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Compound Detail

CHEMBL163

RITONAVIR
💊 Approved Drug
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💊 Approved Drug
CC(C)c1nc(CN(C)C(=O)N[C@H](C(=O)N[C@@H](Cc2ccccc2)C[C@H](O)[C@H](Cc2ccccc2)NC(=O)OCc2cncs2)C(C)C)cs1

Basic Information

ChEMBL ID CHEMBL163
Name RITONAVIR
Phase Approved
Structure Type MOL
InChI Key NCDNCNXCDXHOMX-XGKFQTDJSA-N
Therapeutic ✓ Yes

Known Names

A-84538 ABBOTT-84538 ABT-538 Empetus Norvir NSC-693184 Ritomune Ritonavir Ritonavir component of kaletra Ritonavir component of paxlovid Ritonavir component of technivie Ritonavir component of viekirax +7 more
46
Targets
248
Activities
4
Assay Types
30
PK Parameters
20
Publications
19
Known Names
20
Indications
2
Mechanisms

Molecular Properties

721.0
MW (Da)
5.91
ALogP
9
HBA
4
HBD
145.8
PSA (Ų)
0.11
QED
2
Ro5 Violations
17
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1996
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral

Flags

Black Box Warning Natural Product
USAN Stem -vir
USAN Year 1995

Extended Properties

Molecular Formula C37H48N6O5S2
MW 720.96
Aromatic Rings 4
Heavy Atoms 50
NP-Likeness -0.62

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Human immunodeficiency virus type 1 protease inhibitor INHIBITOR Human immunodeficiency virus type 1 protease
Cytochrome P450 3A inhibitor INHIBITOR Cytochrome P450 3A

Indications

Hepatitis C Hepatitis C, Chronic HIV Infections HIV Infections Virus Diseases Acquired Immunodeficiency Syndrome Coronavirus Infections Coronavirus Infections Hepatitis D Infections Influenza, Human Pneumonia Severe Acute Respiratory Syndrome Severe Acute Respiratory Syndrome Hepatitis B, Chronic Mycobacterium avium-intracellulare Infection Neoplasms Neoplasms Post-Acute COVID-19 Syndrome Pregnancy

ATC Classification

J05AE03
ritonavir
Level 1: ANTIINFECTIVES FOR SYSTEMIC USE
Level 2: ANTIVIRALS FOR SYSTEMIC USE

Drug Warnings

Black Box Warning
General Warning
Country: United States

Activity Summary

EC50 122 meas. best 10.26
IC50 83 meas. best 9.22
Ki 40 meas. best 10.82
Kd 3 meas. best 9.22

