Details of the Drug

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

Affected Organisms

Human Immunodeficiency VirusSARS-CoV-2

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)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

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: CHEMBL729
CAS Number: 192725-17-0
UNII: 2494G1JF75
DrugBank ID: DB01601
TTD ID: D0U5GB
VARIDT ID: DR00290
INTEDE ID: DR0976

Drug-Molecule Activity Atlas (DMA)^NEW

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Drug Pharmacogenomic Perturbation (DPP)^NEW

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Drug ADMET Endpoint Profile (DAE)^NEW

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Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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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
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Gene/Protein Processing	[11]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Gene/Protein Processing	[12]
C-C motif chemokine 3 (CCL3)	OTW2H3ND	CCL3_HUMAN	Gene/Protein Processing	[12]
CAAX prenyl protease 1 homolog	OTUMYTEV	FACE1_HUMAN	Gene/Protein Processing	[13]
Prelamin-A/C (LMNA)	OT3SG7ZR	LMNA_HUMAN	Post-Translational Modifications	[13]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Post-Translational Modifications	[14]

Molecular Interaction Atlas (MIA)

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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]	[15]

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]	[16]
Levalbuterol	DM5YBO1	Moderate	Increased risk of prolong QT interval by the combination of Lopinavir and Levalbuterol.	Asthma [CA23]	[17]
Retigabine	DMGNYIH	Moderate	Increased risk of prolong QT interval by the combination of Lopinavir and Retigabine.	Behcet disease [4A62]	[15]
Eribulin	DM1DX4Q	Moderate	Increased risk of prolong QT interval by the combination of Lopinavir and Eribulin.	Breast cancer [2C60-2C6Y]	[15]
Olodaterol	DM62B78	Moderate	Increased risk of prolong QT interval by the combination of Lopinavir and Olodaterol.	Chronic obstructive pulmonary disease [CA22]	[17]
Indacaterol	DMQJHR7	Moderate	Increased risk of ventricular arrhythmias by the combination of Lopinavir and Indacaterol.	Chronic obstructive pulmonary disease [CA22]	[17]
Pasireotide	DMHM7JS	Major	Increased risk of prolong QT interval by the combination of Lopinavir and Pasireotide.	Cushing syndrome [5A70]	[18]
Tetrabenazine	DMYWQ0O	Moderate	Increased risk of prolong QT interval by the combination of Lopinavir and Tetrabenazine.	Dissociative neurological symptom disorder [6B60]	[15]
Deutetrabenazine	DMUPFLI	Moderate	Increased risk of prolong QT interval by the combination of Lopinavir and Deutetrabenazine.	Dystonic disorder [8A02]	[15]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of ventricular arrhythmias by the combination of Lopinavir and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[19]
Phenolphthalein	DM5SICT	Moderate	Increased risk of ventricular arrhythmias by the combination of Lopinavir and Phenolphthalein.	Irritable bowel syndrome [DD91]	[18]
Hydroxychloroquine	DMSIVND	Major	Increased risk of prolong QT interval by the combination of Lopinavir and Hydroxychloroquine.	Malaria [1F40-1F45]	[20]
Inotuzumab ozogamicin	DMAC130	Moderate	Increased risk of prolong QT interval by the combination of Lopinavir and Inotuzumab ozogamicin.	Malignant haematopoietic neoplasm [2B33]	[15]
Vemurafenib	DM62UG5	Major	Increased risk of prolong QT interval by the combination of Lopinavir and Vemurafenib.	Melanoma [2C30]	[15]
Fingolimod	DM5JVAN	Major	Increased risk of ventricular arrhythmias by the combination of Lopinavir and Fingolimod.	Multiple sclerosis [8A40]	[15]
Lofexidine	DM1WXA6	Moderate	Increased risk of prolong QT interval by the combination of Lopinavir and Lofexidine.	Opioid use disorder [6C43]	[15]
Triclabendazole	DMPWGBR	Moderate	Increased risk of prolong QT interval by the combination of Lopinavir and Triclabendazole.	Parasitic worm infestation [1F90]	[15]
Macimorelin	DMQYJIR	Major	Increased risk of prolong QT interval by the combination of Lopinavir and Macimorelin.	Pituitary gland disorder [5A60-5A61]	[21]
Degarelix	DM3O8QY	Moderate	Increased risk of prolong QT interval by the combination of Lopinavir and Degarelix.	Prostate cancer [2C82]	[19]
ABIRATERONE	DM8V75C	Moderate	Increased risk of prolong QT interval by the combination of Lopinavir and ABIRATERONE.	Prostate cancer [2C82]	[19]
Selexipag	DMAHSU0	Minor	Decreased metabolism of Lopinavir caused by Selexipag mediated inhibition of CYP450 enzyme.	Pulmonary hypertension [BB01]	[22]
Amisulpride	DMSJVAM	Major	Increased risk of prolong QT interval by the combination of Lopinavir and Amisulpride.	Schizophrenia [6A20]	[23]
Asenapine	DMSQZE2	Moderate	Increased risk of prolong QT interval by the combination of Lopinavir and Asenapine.	Schizophrenia [6A20]	[15]
Armodafinil	DMGB035	Moderate	Increased metabolism of Lopinavir caused by Armodafinil mediated induction of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[24]
Vandetanib	DMRICNP	Major	Increased risk of prolong QT interval by the combination of Lopinavir and Vandetanib.	Solid tumour/cancer [2A00-2F9Z]	[18]
Triptorelin	DMTK4LS	Moderate	Increased risk of prolong QT interval by the combination of Lopinavir and Triptorelin.	Solid tumour/cancer [2A00-2F9Z]	[19]
Pitolisant	DM8RFNJ	Moderate	Increased risk of prolong QT interval by the combination of Lopinavir and Pitolisant.	Somnolence [MG42]	[15]
Telavancin	DM58VQX	Moderate	Increased risk of prolong QT interval by the combination of Lopinavir and Telavancin.	Staphylococcal/streptococcal disease [1B5Y]	[15]
Lenvatinib	DMB1IU4	Moderate	Increased risk of prolong QT interval by the combination of Lopinavir and Lenvatinib.	Thyroid cancer [2D10]	[15]


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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	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.
12	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.
13	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.
14	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.
15	Canadian Pharmacists Association.
16	Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
17	Product Information. Arcapta Neohaler (indacaterol). Novartis Pharmaceuticals, East Hanover, NJ.
18	Cerner Multum, Inc. "Australian Product Information.".
19	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
20	Product Information. Hydroxychloroquine Sulfate (hydroxychloroquine). Prasco Laboratories, Cincinnati, OH.
21	Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
22	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]
23	Product Information. Barhemsys (amisulpride). Acacia Pharma, Inc, Indianapolis, IN.
24	Product Information. Nuvigil (armodafinil). Cephalon Inc, West Chester, PA.