding protein 1 (IGFBP1) OT6UQV2K IBP1_HUMAN Increases Expression [14]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [15]
HLA class I histocompatibility antigen, alpha chain G (HLA-G) OTMLK1KN HLAG_HUMAN Affects Expression [16]
B2 bradykinin receptor (BDKRB2) OTOA9D3W BKRB2_HUMAN Increases ADR [17]
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⏷ Show the Full List of 9 DOT(s)
Indication(s) of Carvedilol
Disease Entry ICD 11 Status REF
Chronic heart failure BD1Z Approved [5]
Congestive heart failure BD10 Approved [6]
Pulmonary hypertension BB01 Approved [5]
Coronavirus Disease 2019 (COVID-19) 1D6Y Investigative [7]
Carvedilol Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
HUAMN alpha-1 adrenergic receptor (ADRA1) TTDBOI7 ADA1A_HUMAN; ADA1B_HUMAN; ADA1D_HUMAN Inhibitor [19]
Adrenergic receptor Alpha-1 (ADRA1) TTG28O6 NOUNIPROTAC Antagonist [20]
HUMAN beta adrenergic receptor (BAR) TTJB8UY ADRB1_HUMAN; ADRB2_HUMAN; ADRB3_HUMAN Antagonist [7]
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Carvedilol Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [21]
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Carvedilol Interacts with 7 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [22]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [23]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [24]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [25]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [26]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [27]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DEB3CV1 UD2B7_HUMAN Metabolism [24]
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⏷ Show the Full List of 7 DME(s)
Carvedilol Interacts with 28 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Affects Glucuronidation [28]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Transport [29]
Beta-1 adrenergic receptor (ADRB1) OTQBWN4U ADRB1_HUMAN Increases Activity [30]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [31]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Increases Phosphorylation [32]
Potassium channel subfamily K member 3 (KCNK3) OTWMAV6G KCNK3_HUMAN Decreases Activity [33]
Renin (REN) OT52GZR2 RENI_HUMAN Decreases Expression [34]
Angiotensinogen (AGT) OTBZLYR3 ANGT_HUMAN Decreases Expression [35]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Decreases Expression [36]
Natriuretic peptides A (NPPA) OTMQNTNX ANF_HUMAN Decreases Expression [37]
Vasopressin-neurophysin 2-copeptin (AVP) OTAVZ76K NEU2_HUMAN Decreases Expression [38]
Insulin (INS) OTZ85PDU INS_HUMAN Decreases Expression [39]
C-reactive protein (CRP) OT0RFT8F CRP_HUMAN Decreases Expression [40]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Activity [41]
Endothelin-1 (EDN1) OTZCACEG EDN1_HUMAN Decreases Expression [42]
Beta-2 adrenergic receptor (ADRB2) OTSDOX4Q ADRB2_HUMAN Increases Phosphorylation [31]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [36]
Matrix metalloproteinase-9 (MMP9) OTB2QDAV MMP9_HUMAN Affects Activity [43]
Natriuretic peptides B (NPPB) OTSN2IPY ANFB_HUMAN Decreases Expression [44]
Gap junction alpha-1 protein (GJA1) OTT94MKL CXA1_HUMAN Increases Expression [45]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Increases Expression [46]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [31]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [47]
Adiponectin (ADIPOQ) OTNX23LE ADIPO_HUMAN Decreases Expression [44]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [41]
Ryanodine receptor 2 (RYR2) OT0PF19E RYR2_HUMAN Increases Activity [48]
Vascular endothelial growth factor receptor 2 (KDR) OT15797V VGFR2_HUMAN Increases ADR [17]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Increases ADR [17]
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⏷ Show the Full List of 28 DOT(s)

References

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2 Lisinopril FDA Label
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5 Carvedilol FDA Label
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31 A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling. Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16657-62. doi: 10.1073/pnas.0707936104. Epub 2007 Oct 9.
32 Beta-blockers alprenolol and carvedilol stimulate beta-arrestin-mediated EGFR transactivation. Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14555-60.
33 Carvedilol targets human K2P 3.1 (TASK1) K+ leak channels. Br J Pharmacol. 2011 Jul;163(5):1099-110. doi: 10.1111/j.1476-5381.2011.01319.x.
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38 Lower plasma noradrenaline and blood viscosity on carvedilol vs atenolol in men with recent myocardial infarction. Blood Press. 2002;11(6):377-84. doi: 10.1080/080370502321095357.
39 After myocardial infarction carvedilol improves insulin resistance compared to metoprolol. Clin Res Cardiol. 2006 Feb;95(2):99-104. doi: 10.1007/s00392-006-0336-4. Epub 2006 Feb 6.
40 Effects of carvedilol on oxidative stress in polymorphonuclear and mononuclear cells in patients with essential hypertension. Am J Med. 2004 Apr 1;116(7):460-5. doi: 10.1016/j.amjmed.2003.10.029.
41 Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
42 Carvedilol inhibits endothelin-1 biosynthesis in cultured human coronary artery endothelial cells. J Mol Cell Cardiol. 1998 Jan;30(1):167-73. doi: 10.1006/jmcc.1997.0582.
43 Adrenoceptor blockade alters plasma gelatinase activity in patients with heart failure and MMP-9 promoter activity in a human cell line (ECV304). Pharmacol Res. 2006 Jul;54(1):57-64. doi: 10.1016/j.phrs.2006.02.006. Epub 2006 Feb 28.
44 Effect of carvedilol on plasma adiponectin concentration in patients with chronic heart failure. Circ J. 2009 Jun;73(6):1067-73. doi: 10.1253/circj.cj-08-1026. Epub 2009 Apr 14.
45 Reduced expression of endothelial connexins 43 and 37 in hypertensive rats is rectified after 7-day carvedilol treatment. Am J Hypertens. 2006 Feb;19(2):129-35. doi: 10.1016/j.amjhyper.2005.08.020.
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47 Antiarrhythmic drug carvedilol inhibits HERG potassium channels. Cardiovasc Res. 2001 Feb 1;49(2):361-70. doi: 10.1016/s0008-6363(00)00265-0.
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