Details of the Drug Combination

General Information of Drug Combination (ID: DCC8PUG)

Drug Combination Name
Lopinavir Lopinavir
Indication
Disease Entry Status REF
HIV-1 Infection Phase 3 [1]
Component Drugs Lopinavir   DMITQS0 Lopinavir   DMITQS0
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 Lopinavir
Disease Entry ICD 11 Status REF
Human immunodeficiency virus infection 1C62 Approved [2]
Middle East Respiratory Syndrome (MERS) 1D64 Preclinical [3]
Severe acute respiratory syndrome (SARS) 1D65 Preclinical [3]
Lopinavir Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bacterial 23S ribosomal RNA (Bact 23S rRNA) TTLFGBV NOUNIPROTAC Modulator [5]
MERS-CoV 3C-like proteinase (3CLpro) TTWOH4Q R1AB_CVEMC (3248-3553) Inhibitor [3]
SARS-CoV 3C-like protease (3CLpro) TTPZG3C R1AB_CVHSA (3241-3546) Inhibitor [3]
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Lopinavir Interacts with 5 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 1 (ABCC1) DTSYQGK MRP1_HUMAN Substrate [6]
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [7]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [8]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [9]
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Lopinavir Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
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Lopinavir Interacts with 14 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Decreases Activity [11]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Increases Abundance [12]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [13]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Expression [14]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [14]
Prelamin-A/C (LMNA) OT3SG7ZR LMNA_HUMAN Increases Farnesylation [4]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases Expression [14]
Intercellular adhesion molecule 1 (ICAM1) OTTOIX77 ICAM1_HUMAN Increases Expression [15]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Affects Phosphorylation [16]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [15]
C-C motif chemokine 3 (CCL3) OTW2H3ND CCL3_HUMAN Increases Expression [14]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Expression [14]
Leptin (LEP) OT5Q7ODW LEP_HUMAN Decreases Expression [14]
Adiponectin (ADIPOQ) OTNX23LE ADIPO_HUMAN Decreases Expression [14]
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⏷ Show the Full List of 14 DOT(s)
Indication(s) of Lopinavir
Disease Entry ICD 11 Status REF
Human immunodeficiency virus infection 1C62 Approved [2]
Middle East Respiratory Syndrome (MERS) 1D64 Preclinical [3]
Severe acute respiratory syndrome (SARS) 1D65 Preclinical [3]
Lopinavir Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bacterial 23S ribosomal RNA (Bact 23S rRNA) TTLFGBV NOUNIPROTAC Modulator [5]
MERS-CoV 3C-like proteinase (3CLpro) TTWOH4Q R1AB_CVEMC (3248-3553) Inhibitor [3]
SARS-CoV 3C-like protease (3CLpro) TTPZG3C R1AB_CVHSA (3241-3546) Inhibitor [3]
------------------------------------------------------------------------------------
Lopinavir Interacts with 5 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 1 (ABCC1) DTSYQGK MRP1_HUMAN Substrate [6]
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [7]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [8]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [9]
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Lopinavir Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
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Lopinavir Interacts with 14 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Decreases Activity [11]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Increases Abundance [12]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [13]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Expression [14]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [14]
Prelamin-A/C (LMNA) OT3SG7ZR LMNA_HUMAN Increases Farnesylation [4]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases Expression [14]
Intercellular adhesion molecule 1 (ICAM1) OTTOIX77 ICAM1_HUMAN Increases Expression [15]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Affects Phosphorylation [16]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [15]
C-C motif chemokine 3 (CCL3) OTW2H3ND CCL3_HUMAN Increases Expression [14]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Expression [14]
Leptin (LEP) OT5Q7ODW LEP_HUMAN Decreases Expression [14]
Adiponectin (ADIPOQ) OTNX23LE ADIPO_HUMAN Decreases Expression [14]
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⏷ Show the Full List of 14 DOT(s)

References

1 ClinicalTrials.gov (NCT01352715) Study of Options for Second-Line Effective Combination Therapy (SELECT)
2 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
3 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
4 A potent HIV protease inhibitor, darunavir, does not inhibit ZMPSTE24 or lead to an accumulation of farnesyl-prelamin A in cells. J Biol Chem. 2008 Apr 11;283(15):9797-804. doi: 10.1074/jbc.M709629200. Epub 2008 Jan 28.
5 Company report (JMI Laboratories)
6 Inhibition of P-glycoprotein and multidrug resistance-associated proteins modulates the intracellular concentration of lopinavir in cultured CD4 T cells and primary human lymphocytes. J Antimicrob Chemother. 2007 Nov;60(5):987-93.
7 Effects of cytochrome P450 3A (CYP3A) and the drug transporters P-glycoprotein (MDR1/ABCB1) and MRP2 (ABCC2) on the pharmacokinetics of lopinavir. Br J Pharmacol. 2010 Jul;160(5):1224-33.
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 Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
10 Synthesis and antiviral activities of the major metabolites of the HIV protease inhibitor ABT-378 (Lopinavir). Bioorg Med Chem Lett. 2001 Jun 4;11(11):1351-3.
11 Mechanism-based inactivation of CYP3A by HIV protease inhibitors. J Pharmacol Exp Ther. 2005 Feb;312(2):583-91.
12 Functional defect caused by the 4544G>A SNP in ABCC2: potential impact for drug cellular disposition. Pharmacogenet Genomics. 2011 Dec;21(12):884-93. doi: 10.1097/FPC.0b013e32834d672b.
13 Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
14 Some HIV antiretrovirals increase oxidative stress and alter chemokine, cytokine or adiponectin production in human adipocytes and macrophages. Antivir Ther. 2007;12(4):489-500.
15 Heme oxygenase-1-derived bilirubin counteracts HIV protease inhibitor-mediated endothelial cell dysfunction. Free Radic Biol Med. 2016 May;94:218-29. doi: 10.1016/j.freeradbiomed.2016.03.003. Epub 2016 Mar 8.
16 Lopinavir inhibits meningioma cell proliferation by Akt independent mechanism. J Neurooncol. 2011 Feb;101(3):441-8. doi: 10.1007/s11060-010-0281-y. Epub 2010 Jul 2.