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Fig. 1 · Structure
Cat. No.
A10537
CAS No.
192725-17-0
Formula
C37H48N4O5
Mol. Weight
628.8

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Lopinavir (ABT-378)

Cat. No. A10537 CAS 192725-17-0

HIV Protease inhibitor

Lopinavir is an inhibitor of the HIV protease.

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Biological Activity

Target & Activity

Target Activity Value
HIV protease (Cell-free assay) Ki 1.3 pM

Cellular Effect

Cell Line Activity Value Description Reference
Caco-2 IC50 19.11 μM Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells after 48 hours by high content imaging 10.21203/rs.3.rs-23951/v1
Caco-2 CC50 2128.78 μM Toxicity against Caco-2 cells determined at 48 hours by intracellular ATP concentration using the CellTiter-Glo Luminescent Cell Viability Assay 10.21203/rs.3.rs-23951/v1
CCRF-CEM EC50 260 nM Antiviral activity against HIV2 ROD with protease G17N/V47A mutation infected in human CEM cells assessed as inhibition of virus production after 7 days by Lenti-RT activity assay [PMID: 17576848]
CCRF-CEM EC50 28 nM Antiviral activity against HIV2 ROD with protease G17N mutation infected in human CEM cells assessed as inhibition of virus production after 7 days by Lenti-RT activity assay [PMID: 17576848]
CCRF-CEM EC50 340 nM Antiviral activity against HIV2 ROD with protease V47A mutation infected in human CEM cells assessed as inhibition of virus production after 7 days by Lenti-RT activity assay [PMID: 17576848]
CCRF-CEM EC50 35 nM Antiviral activity against wild type HIV2 ROD infected in human CEM cells assessed as inhibition of virus production after 7 days by Lenti-RT activity assay [PMID: 17576848]
HEK293 EC50 2.8 nM Antiviral activity against wild type HIV1 NL4-3 in HEK293 cells after 48 hrs by replication-deffective luciferase reporter gene-based phenotypic assay [PMID: 17638694]
HEK-293T EC50 160 nM Antiviral activity against multidrug-resistant HIV1 106-PR infected in HEK293T cells assessed as inhibition of viral replication after 4 days by beta-galactosidase reporter gene assay [PMID: 22148316]
HepG2 CC50 27.8 μM Cytotoxicity against human HepG2 cells assessed as reduction in cell viability after 5 days by XTT assay 10.1039/C1MD00147G
Huh-7 CC50 > 37.6 μM Cytotoxicity against human Huh-7 cells incubated for 1 hr by MTS assay [PMID: 32845145]
MT2 CC50 > 100 μM Cytotoxicity against human MT2 cells after 7 days by MTT assay [PMID: 20439612]
MT2 CC50 > 100 μM Cytotoxicity against human MT2 cells assessed as inhibition of p24 Gag protein expression by MTT assay [PMID: 17371811]
MT2 EC50 0.0026 μM Antiviral activity against HIV2 EHO in MT2 cells assessed as inhibition of p24 Gag protein expression by MTT assay [PMID: 17371811]
MT2 EC50 0.0049 μM Antiviral activity against HIV2 ROD in MT2 cells assessed as inhibition of p24 Gag protein expression by MTT assay [PMID: 17371811]
MT2 EC50 0.007 μM Antiviral activity against HIV1 LAI in MT2 cells assessed as inhibition of p24 Gag protein expression by MTT assay [PMID: 17371811]
MT2 EC50 0.028 μM Antiviral activity against HIV2 ROD infected in human MT2 cells by MTT assay [PMID: 20439612]
MT2 EC50 0.032 μM Antiviral activity against HIV1 LAI infected in human MT2 cells after 7 days by MTT assay [PMID: 18955518]
MT2 EC50 0.035 μM Antiviral activity against HIV2 EHO infected in human MT2 cells by MTT assay [PMID: 20439612]
MT2 EC50 0.039 μM Antiviral activity against HIV1 LAI infected in human MT2 cells by MTT assay [PMID: 20439612]

