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Compound Detail

CHEMBL729

LOPINAVIR
💊 Approved Drug
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💊 Approved Drug
Cc1cccc(C)c1OCC(=O)N[C@@H](Cc1ccccc1)[C@@H](O)C[C@H](Cc1ccccc1)NC(=O)[C@H](C(C)C)N1CCCNC1=O

Basic Information

ChEMBL ID CHEMBL729
Name LOPINAVIR
Phase Approved
Structure Type MOL
InChI Key KJHKTHWMRKYKJE-SUGCFTRWSA-N
Therapeutic ✓ Yes

Known Names

A-157378-0 A-157378.0 ABT-378 Aluviran Koletra Lopinavir Lopinavir component of kaletra Lopinavir, (s-(2s,4s,5s))- Lopinavir- Lopinavirum
25
Targets
293
Activities
4
Assay Types
30
PK Parameters
20
Publications
10
Known Names
17
Indications
1
Mechanisms

Molecular Properties

628.8
MW (Da)
4.33
ALogP
5
HBA
4
HBD
120.0
PSA (Ų)
0.20
QED
1
Ro5 Violations
15
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2000
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral

Flags

Natural Product
USAN Stem -vir
USAN Year 1998

Extended Properties

Molecular Formula C37H48N4O5
MW 628.81
Aromatic Rings 3
Heavy Atoms 46
NP-Likeness -0.04

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Human immunodeficiency virus type 1 protease inhibitor INHIBITOR Human immunodeficiency virus type 1 protease

Indications

HIV Infections HIV Infections Acquired Immunodeficiency Syndrome Coronavirus Infections Coronavirus Infections Influenza, Human Pneumonia Severe Acute Respiratory Syndrome Severe Acute Respiratory Syndrome Infections Pregnancy Sarcoma, Kaposi Anus Neoplasms Hepatitis C Insulin Resistance Respiratory Distress Syndrome Tuberculosis

Activity Summary

EC50 173 meas. best 9.0
IC50 80 meas. best 9.0
Ki 37 meas. best 10.85
Kd 3 meas. best 10.0

