General Information of Drug (ID: DMITQS0)

Drug Name
Lopinavir
Synonyms
AIDS032937; Aluvia (TN); Aluviran; Kaletra (TN); Koletra; LPV; Lopinavir (JAN/USAN/INN); Lopinavir [USAN:INN:BAN]; RS-346; A 157378; A 157378.0; A-157378-0; A-157378.0; ABT 157378; ABT 378; ABT-378; ABT-378
Indication
Disease Entry ICD 11 Status REF
Human immunodeficiency virus infection 1C62 Approved [1]
Middle East Respiratory Syndrome (MERS) 1D64 Preclinical [2]
Severe acute respiratory syndrome (SARS) 1D65 Preclinical [2]
Therapeutic Class
Anti-HIV Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 3 Molecular Weight (mw) 628.8
Logarithm of the Partition Coefficient (xlogp) 5.9
Rotatable Bond Count (rotbonds) 15
Hydrogen Bond Donor Count (hbonddonor) 4
Hydrogen Bond Acceptor Count (hbondacc) 5
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
Elimination
2.2% of drug is excreted from urine in the unchanged form [3]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 24.21774 micromolar/kg/day [4]
Chemical Identifiers
Formula
C37H48N4O5
IUPAC Name
(2S)-N-[(2S,4S,5S)-5-[[2-(2,6-dimethylphenoxy)acetyl]amino]-4-hydroxy-1,6-diphenylhexan-2-yl]-3-methyl-2-(2-oxo-1,3-diazinan-1-yl)butanamide
Canonical SMILES
CC1=C(C(=CC=C1)C)OCC(=O)N[C@@H](CC2=CC=CC=C2)[C@H](C[C@H](CC3=CC=CC=C3)NC(=O)[C@H](C(C)C)N4CCCNC4=O)O
InChI
InChI=1S/C37H48N4O5/c1-25(2)34(41-20-12-19-38-37(41)45)36(44)39-30(21-28-15-7-5-8-16-28)23-32(42)31(22-29-17-9-6-10-18-29)40-33(43)24-46-35-26(3)13-11-14-27(35)4/h5-11,13-18,25,30-32,34,42H,12,19-24H2,1-4H3,(H,38,45)(H,39,44)(H,40,43)/t30-,31-,32-,34-/m0/s1
InChIKey
KJHKTHWMRKYKJE-SUGCFTRWSA-N
Cross-matching ID
PubChem CID
92727
ChEBI ID
CHEBI:31781
CAS Number
192725-17-0
DrugBank ID
DB01601
TTD ID
D0U5GB
VARIDT ID
DR00290
INTEDE ID
DR0976
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Bacterial 23S ribosomal RNA (Bact 23S rRNA) TTLFGBV NOUNIPROTAC Modulator [5]
MERS-CoV 3C-like proteinase (3CLpro) TTWOH4Q R1AB_CVEMC (3248-3553) Inhibitor [2]
SARS-CoV 3C-like protease (3CLpro) TTPZG3C R1AB_CVHSA (3241-3546) Inhibitor [2]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [6]
Multidrug resistance-associated protein 1 (ABCC1) DTSYQGK MRP1_HUMAN Substrate [7]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [8]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [9]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME
DE4LYSA CP3A4_HUMAN Substrate [10]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Adiponectin (ADIPOQ) OTNX23LE ADIPO_HUMAN Gene/Protein Processing [11]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Regulation of Drug Effects [12]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Gene/Protein Processing [13]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Gene/Protein Processing [11]
C-C motif chemokine 3 (CCL3) OTW2H3ND CCL3_HUMAN Gene/Protein Processing [11]
CAAX prenyl protease 1 homolog OTUMYTEV FACE1_HUMAN Gene/Protein Processing [14]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Gene/Protein Processing [15]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Gene/Protein Processing [16]
Intercellular adhesion molecule 1 (ICAM1) OTTOIX77 ICAM1_HUMAN Gene/Protein Processing [16]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Gene/Protein Processing [11]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Lopinavir
DDI Drug Name DDI Drug ID Severity Mechanism Disease REF
Rilpivirine DMJ0QOW Moderate Increased risk of prolong QT interval by the combination of Lopinavir and Rilpivirine. Human immunodeficiency virus disease [1C60-1C62] [17]
Coadministration of a Drug Treating the Disease Different from Lopinavir (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Bedaquiline DM3906J Major Increased risk of prolong QT interval by the combination of Lopinavir and Bedaquiline. Antimicrobial drug resistance [MG50-MG52] [18]
Levalbuterol DM5YBO1 Moderate Increased risk of prolong QT interval by the combination of Lopinavir and Levalbuterol. Asthma [CA23] [19]
Retigabine DMGNYIH Moderate Increased risk of prolong QT interval by the combination of Lopinavir and Retigabine. Behcet disease [4A62] [17]
Eribulin DM1DX4Q Moderate Increased risk of prolong QT interval by the combination of Lopinavir and Eribulin. Breast cancer [2C60-2C6Y] [17]
Olodaterol DM62B78 Moderate Increased risk of prolong QT interval by the combination of Lopinavir and Olodaterol. Chronic obstructive pulmonary disease [CA22] [19]
Indacaterol DMQJHR7 Moderate Increased risk of ventricular arrhythmias by the combination of Lopinavir and Indacaterol. Chronic obstructive pulmonary disease [CA22] [19]
Pasireotide DMHM7JS Major Increased risk of prolong QT interval by the combination of Lopinavir and Pasireotide. Cushing syndrome [5A70] [20]
Tetrabenazine DMYWQ0O Moderate Increased risk of prolong QT interval by the combination of Lopinavir and Tetrabenazine. Dissociative neurological symptom disorder [6B60] [17]