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In Vitro Studies

In differentiated mouse 3T3-L1 adipocytes, lopinavir increased the apoptotic/necrotic-cell endpoint after 24 h at 25 µM versus DMSO. The 12.5 µM monotherapy group was not marked significant. This cellular toxicity result does not establish clinical toxicity or a selective apoptosis mechanism. [1]

During adipocyte differentiation, 12.5 µM lopinavir reduced lipid accumulation and mouse lipid-droplet number, while droplet size showed no significant change. Representative human SGBS-cell staining also showed reduced lipid accumulation. These findings concern adipocyte function, rather than antiviral potency. [1]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

Lopinavir-associated adipocyte cell death

Cell-based study · Differentiated murine 3T3-L1 adipocytes [1]

Lopinavir alone increased the combined apoptotic/necrotic-cell endpoint at 25 µM versus DMSO; 12.5 µM was not marked significant. The assay does not establish a selective apoptosis mechanism.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Relative amount of apoptotic and necrotic cells versus vehicle control (set to 1)relative amount 25 µM: increased, *p<0.05; 12.5 µM: no significance mark. Mean ± SE; four independent experiments. Exact fold values not transcribed from bars.[1]

Literature-Reported Treatment Conditions

Treatment concentration
12.5 and 25 µM
Exposure duration
24 h
Method
Annexin V-FITC/propidium iodide flow cytometry
Vehicle
DMSO
Co-treatment
Selected results are lopinavir alone; combination comparators are not attributed to monotherapy.
Reported limits
Final DMSO fraction and compound lot/form analysis are not reported in the read experiment.
Methods and source locations

Compound reported in the paper: Lopinavir; Compound label in the paper: LPV

Compound-level research findings; not validation of A10537 or a clinical dosing recommendation.

Figure 5; Results: HIV PIs Induce Cell Death in Adipocytes; Methods: Analysis of Apoptosis and Statistical Analysis

Relative amount of apoptotic and necrotic cells versus vehicle control (set to 1): Annexin V-FITC/propidium iodide; at least 20,000 cells analyzed per treatment group per Methods. One-way ANOVA per shared statistics. — Figure 5 image and caption

Lopinavir effects on lipid accumulation during differentiation

Cell-based study · Murine 3T3-L1 adipocytes; human SGBS adipocytes for staining [1]

Lopinavir reduced lipid accumulation and murine lipid-droplet number during differentiation, without a significant change in droplet size. Amprenavir had little effect on accumulation and increased droplet size.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Mean lipid-droplet number per murine cellqualitative direction Reduced versus DMSO, ***p<0.001; mean ± SE, three independent experiments. No exact bar-derived counts.[1]
Murine lipid-droplet sizequalitative direction No significant effect of LPV; amprenavir increased size. No exact bar-derived diameter.[1]
Intracellular lipid accumulationqualitative staining Reduced staining with LPV in murine cells and human SGBS cells; human panels represent three individual experiments.[1]

Literature-Reported Treatment Conditions

Treatment concentration
12.5 µM
Exposure duration
3T3-L1 staining: 8 days; morphometry: two weeks; human SGBS staining: 10 days
Method
Concurrent treatment during differentiation; Oil Red O/Nile red staining and image morphometry
Vehicle
DMSO (Figure 6 control)
Co-treatment
Selected results are lopinavir alone; combination comparators are not attributed to monotherapy.
Reported limits
Final DMSO fraction and compound lot analysis not reported. Human images are representative, not a quantitative human effect estimate.
Methods and source locations

Compound reported in the paper: Lopinavir; Compound label in the paper: LPV

Compound-level research findings; not validation of A10537 or a clinical dosing recommendation.

