Lopinavir
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Also known as A-157378.0ABT-378AluviranKoletraLopinavir component of kaletraLopinavir, (s-(2s,4s,5s))-Lopinavir-LopinavirumSID50111692SID124893167SID144205757SID26757998SID170464773LOPINAVIR (ABT-378)
Summary
Lopinavir (CHEMBL729) is an approved small-molecule antiviral drug; indicated across 17 conditions including hiv infectious disease and aids.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- Indications: 17 conditions
- Clinical trials: 188
- Chemistry: 628.8 Da · C37H48N4O5
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL729 |
| Name | Lopinavir |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | no |
| PubChem CID | 92727 |
| ChEBI | CHEBI:31781 |
| Molecular formula | C37H48N4O5 |
| Molecular weight | 628.8 |
| InChIKey | KJHKTHWMRKYKJE-SUGCFTRWSA-N |
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
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
ChEBI definition: A dicarboxylic acid diamide that is amphetamine is substituted on nitrogen by a (2,6-dimethylphenoxy)acetyl group and on the carbon α- to nitrogen by a (1S,3S)-1-hydroxy-3-{[(2S)-3-methyl-2-(2-oxotetrahydropyrimidin-1-yl)butanoyl]amino}-4-phenylbutyl group. An antiretroviral of the protease inhibitor class, it is used against HIV infections as a fixed-dose combination with another protease inhibitor, ritonavir.
Pharmacological roles (ChEBI): antiviral drug, HIV protease inhibitor, anticoronaviral agent.
Also known as: A-157378.0, ABT-378, Aluviran, Koletra, Lopinavir, Lopinavir component of kaletra, Lopinavir, (s-(2s,4s,5s))-, Lopinavir-, Lopinavirum, lopinavir, SID50111692, LOPINAVIR
Patent coverage: 7,718 distinct patent families (28,308 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.
Targets
Targets
Broader ChEMBL bioactivity targets: 18 (assay-derived). Sample: CAAX prenyl protease 1 homolog, Nuclear receptor ROR-gamma, ATP-binding cassette sub-family C member 4, 5-hydroxytryptamine receptor 2B, Sodium channel protein type 5 subunit alpha, Thromboxane A2 receptor, Progesterone receptor, Muscarinic acetylcholine receptor M1, Alpha-1A adrenergic receptor, Mu-type opioid receptor.
Bioactivity
ChEMBL activities: 11 potent at pChembl ≥ 5 of 24 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| CYP3A4 | 6.39 | Ki | 410 | nM | CHEMBL_ACT_6075217 |
| CYP3A4 | 6 | Ki | 1000 | nM | CHEMBL_ACT_12163656 |
| CYP3A4 | 6 | Ki | 1000 | nM | CHEMBL_ACT_6075218 |
| ABCB1 | 5.77 | IC50 | 1700 | nM | CHEMBL_ACT_11000926 |
| ADRA1A | 5.24 | AC50 | 5817 | nM | CHEMBL_ACT_25137982 |
| TBXA2R | 5.2 | AC50 | 6260 | nM | CHEMBL_ACT_25198041 |
| HTR2B | 5.18 | AC50 | 6600 | nM | CHEMBL_ACT_25227595 |
| ABCG2 | 5.12 | IC50 | 7600 | nM | CHEMBL_ACT_24777426 |
| KCNH2 | 5.07 | IC50 | 8511 | nM | CHEMBL_ACT_5219059 |
| P0DTD1 | 5.04 | IC50 | 9120 | nM | CHEMBL_ACT_25045123 |
| PGR | 5.01 | AC50 | 9712 | nM | CHEMBL_ACT_25204481 |
Target pathways
No target-pathway data for this drug (no mapped target genes).