Deutetrabenazine DMUPFLI Moderate Increased risk of prolong QT interval by the combination of Lopinavir and Deutetrabenazine. Dystonic disorder [8A02] [17]
Polyethylene glycol DM4I1JP Moderate Increased risk of ventricular arrhythmias by the combination of Lopinavir and Polyethylene glycol. Irritable bowel syndrome [DD91] [21]
Phenolphthalein DM5SICT Moderate Increased risk of ventricular arrhythmias by the combination of Lopinavir and Phenolphthalein. Irritable bowel syndrome [DD91] [20]
Hydroxychloroquine DMSIVND Major Increased risk of prolong QT interval by the combination of Lopinavir and Hydroxychloroquine. Malaria [1F40-1F45] [22]
Inotuzumab ozogamicin DMAC130 Moderate Increased risk of prolong QT interval by the combination of Lopinavir and Inotuzumab ozogamicin. Malignant haematopoietic neoplasm [2B33] [17]
Vemurafenib DM62UG5 Major Increased risk of prolong QT interval by the combination of Lopinavir and Vemurafenib. Melanoma [2C30] [17]
Fingolimod DM5JVAN Major Increased risk of ventricular arrhythmias by the combination of Lopinavir and Fingolimod. Multiple sclerosis [8A40] [17]
Lofexidine DM1WXA6 Moderate Increased risk of prolong QT interval by the combination of Lopinavir and Lofexidine. Opioid use disorder [6C43] [17]
Triclabendazole DMPWGBR Moderate Increased risk of prolong QT interval by the combination of Lopinavir and Triclabendazole. Parasitic worm infestation [1F90] [17]
Macimorelin DMQYJIR Major Increased risk of prolong QT interval by the combination of Lopinavir and Macimorelin. Pituitary gland disorder [5A60-5A61] [23]
Degarelix DM3O8QY Moderate Increased risk of prolong QT interval by the combination of Lopinavir and Degarelix. Prostate cancer [2C82] [21]
ABIRATERONE DM8V75C Moderate Increased risk of prolong QT interval by the combination of Lopinavir and ABIRATERONE. Prostate cancer [2C82] [21]
Selexipag DMAHSU0 Minor Decreased metabolism of Lopinavir caused by Selexipag mediated inhibition of CYP450 enzyme. Pulmonary hypertension [BB01] [24]
Amisulpride DMSJVAM Major Increased risk of prolong QT interval by the combination of Lopinavir and Amisulpride. Schizophrenia [6A20] [25]
Asenapine DMSQZE2 Moderate Increased risk of prolong QT interval by the combination of Lopinavir and Asenapine. Schizophrenia [6A20] [17]
Armodafinil DMGB035 Moderate Increased metabolism of Lopinavir caused by Armodafinil mediated induction of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [26]
Vandetanib DMRICNP Major Increased risk of prolong QT interval by the combination of Lopinavir and Vandetanib. Solid tumour/cancer [2A00-2F9Z] [20]
Triptorelin DMTK4LS Moderate Increased risk of prolong QT interval by the combination of Lopinavir and Triptorelin. Solid tumour/cancer [2A00-2F9Z] [21]
Pitolisant DM8RFNJ Moderate Increased risk of prolong QT interval by the combination of Lopinavir and Pitolisant. Somnolence [MG42] [17]
Telavancin DM58VQX Moderate Increased risk of prolong QT interval by the combination of Lopinavir and Telavancin. Staphylococcal/streptococcal disease [1B5Y] [17]
Lenvatinib DMB1IU4 Moderate Increased risk of prolong QT interval by the combination of Lopinavir and Lenvatinib. Thyroid cancer [2D10] [17]
⏷ Show the Full List of 29 DDI Information of This Drug

References

1 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
2 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
3 BDDCS applied to over 900 drugs
4 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
5 Company report (JMI Laboratories)
6 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.
7 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.
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 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.
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 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.
15 Mechanism-based inactivation of CYP3A by HIV protease inhibitors. J Pharmacol Exp Ther. 2005 Feb;312(2):583-91.
16 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.
17 Canadian Pharmacists Association.
18 Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
19 Product Information. Arcapta Neohaler (indacaterol). Novartis Pharmaceuticals, East Hanover, NJ.
20 Cerner Multum, Inc. "Australian Product Information.".
21 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
22 Product Information. Hydroxychloroquine Sulfate (hydroxychloroquine). Prasco Laboratories, Cincinnati, OH.
23 Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
24 Kaufmann P, Niglis S, Bruderer S, et al. "Effect of lopinavir/ritonavir on the pharmacokinetics of selexipag an oral prostacyclin receptor agonist and its active metabolite in healthy subjects." Br J Clin Pharmacol (2015):. [PMID: 25851691]
25 Product Information. Barhemsys (amisulpride). Acacia Pharma, Inc, Indianapolis, IN.
26 Product Information. Nuvigil (armodafinil). Cephalon Inc, West Chester, PA.