Figure 6A–E; Results: Effects of HIV PIs on Intracellular Lipid Accumulation in Adipocytes; Methods: staining and quantitative lipid-droplet analysis

Mean lipid-droplet number per murine cell: Image morphometry after two weeks; one-way ANOVA per shared statistics. — Figure 6C and caption

Murine lipid-droplet size — Figure 6D and Results lipid accumulation subsection

Intracellular lipid accumulation — Figure 6A,B,E and caption

In Vivo Studies

In male mice given oral lopinavir, Cyp3a deletion markedly increased plasma exposure. Abcb1a/b deletion had a smaller effect, while Abcc2 deletion did not significantly increase exposure. Ritonavir increased exposure in wild-type mice but produced no significant increase in Cyp3a-null mice. These pharmacokinetic findings do not measure antiviral efficacy. [2]

Genotype and ritonavir effects on oral lopinavir exposure

Animal study · Male mice, >99% FVB background, 8–14 weeks; wild-type and Cyp3a/transporter knockout strains [2]

At the tested oral dose, Cyp3a deletion strongly increased lopinavir exposure. Abcb1a/b deletion had a smaller effect; Abcc2 deletion did not significantly increase exposure. Ritonavir markedly increased exposure in wild-type mice, with no significant increase in Cyp3a-null mice.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Plasma lopinavir AUC(0–24h), monotherapyAUC (µg·h/mL) Wild-type 0.054 ± 0.034; Abcb1a/b−/− 0.465 ± 0.316 (*p<0.05); Abcc2−/− 0.248 ± 0.249 (not significant); Cyp3a−/− 118 ± 52 (**p<0.01), all versus wild-type. Mean ± SD; n=3–4.[2]
Plasma lopinavir AUC(0–24h), with ritonavirAUC (µg·h/mL) Wild-type 57.4 ± 26.2 (p<0.01 versus same strain without ritonavir); Cyp3a−/− 148 ± 28 (not significant versus 118 ± 52 without ritonavir). Mean ± SD; n=3–4.[2]

Conditions shared by the study groups

Route
Oral gavage
Frequency
Single administration
Treatment course
24 h plasma pharmacokinetic assessment
Vehicle
Ethanol/propylene glycol 19:81 (v/v)
Study groups and reported outcomes
Group / doseComparatorObserved resultReference
Wild-type, lopinavir alone
Lopinavir 25 mg/kg		Wild-type lopinavir monotherapyAUC 0.054 ± 0.034 µg·h/mL; mean ± SD, n=3–4.[2]
Abcb1a/b-null, lopinavir alone
Lopinavir 25 mg/kg		Wild-type lopinavir monotherapyAUC 0.465 ± 0.316 µg·h/mL; 8.6-fold versus wild-type; p<0.05; mean ± SD, n=3–4.[2]
Abcc2-null, lopinavir alone
Lopinavir 25 mg/kg		Wild-type lopinavir monotherapyAUC 0.248 ± 0.249 µg·h/mL; no significant increase versus wild-type; mean ± SD, n=3–4.[2]
Cyp3a-null, lopinavir alone
Lopinavir 25 mg/kg		Wild-type lopinavir monotherapyAUC 118 ± 52 µg·h/mL; 2185-fold versus wild-type; p<0.01; mean ± SD, n=3–4.[2]
Wild-type, lopinavir with ritonavir
Lopinavir 25 mg/kg; ritonavir 25 mg/kg		Same-strain lopinavir monotherapyAUC 57.4 ± 26.2 µg·h/mL; 1063-fold versus monotherapy; p<0.01; mean ± SD, n=3–4.[2]
Cyp3a-null, lopinavir with ritonavir
Lopinavir 25 mg/kg; ritonavir 25 mg/kg		Same-strain lopinavir monotherapyAUC 148 ± 28 µg·h/mL; no significant increase versus monotherapy; mean ± SD, n=3–4.[2]
Wild-type, lopinavir alone
Model: Male Wild-type mice; >99% FVB; 8–14 weeks
Reported limits: Exact per-arm n not specified in Table 1.
Abcb1a/b-null, lopinavir alone
Model: Male Abcb1a/b−/− mice; >99% FVB; 8–14 weeks
Reported limits: Exact per-arm n not specified in Table 1.
Abcc2-null, lopinavir alone
Model: Male Abcc2−/− mice; >99% FVB; 8–14 weeks
Reported limits: Exact per-arm n not specified in Table 1.
Cyp3a-null, lopinavir alone
Model: Male Cyp3a−/− mice; >99% FVB; 8–14 weeks
Reported limits: Exact per-arm n not specified in Table 1.
Wild-type, lopinavir with ritonavir
Model: Male Wild-type mice; >99% FVB; 8–14 weeks
Reported limits: Exact per-arm n not specified in Table 1.
Cyp3a-null, lopinavir with ritonavir
Model: Male Cyp3a−/− mice; >99% FVB; 8–14 weeks
Reported limits: Exact per-arm n not specified in Table 1.
Methods and source locations

