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Compound Detail

CHEMBL1324

TOLCAPONE
💊 Approved Drug
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💊 Approved Drug
Cc1ccc(C(=O)c2cc(O)c(O)c([N+](=O)[O-])c2)cc1
ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID CHEMBL1324
Name TOLCAPONE
Phase Approved
Structure Type MOL
InChI Key MIQPIUSUKVNLNT-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

RO 40-7592 RO-40-7592 RO-407592 Tasmar Tolcapona Tolcapone
13
Targets
51
Activities
3
Assay Types
30
PK Parameters
20
Publications
6
Known Names
14
Indications
1
Mechanisms

Molecular Properties

273.2
MW (Da)
2.55
ALogP
5
HBA
2
HBD
100.7
PSA (Ų)
0.39
QED
0
Ro5 Violations
3
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1997
Availability Prescription
Chirality Achiral

Routes of Administration

Oral

Flags

Black Box Warning Withdrawn Natural Product
USAN Stem -capone
USAN Year 1993

Extended Properties

Molecular Formula C14H11NO5
MW 273.24
Aromatic Rings 2
Heavy Atoms 20
NP-Likeness -0.51

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Catechol O-methyltransferase inhibitor INHIBITOR Catechol O-methyltransferase ✓ ✓

Indications

Liver Failure Parkinson Disease Alcoholism Alcoholism Brain Injuries Gambling Obsessive-Compulsive Disorder Pick Disease of the Brain Schizophrenia Tobacco Use Disorder Cocaine-Related Disorders Neuroblastoma Amyloid Neuropathies, Familial Executive Function

ATC Classification

N04BX01
tolcapone
Level 1: NERVOUS SYSTEM
Level 2: ANTI-PARKINSON DRUGS

Drug Warnings

Withdrawn
hepatotoxicity
Hepatotoxicity
Country: European Union; Portugal; Ireland; Australia; Canada; United Kingdom   Year: 1998
Withdrawn
hepatotoxicity
Hepatotoxicity
Country: European Union; Portugal; Ireland; Australia; Canada; United Kingdom   Year: 1998
Withdrawn
hepatotoxicity
hepatotoxic effects
Country: European Union; Portugal; Ireland; Australia; Canada; United Kingdom   Year: 1998
Withdrawn
hepatotoxicity
Hepatotoxicity
Country: European Union; Portugal; Ireland; Australia; Canada; United Kingdom   Year: 1998
Withdrawn
hepatotoxicity
hepatotoxic effects
Country: European Union; Portugal; Ireland; Australia; Canada; United Kingdom   Year: 1998
Black Box Warning
hepatotoxicity
Country: United States