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Human immunodeficiency virus type 1 protease
CHEMBL243
Ki 10.82 9.5012 0.0 17
Protease
CHEMBL2366517
Ki 10.47 9.77 0.0 4
Human immunodeficiency virus 1
CHEMBL378
EC50 10.26 7.118 0.1 94
Unchecked
CHEMBL612545
Ki 9.34 7.5667 0.5 6
Human immunodeficiency virus type 1 protease
CHEMBL243
Kd 9.22 9.22 0.6 2
Protease
CHEMBL2366517
IC50 9.22 7.115 0.6 2
MT2
CHEMBL614184
IC50 8.0 8.0 10.0 1
MT4
CHEMBL388
IC50 8.0 7.0833 10.0 3
Cytochrome P450 3A
CHEMBL2364675
Ki 7.89 7.89 13.0 1
Human immunodeficiency virus 1
CHEMBL378
IC50 7.82 6.8522 15.0 9
Cytochrome P450 3A4
CHEMBL340
IC50 7.8 7.0413 16.0 8
Cytochrome P450 2C9
CHEMBL3397
IC50 7.8 6.1633 16.0 3
Cytochrome P450 3A4
CHEMBL340
Ki 7.72 7.1633 19.0 3
Plasmodium yoelii yoelii
CHEMBL612328
IC50 7.47 7.47 34.2 1
Human immunodeficiency virus
CHEMBL613758
EC50 7.42 6.665 38.0 2
Liver microsomes
CHEMBL613373
IC50 7.4 7.4 40.0 1
MT4
CHEMBL388
EC50 7.16 6.5675 70.0 4
Thromboxane-A synthase
CHEMBL1835
IC50 7.12 7.12 76.0 1
Multidrug and toxin extrusion protein 1
CHEMBL1743126
IC50 7.1 6.0467 80.0 3
Human immunodeficiency virus 2
CHEMBL380
EC50 7.08 6.595 84.0 10
Cytochrome P450 3A5
CHEMBL3019
Ki 6.92 6.92 120.0 1
Cytochrome P450 3A
CHEMBL2364675
IC50 6.85 5.5775 140.0 4
NON-PROTEIN TARGET
CHEMBL3879801
EC50 6.85 6.85 140.0 1
Protease
CHEMBL2366517
EC50 6.82 6.82 150.0 1
Unchecked
CHEMBL612545
IC50 6.7 5.63 200.0 3
Human immunodeficiency virus 2
CHEMBL380
IC50 6.54 6.54 290.0 1
Solute carrier organic anion transporter family member 1B1
CHEMBL1697668
IC50 6.16 5.8375 700.0 4
Plasmodium falciparum
CHEMBL364
EC50 6.07 5.5883 850.0 6
Substance-K receptor
CHEMBL2327
Ki 6.06 6.06 874.0 1
Solute carrier organic anion transporter family member 1B1
CHEMBL1697668
Ki 5.89 5.89 1300.0 1
ATP-dependent translocase ABCB1
CHEMBL4302
IC50 5.82 5.0467 1500.0 6
UDP-glucuronosyltransferase 1A1
CHEMBL1287617
IC50 5.77 5.645 1700.0 2
Bile salt export pump
CHEMBL6020
IC50 5.76 5.685 1740.0 4
Cytochrome P450 2B6
CHEMBL4729
IC50 5.7 5.7 2000.0 1
Plasmodium vivax
CHEMBL613013
IC50 5.65 5.65 2233.0 1
Cytochrome P450 2D6
CHEMBL289
IC50 5.64 4.97 2300.0 2
Substance-K receptor
CHEMBL2327
IC50 5.58 5.58 2622.0 1
Solute carrier organic anion transporter family member 1B3
CHEMBL1743121
Ki 5.4 5.4 4000.0 1
Nuclear receptor subfamily 1 group I member 2
CHEMBL3401
EC50 5.4 5.4 4000.0 1
Trypanosoma brucei rhodesiense
CHEMBL612348
IC50 5.37 5.37 4300.0 1
Multidrug and toxin extrusion protein 2
CHEMBL1743127
IC50 5.36 4.99 4400.0 2
Solute carrier organic anion transporter family member 1B3
CHEMBL1743121
IC50 5.36 5.36 4400.0 1
Vasopressin V1a receptor
CHEMBL1889
Ki 5.3 5.3 4981.0 1
SARS-CoV-2
CHEMBL4303835
EC50 5.3 5.18 5000.0 2
Kappa-type opioid receptor
CHEMBL237
Ki 5.26 5.26 5462.0 1
Solute carrier organic anion transporter family member 2B1
CHEMBL1743124
Ki 5.23 5.23 5900.0 1
Solute carrier organic anion transporter family member 2B1
CHEMBL1743124
IC50 5.21 5.21 6100.0 1
Leishmania donovani
CHEMBL367
IC50 5.05 5.05 8970.0 1
Hepatitis delta virus
CHEMBL4888466
EC50 5.04 5.04 9100.0 1
Plasmodium falciparum
CHEMBL364
IC50 5.01 4.9 9664.0 2