Indications & clinical
Indications
17 indications (2 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).
| Indication | Trial phase | MONDO | EFO |
|---|---|---|---|
| HIV infectious disease | 4 | MONDO:0005109 | EFO:0000764 |
| AIDS | 3 | MONDO:0012268 | EFO:0000765 |
| Orthocoronavirinae infectious disease | 3 | MONDO:0020753 | MONDO:0100116 |
| severe acute respiratory syndrome | 3 | MONDO:0005091 | EFO:0000694 |
| pneumonia | 3 | MONDO:0005249 | EFO:0003106 |
| influenza | 3 | MONDO:0005812 | EFO:0007328 |
| Kaposi’s sarcoma | 2 | MONDO:0005055 | EFO:0000558 |
| hepatitis C virus infection | 1 | MONDO:0005231 | EFO:0003047 |
| acute respiratory distress syndrome | 1 | MONDO:0006502 | EFO:1000637 |
| anus neoplasm | 1 | MONDO:0003046 | EFO:0003835 |
| tuberculosis | 1 | MONDO:0018076 | MONDO:0018076 |
6 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 188.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE4 | 44 |
| PHASE3 | 39 |
| Not specified | 39 |
| PHASE2 | 34 |
| PHASE1 | 20 |
| PHASE2/PHASE3 | 6 |
| PHASE1/PHASE2 | 5 |
| EARLY_PHASE1 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT00055120 | PHASE4 | COMPLETED | When to Start Anti-HIV Drugs in Patients With Opportunistic Infections |
| NCT00122226 | PHASE4 | UNKNOWN | MEDICLAS Study (Metabolic Effects of Different Classes of AntiretroviralS) |
| NCT00143689 | PHASE4 | COMPLETED | NRTI-Sparing Pilot Study |
| NCT00159224 | PHASE4 | COMPLETED | Induction-maintenance of Lopinavir/r in HIV-infected Subjects |
| NCT00234962 | PHASE4 | TERMINATED | Study of Adherence Effects and Clinical Outcomes of Kaletra Based HIV Antiviral Therapy |
| NCT00234975 | PHASE4 | COMPLETED | Safety of Lopinavir/Ritonavir (Kaletra) in HIV/HCV Co-infected Subjects vs Baseline Liver Biopsy Metavir Score |
| NCT00342355 | PHASE4 | COMPLETED | Antiretroviral Therapy for Advanced HIV Disease in South Africa |
| NCT00420355 | PHASE4 | TERMINATED | Pharmacokinetic Study of Two HIV Protease Inhibitors in Patients |
| NCT00438152 | PHASE4 | COMPLETED | Lopinavir Capsules to Kaletra or Invirase Tablets |
| NCT00444379 | PHASE4 | COMPLETED | Anti-Retrovirals for Kaposi’s Sarcoma |
| NCT00476359 | PHASE4 | COMPLETED | A PK and Salvage Study for Children With HIV-infection |
| NCT00564772 | PHASE4 | COMPLETED | Raltegravir Kaletra Pharmacokinetics |
| NCT00605098 | PHASE4 | COMPLETED | Pharmacokinetics of the Tablet Formulation of Lopinavir/r as Standard and Increased Dosage During Pregnancy |
| NCT00632970 | PHASE4 | TERMINATED | Raltegravir vs. Lopinavir/Ritonavir, Both in Combination With Truvada, in HIV+ Treatment Naive Individuals |
| NCT00648999 | PHASE4 | COMPLETED | Safety and Efficacy of Kaletra in ARV Therapy Experienced Patients |
| NCT00661349 | PHASE4 | TERMINATED | Trial About Hepatic Security of Antiretroviral Treatment Based on Kaletra Versus Nevirapine in Co-infected HIV/HCV Patients |
| NCT00752037 | PHASE4 | COMPLETED | Safety Study of Lopinavir/Ritonavir With Raltegravir in HIV-infected Patients |
| NCT00771498 | PHASE4 | COMPLETED | An Evaluation of the Pharmacological Interaction of Lopinavir/r and Rifampin |
| NCT00775606 | PHASE4 | TERMINATED | Immune Reconstitution of Lopinavir/Ritonavir-Based vs Efavirenz-based HAART in Advanced HIV Disease |