Compound reported in the paper: Lopinavir; Compound label in the paper: Lopinavir

Compound-level research findings; not validation of A10537 or a clinical dosing recommendation.

Table 1 including footnotes; Results: Individual and combined impact; Effects of ritonavir co-administration; Methods: Animals, plasma pharmacokinetics, drug analysis, statistics, materials

Plasma lopinavir AUC(0–24h), monotherapy: LC-MS/MS; two-sided unpaired Student t-test. — Table 1, AUC(0–24h) column, vehicle and ritonavir arms; table footnotes and associated Results

Plasma lopinavir AUC(0–24h), with ritonavir: LC-MS/MS; two-sided unpaired Student t-test. — Table 1, AUC(0–24h) column, vehicle and ritonavir arms; table footnotes and associated Results

Wild-type, lopinavir alone · Table 1, AUC(0–24h) column, vehicle and ritonavir arms; table footnotes and associated Results

Abcb1a/b-null, lopinavir alone · Table 1, AUC(0–24h) column, vehicle and ritonavir arms; table footnotes and associated Results

Abcc2-null, lopinavir alone · Table 1, AUC(0–24h) column, vehicle and ritonavir arms; table footnotes and associated Results

Cyp3a-null, lopinavir alone · Table 1, AUC(0–24h) column, vehicle and ritonavir arms; table footnotes and associated Results

Wild-type, lopinavir with ritonavir · Table 1, AUC(0–24h) column, vehicle and ritonavir arms; table footnotes and associated Results

Cyp3a-null, lopinavir with ritonavir · Table 1, AUC(0–24h) column, vehicle and ritonavir arms; table footnotes and associated Results

Specifications

Manufacturer Adooq Bioscience
Actions Inhibitor
CAS Number 192725-17-0
Applications HIV Protease inhibitor
Formula C37H48N4O5
Molecular Weight 628.8
Synonyms ABT-378
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

Storage & Solubility

In Vitro Solubility

Reported Solubility

SolventReported Solubility
DMSO 116 mg/mL (184.48 mM)
Water Insoluble
Ethanol 116 mg/mL (184.48 mM)

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

In Vivo Preparation

Concentration
28 mg/mL
Vehicle
30% PEG400+0.5% Tween80+5% propylene glycol

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

  1. [1] Zha BS, Wan X, Zhang X, et al. HIV protease inhibitors disrupt lipid metabolism by activating endoplasmic reticulum stress and inhibiting autophagy activity in adipocytes. PloS one (2013). PMID: 23533630 DOI: 10.1371/journal.pone.0059514 Source material
  2. [2] van Waterschoot RA, ter Heine R, Wagenaar E, et al. Effects of cytochrome P450 3A (CYP3A) and the drug transporters P-glycoprotein (MDR1/ABCB1) and MRP2 (ABCC2) on the pharmacokinetics of lopinavir. British journal of pharmacology (2010). PMID: 20590614 DOI: 10.1111/j.1476-5381.2010.00759.x Source material

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