Pharmacokinetic Data

Parameter Value Units Species
AUC 3530.0 ng.hr.mL-1 Rattus norvegicus
AUC 8060.0 ng.hr.mL-1 Rattus norvegicus
AUC 2570.0 ng.hr.mL-1 Rattus norvegicus
AUC 5100.0 ng.hr.mL-1 Homo sapiens
AUC 8800.0 ng.hr.mL-1 Canis lupus familiaris
AUC 1560.0 ng.hr.mL-1 Canis lupus familiaris
AUC 6399.9 ng.hr.mL-1 Homo sapiens
AUC 3530.0 ng.hr.mL-1 Rattus norvegicus
AUC 8060.0 ng.hr.mL-1 Canis lupus familiaris
AUC 2190.0 ng.hr.mL-1 Canis lupus familiaris
AUC 4430.0 ng.hr.mL-1 Canis lupus familiaris
AUC 68000.0 ng.hr.mL-1 Homo sapiens
AUC 65300.0 ng.hr.mL-1 Homo sapiens
AUC 7810.0 ng.hr.mL-1 Homo sapiens
AUC 65900.0 ng.hr.mL-1 Homo sapiens
AUC 6430.0 ng.hr.mL-1 Homo sapiens
AUC 58400.0 ng.hr.mL-1 Homo sapiens
AUC 2.19 ug ml-1 Canis lupus familiaris
AUC 9600.0 ng.hr.mL-1 Homo sapiens
AUC 8190.0 ng.hr.mL-1 Homo sapiens
AUC 7270.0 ng.hr.mL-1 Homo sapiens
AUC 4270.0 ng.hr.mL-1 Homo sapiens
AUC 3293.0 ng.hr.mL-1 Homo sapiens
AUC 7773.0 ng.hr.mL-1 Homo sapiens
AUC 3584.0 ng.hr.mL-1 Homo sapiens
AUC 298001.61 ng.hr.mL-1 Homo sapiens
AUC 3530.0 ng.hr.mL-1 Rattus norvegicus
CL 1.2 mL.min-1.kg-1 Homo sapiens
CL 1.2 mL.min-1.kg-1 Homo sapiens
CL 1.2 mL.min-1.kg-1 Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Human immunodeficiency virus type 1 protease Ki = 0.015 nM 10.82 Inhibition constant of ritonavir towards HIV protease was determined -
Human immunodeficiency virus type 1 protease Ki = 0.015 nM 10.82 Tested for inhibitor binding of wild-type HIV PR 15056001
Human immunodeficiency virus type 1 protease Ki = 0.015 nM 10.82 Binding affinity to HIV1 protease assessed as inhibition constant 26799988
Human immunodeficiency virus type 1 protease Ki = 0.02 nM 10.7 Inhibitory activity against purified HIV protease -
Human immunodeficiency virus type 1 protease Ki = 0.02 nM 10.7 Inhibition of HIV protease 10866371
Protease Ki = 0.034 nM 10.47 Inhibition of HIV1 protease 17638694
Human immunodeficiency virus 1 EC50 = 0.055 nM 10.26 The activity against mutant HIV molecular clone wt (pNL4-3) was determined -
Human immunodeficiency virus type 1 protease Ki = 0.062 nM 10.21 Dissociation constant obtained by inhibition of Wild-type protease 10978186
Protease Ki = 0.098 nM 10.01 Inhibition of HIV1 protease 17981045
Human immunodeficiency virus type 1 protease Ki = 0.12 nM 9.92 Tested for inhibitor binding of D25N/V82A mutant of HIV PR 15056001
Human immunodeficiency virus 1 EC50 = 0.23 nM 9.64 The activity against mutant HIV molecular clone V82A was determined -
Human immunodeficiency virus 1 EC50 = 0.308 nM 9.51 The activity against mutant HIV molecular clone V82F was determined -
Human immunodeficiency virus 1 EC50 = 0.316 nM 9.5 The activity against mutant HIV molecular clone V82T was determined -
Protease Ki = 0.314 nM 9.5 Inhibition of HIV1 protease using fluorogenic hexapeptide substrate (2-aminobenz... -
Human immunodeficiency virus type 1 protease Ki = 0.37 nM 9.43 Binding affinity for HIV -1 Protease 10576691
Human immunodeficiency virus type 1 protease Ki = 0.37 nM 9.43 Binding affinity to inhibit the purified wild-type HIV-1 Protease 9003516
Human immunodeficiency virus type 1 protease Ki = 0.37 nM 9.43 Affinity against HIV protease 9406598
Human immunodeficiency virus type 1 protease Ki = 0.37 nM 9.43 Inhibitory activity against HIV-1 protease 8863807
Unchecked Ki = 0.46 nM 9.34 Inhibition of HIV1 Protease M2 variant by FRET based assay 17696512
Human immunodeficiency virus type 1 protease Ki = 0.59 nM 9.23 Inhibition constant against HIV-1 Protease 12459011

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL3885881 Rattus norvegicus 320
- 10.5281/zenodo.13943903 ADMET 89
17101675 10.1128/aac.00690-06 Human immunodeficiency virus 1 33
18955518 10.1128/aac.00689-08 Human immunodeficiency virus 1 33
17646413 10.1128/aac.00526-07 Homo sapiens 30
17371811 10.1128/aac.01413-06 Human immunodeficiency virus 1 24
31732255 10.1016/j.ejmech.2019.111813 ADMET 19
16472241 10.2174/1570163043334794 Hepatotoxicity 18
17981045 10.1016/j.bmc.2007.10.062 Human immunodeficiency virus 1 17
- 10.1016/S0960-894X(97)00080-2 Rattus norvegicus 15
21051535 10.1124/dmd.110.034629 ADMET 15
18411323 10.1128/aac.01565-07 Homo sapiens 15
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
- 10.1016/S0960-894X(97)00080-2 Human immunodeficiency virus 1 14
18573930 10.1128/aac.00194-08 Homo sapiens 12
18378713 10.1128/aac.00911-07 Human immunodeficiency virus 1 12
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
16913714 10.1021/jm060561m Human immunodeficiency virus 1 11
18426195 10.1021/jm701555p Human immunodeficiency virus 1 11
12699389 10.1021/jm021012t ATP-dependent translocase ABCB1 10

Data from ChEMBL 36 via Core Engine