| NCT00810108 | PHASE4 | COMPLETED | Lopinavir/Ritonavir (Kaletra) PK in Children |
| NCT00866021 | PHASE4 | COMPLETED | Treatment of HIV/HCV Coinfection With Peg-IFN and Ribavirin in Patients Receiving ART Monotherapy With Lopinavir/r |
| NCT00931463 | PHASE4 | COMPLETED | A Trial of 2 Options for Second Line Combination Antiretroviral Therapy Following Virological Failure of a Standard Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI)+2N(t)RTI First Line Regimen |
| NCT00981318 | PHASE4 | TERMINATED | Pilot Assessment of Lopinavir/Ritonavir and Maraviroc |
| NCT00994344 | PHASE4 | COMPLETED | Clinical Study to Evaluate the Efficacy and Safety of Lopinavir/Ritonavir Monotherapy Versus Darunavir/Ritonavir Monotherapies as Simplification Switching Strategies of PI/NNRTI-Triple Therapy Based-Regimens |
| NCT01057433 | PHASE4 | COMPLETED | Drug-Drug Interaction of Lopinavir/Ritonavir on Pitavastatin |
| NCT01068873 | PHASE4 | TERMINATED | Kaletra and Maraviroc in Antiretroviral Therapy (ART)-Naive Patients (KALMAR Study) |
| NCT01088516 | PHASE4 | COMPLETED | Clinical Study of an Aluvia-based HAART Regimen for Prevention of Mother-to-child HIV Transmission in Africa |
| NCT01166477 | PHASE4 | COMPLETED | Clinical Trial, Open-label, Randomised, in Order to Compare the Quality of Life for Those VIH+ Patients That Start With Monotherapy on LPV/r Tablets Vs. Triple Therapy With a Boosted Protease Inhibitor |
| NCT01189695 | PHASE4 | COMPLETED | Maintenance Boosted Lopinavir Monotherapy Following Salvage Protease-inhibitor (PI) Based Regimen in HIV With Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Based Regimen Failure |
| NCT01192035 | PHASE4 | COMPLETED | PI or NNRTI as First-line Treatment of HIV in West Africa - the PIONA Trial |
| NCT01445223 | PHASE4 | COMPLETED | A Study on Antiretroviral Therapy (ART) Naïve Patients On Different Regimens to Treat Hiv (NORTHIV) |
| NCT01513122 | PHASE4 | COMPLETED | Bone and Body Comp: A Sub Study of the SECOND-LINE Study |
| NCT01637558 | PHASE4 | COMPLETED | Optimal Dosing of 1st Line Antituberculosis and Antiretroviral Drugs in Children (a Pharmacokinetic Study) |
| NCT01700790 | PHASE4 | TERMINATED | Pharmacokinetic Study of Super-boosted Lopinavir/Ritonavir Given With Rifampin |
| NCT01772940 | PHASE4 | COMPLETED | Nevirapine vs Ritonavir-boosted Lopinavir in ART Naive HIV-infected Adults in a Resource Limited Setting |
| NCT02348177 | PHASE4 | COMPLETED | Pharmacokinetics of Lopinavir/Ritonavir Superboosting in Infants and Young Children Co-infected With HIV and TB |
| NCT02712801 | PHASE4 | COMPLETED | Antiretroviral Regime for Viral Eradication in Newborns |
| NCT04252885 | PHASE4 | COMPLETED | The Efficacy of Lopinavir Plus Ritonavir and Arbidol Against Novel Coronavirus Infection |
| NCT04255017 | PHASE4 | UNKNOWN | A Prospective/Retrospective,Randomized Controlled Clinical Study of Antiviral Therapy in the 2019-nCoV Pneumonia |
| NCT04286503 | PHASE4 | UNKNOWN | The Clinical Study of Carrimycin on Treatment Patients With COVID-19 |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No CPIC/DPWG dosing guideline, but PharmGKB curates 8 clinical and 48 variant annotation(s) for this drug (gene-keyed; see PharmGKB).
Related molecules
Related molecules
No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).