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Protease
CHEMBL2366517
Ki 10.85 10.31 0.0 7
Human immunodeficiency virus type 1 protease
CHEMBL243
Ki 10.59 9.7209 0.0 11
Unchecked
CHEMBL612545
Ki 10.4 8.5155 0.0 11
Human immunodeficiency virus type 1 protease
CHEMBL243
Kd 10.0 10.0 0.1 1
Human immunodeficiency virus 1
CHEMBL378
IC50 9.0 7.3532 1.0 19
Human immunodeficiency virus 1
CHEMBL378
EC50 9.0 7.0268 1.0 136
Protease
CHEMBL2366517
Kd 8.96 8.96 1.1 1
Protease
CHEMBL2366517
IC50 8.6 7.85 2.5 4
Human immunodeficiency virus 2
CHEMBL380
EC50 8.59 7.5307 2.6 15
Human immunodeficiency virus 2
CHEMBL380
IC50 8.4 6.9922 4.0 27
Unchecked
CHEMBL612545
IC50 7.8 7.7 16.0 2
Human immunodeficiency virus type 1 protease
CHEMBL243
IC50 7.6 7.6 25.0 1
NON-PROTEIN TARGET
CHEMBL3879801
IC50 7.52 6.12 30.0 2
Human immunodeficiency virus
CHEMBL613758
EC50 7.5 6.63 32.0 3
MT4
CHEMBL388
IC50 7.46 6.5025 35.0 4
Human immunodeficiency virus
CHEMBL613758
IC50 7.4 6.9 40.0 2
MT4
CHEMBL388
EC50 7.0 6.996 100.0 5
Cytochrome P450 3A4
CHEMBL340
Ki 6.39 6.13 410.0 3
Protease
CHEMBL2366517
EC50 5.94 5.94 1160.0 1
ATP-dependent translocase ABCB1
CHEMBL4302
IC50 5.77 5.38 1700.0 2
Plasmodium falciparum
CHEMBL364
IC50 5.72 5.645 1920.0 2
Plasmodium falciparum
CHEMBL364
EC50 5.7 5.64 2000.0 3
SARS-CoV-2
CHEMBL4303835
EC50 5.3 4.925 5000.0 4
Human coronavirus 229E
CHEMBL613837
EC50 5.18 5.18 6600.0 2
Broad substrate specificity ATP-binding cassette transporter ABCG2
CHEMBL5393
IC50 5.12 5.12 7600.0 1
Middle East respiratory syndrome-related coronavirus
CHEMBL4296578
EC50 5.1 5.1 8000.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 5.07 5.07 8511.4 1
SARS-CoV-2
CHEMBL4303835
IC50 5.04 4.8175 9120.0 4
Replicase polyprotein 1ab
CHEMBL4523582
IC50 5.04 5.04 9120.0 1
Trypanosoma brucei rhodesiense
CHEMBL612348
IC50 4.97 4.97 10810.0 1
Leishmania donovani
CHEMBL367
IC50 4.93 4.93 11830.0 1
Trypanosoma cruzi
CHEMBL368
IC50 4.81 4.81 15380.0 1
SARS-CoV
CHEMBL4303836
EC50 4.77 4.77 17100.0 2
Bile salt export pump
CHEMBL6020
IC50 4.76 4.76 17300.0 2
CAAX prenyl protease 1 homolog
CHEMBL1075286
IC50 4.74 4.74 18400.0 1
ATP-binding cassette sub-family C member 3
CHEMBL5918
IC50 4.68 4.68 21000.0 1
Unchecked
CHEMBL612545
EC50 4.58 4.58 26630.0 1
ATP-binding cassette sub-family C member 4
CHEMBL1743128
IC50 4.33 4.33 47000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 9280.0 ng.hr.mL-1 Rattus norvegicus
AUC 11260.0 ng.hr.mL-1 Canis lupus familiaris
AUC 99700.0 ng.hr.mL-1 Homo sapiens
AUC 59726.0 ng.hr.mL-1 Homo sapiens
AUC 48465.0 ng.hr.mL-1 Homo sapiens
AUC 157200.0 ng.hr.mL-1 Homo sapiens
AUC 151810.0 ng.hr.mL-1 Homo sapiens
AUC 99603.5 ng.hr.mL-1 Homo sapiens
AUC 9280.0 ng.hr.mL-1 Rattus norvegicus
CL 2.58 L/hr Homo sapiens
CL 2.61 L/hr Homo sapiens
CL 544.0 mL.min-1.g-1 Homo sapiens
CL 1.6 mL.min-1.g-1 Homo sapiens
CL 2.7 mL.min-1.g-1 Homo sapiens
Cmax 159.03 nM -
Cmax 8746.68 nM -
Cmax 2464.97 nM Rattus norvegicus
Cmax 3975.76 nM Canis lupus familiaris
Cmax 17763.71 nM Homo sapiens
Cmax 10888.82 nM Homo sapiens
Cmax 8352.28 nM Homo sapiens
Cmax 27353.25 nM Homo sapiens
Cmax 25524.4 nM Homo sapiens
Cmax 159030.55 nM Homo sapiens
Cmax 8746680.24 nM Homo sapiens
T1/2 8.21 hr Homo sapiens
T1/2 6.56 hr Homo sapiens
T1/2 0.22 hr Bos taurus
T1/2 101.0 hr -
T1/2 5.4 hr -

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Protease Ki = 0.014 nM 10.85 Inhibition of HIV1 protease 17638694
Protease Ki = 0.016 nM 10.8 Inhibition of HIV1 protease 17981045
Protease Ki = 0.018 nM 10.74 Inhibition of wild-type HIV1 BH10 protease expressed in Escherichia coli by spec... 18598016
Human immunodeficiency virus type 1 protease Ki = 0.026 nM 10.59 Inhibition of HIV1 recombinant protease D30N/N88D mutant expressed in Escherichi... 18598016
Human immunodeficiency virus type 1 protease Ki = 0.029 nM 10.54 Inhibition of HIV1 recombinant protease M46I/A71V/V82T/I84V mutant expressed in ... 18598016
Human immunodeficiency virus type 1 protease Ki = 0.029 nM 10.54 Inhibition of HIV1 recombinant protease L10I/I15V/E35D/N37S/R41K/I62V/L63P/A71V/... 18598016
Protease Ki = 0.0371 nM 10.43 Inhibition of HIV1 protease using fluorogenic hexapeptide substrate (2-aminobenz... -
Human immunodeficiency virus type 1 protease Ki = 0.04 nM 10.4 Inhibition of HIV1 protease D30N/L63P/N88D mutant 17149864
Unchecked Ki = 0.04 nM 10.4 Inhibition of HIV1 Protease M2 variant by FRET based assay 17696512
Protease Ki = 0.051 nM 10.29 Inhibition of HIV1 NL4-3 protease I84V mutant expressed in Escherichia coli TAP-... 32672965
Human immunodeficiency virus type 1 protease Ki = 0.06 nM 10.22 Inhibition of HIV1 recombinant protease A71V/V82T/I84V mutant expressed in Esche... 18598016
Protease Ki = 0.061 nM 10.21 Inhibition of HIV1 NL4-3 protease I50V/A71V mutant expressed in Escherichia coli... 32672965
Human immunodeficiency virus type 1 protease Ki = 0.08 nM 10.1 Inhibition constant for human immunodeficiency virus type 1 protease 15537350
Human immunodeficiency virus type 1 protease Kd = 0.1 nM 10.0 Binding affinity for human immunodeficiency virus type 1 protease 15537350
Human immunodeficiency virus type 1 protease Ki = 0.44 nM 9.36 Inhibition of HIV1 recombinant protease L10I/L24I/L33F/M46L/I54V/L63P/A71V/V82A/... 18598016
Human immunodeficiency virus type 1 protease Ki = 0.5 nM 9.3 Inhibition of HIV1 recombinant protease L10F/L19I/K20R/L33F/E35D/M36I/R41K/F53L/... 18598016
Unchecked Ki = 0.9 nM 9.05 Inhibition of HIV1 Protease M3 variant by FRET based assay 17696512
Human immunodeficiency virus type 1 protease Ki = 0.9 nM 9.05 Inhibition of HIV1 protease L10I/L63P/A71V/G73S/I84V/L90M mutant 17149864
Unchecked Ki = 0.9 nM 9.05 Inhibition of multidrug resistant HIV1 protease L101I, L36P, A71V, G73S, I84V, L... 20958050
Human immunodeficiency virus 1 IC50 = 1.0 nM 9.0 Antiviral activity against HIV1 isolate 5512 with V321 and M46L mutation in CBMC... 17116674

Literature References

PubMed DOI Target Context # Activities
17638694 10.1128/aac.00149-07 Human immunodeficiency virus 1 53
18227188 10.1128/aac.01284-07 Human immunodeficiency virus 2 36
17101675 10.1128/aac.00690-06 Human immunodeficiency virus 1 33
18955518 10.1128/aac.00689-08 Human immunodeficiency virus 1 33
26799988 10.1021/acs.jmedchem.5b01697 Human immunodeficiency virus 1 32
20308382 10.1128/aac.01784-09 Human immunodeficiency virus 1 31
18212102 10.1128/aac.01132-07 Human immunodeficiency virus 1 29
17371811 10.1128/aac.01413-06 Human immunodeficiency virus 1 24
19104010 10.1128/aac.00984-08 Human immunodeficiency virus 1 23
28418652 10.1021/acs.jmedchem.7b00172 Human immunodeficiency virus 1 21
20439612 10.1128/aac.01766-09 Human immunodeficiency virus 1 18
17576848 10.1128/aac.00146-07 Human immunodeficiency virus 2 17
17981045 10.1016/j.bmc.2007.10.062 Human immunodeficiency virus 1 17
19746963 10.1021/jm900695w Human immunodeficiency virus 1 13
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
18411323 10.1128/aac.01565-07 Homo sapiens 10
21149628 10.1128/aac.01228-10 Human immunodeficiency virus 1 10
19237646 10.1128/aac.01091-08 Serum 10
20404123 10.1128/aac.01828-09 Human immunodeficiency virus 1 10
20028821 10.1128/aac.01512-09 Plasmodium falciparum 10

Data from ChEMBL 36 via Core Engine