Activity Summary

IC50 35 meas. best 9.04
Kd 9 meas. best 7.69
EC50 7 meas. best 5.7

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Catechol O-methyltransferase
CHEMBL2372
 IC50 9.04 8.0567 0.9 9
Transthyretin
CHEMBL3194
 Kd 7.69 7.0989 20.6 9
Catechol O-methyltransferase
CHEMBL2023
 IC50 6.9 6.9 127.0 1
Unchecked
CHEMBL612545
 IC50 6.58 5.6329 265.0 7
Genome polyprotein
CHEMBL5980
 IC50 6.19 6.19 640.0 5
Genome polyprotein
CHEMBL5419
 IC50 6.16 6.16 700.0 1
dengue virus type 2
CHEMBL613966
 EC50 5.7 5.655 2000.0 4
Transthyretin
CHEMBL3194
 IC50 5.5 5.01 3200.0 2
Genome polyprotein
CHEMBL5980
 EC50 5.15 5.15 7100.0 1
G-protein coupled receptor 35
CHEMBL1293267
 EC50 5.13 4.72 7440.0 2
ATP-binding cassette sub-family C member 4
CHEMBL1743128
 IC50 4.78 4.78 16700.0 1
Bile salt export pump
CHEMBL6020
 IC50 4.46 4.45 34500.0 2
Bile salt export pump
CHEMBL2073674
 IC50 4.33 4.33 47200.0 1
Krueppel-like factor 10
CHEMBL3407312
 IC50 4.3 4.3 50000.0 2
ATP-binding cassette sub-family C member 3
CHEMBL5918
 IC50 4.07 4.07 85000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 48849.85 ng.hr.mL-1 Homo sapiens
AUC 11927.5 ng.hr.mL-1 Mus musculus
CL 15.0 mL.min-1.kg-1 Rattus norvegicus
CL 3.3 mL.min-1.kg-1 Canis lupus familiaris
CL 2.7 mL.min-1.kg-1 Homo sapiens
CL 1.9 mL.min-1.kg-1 Homo sapiens
CL 1.9 mL.min-1.kg-1 Homo sapiens
CL - mL.min-1.kg-1 Homo sapiens
CL 1.9 mL.min-1.kg-1 Homo sapiens
CL 40.0 mL.min-1.g-1 Homo sapiens
CL 103.0 mL.min-1.g-1 Homo sapiens
CL - - Homo sapiens
CL 13.33 mL.min-1.kg-1 Mus musculus
Cmax 20000.0 nM Homo sapiens
Cmax 27876.59 nM Mus musculus
Fu 0.0012 - Homo sapiens
Fu 0.003 - Homo sapiens
Fu 0.003 - Macaca fascicularis
Fu 0.05 - Canis lupus familiaris
Fu 0.002 - Cavia porcellus
Fu 0.002 - Mus musculus
Fu 0.007 - Rattus norvegicus
Fu 0.39 - Homo sapiens
Fu - - Homo sapiens
Fu 0.001 - Rattus norvegicus
MRT 1.1 hr Homo sapiens
T1/2 1.1 hr Homo sapiens
T1/2 1.4 hr Mus musculus
Tmax 0.25 hr Mus musculus
Vd 1.6 L.kg-1 Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Catechol O-methyltransferase IC50 = 0.912 nM 9.04 Inhibition of MB-COMT in Wistar rat brain assessed as metanephrine formation pre... 27463695
Catechol O-methyltransferase IC50 = 0.91 nM 9.04 Inhibition of MB-COMT in Wistar rat brain assessed as metanephrine formation pre... 27463695
Catechol O-methyltransferase IC50 = 2.2 nM 8.66 Inhibition of rat COMT 26935940
Catechol O-methyltransferase IC50 = 2.2 nM 8.66 Inhibition of Catechol O-methyltransferase activity in rat brain 11806720
Catechol O-methyltransferase IC50 = 3.0 nM 8.52 Inhibition of MB-COMT in rat brain homogenates using adrenaline as substrate and... 36116233
Catechol O-methyltransferase IC50 = 17.0 nM 7.77 Inhibition of MB-COMT in rat liver homogenates using adrenaline as substrate and... 36116233
Transthyretin Kd = 20.6 nM 7.69 Binding affinity to transthyretin (unknown origin) by ITC method 30133284
Catechol O-methyltransferase IC50 = 30.59 nM 7.51 Inhibition of S-COMT in Wistar rat liver assessed as metanephrine formation prei... 27463695
Transthyretin Kd = 34.0 nM 7.47 Binding affinity to wild type TTR (unknown origin) assessed as gibbs free energy... 36306808
Transthyretin Kd = 34.0 nM 7.47 Binding affinity to wild type TTR (unknown origin) assessed as dissociation cons... 36306808
Transthyretin Kd = 48.0 nM 7.32 Binding affinity to wild-type TTR (unknown origin) expressed in Escherichia coli... 37837673
Transthyretin Kd = 50.0 nM 7.3 Binding affinity to TTR V122I mutant (unknown origin) expressed in Escherichia c... 37837673
Catechol O-methyltransferase IC50 = 53.0 nM 7.28 Inhibition of S-COMT in rat liver homogenates using adrenaline as substrate and ... 36116233
Transthyretin Kd = 56.0 nM 7.25 Binding affinity to transthyretin V122I mutant (unknown origin) by ITC method 30133284
Transthyretin Kd = 95.0 nM 7.02 Binding affinity to TTR V30M mutant (unknown origin) by isothermal titration cal... 34547896
Catechol O-methyltransferase IC50 = 127.0 nM 6.9 Inhibition of human recombinant His-tagged soluble COMT expressed in Escherichia... 27074629
Unchecked IC50 = 264.97 nM 6.58 PubChem BioAssay. GSK3B-pretreated HCT116 viability from Cell TiterGlo-IC50. (... -
Transthyretin Kd = 440.0 nM 6.36 Binding affinity to TTR V30M mutant (unknown origin) expressed in Escherichia co... 37837673
Genome polyprotein IC50 = 640.0 nM 6.19 Inhibition of Dengue Virus 4 recombinant NS2B-NS3 protease expressed in Escheric... 34601454
Genome polyprotein IC50 = 640.0 nM 6.19 Inhibition of DENV2 NS2B-NS3 serine protease expressed using Benzoyl-Nle-Lys-Arg... 31128447

Literature References

PubMed DOI Target Context # Activities
20334432 10.1021/jm1001524 Rattus norvegicus 16
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
11806720 10.1021/jm0109964 Catechol O-methyltransferase 13
37837673 10.1016/j.ejmech.2023.115837 Transthyretin 13
16335931 10.1021/jm0580454 Catechol O-methyltransferase 13
34547896 10.1021/acs.jmedchem.1c00823 Transthyretin 13
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
30133284 10.1021/acs.jmedchem.8b00817 Transthyretin 10
15646539 10.1016/s0399-8320(04)95062-2 NON-PROTEIN TARGET 8
36306808 10.1021/acs.jmedchem.2c01195 Transthyretin 8
27463695 10.1021/acs.jmedchem.6b00666 No relevant target 7
37837673 10.1016/j.ejmech.2023.115837 ADMET 7
32038769 10.1021/acsmedchemlett.9b00345 ADMET 6
- 10.1039/C2MD20210G G-protein coupled receptor 35 6
- 10.6019/CHEMBL4495565 SARS-CoV-2 6
30272964 10.1021/acs.jmedchem.8b01126 ADMET 6
21474681 10.1124/dmd.111.038778 Brain 5
15566291 10.1021/jm040848o Catechol O-methyltransferase 5
18426954 10.1124/dmd.108.020479 ADMET 4
34601454 10.1016/j.bmc.2021.116415 Genome polyprotein 4

Data from ChEMBL 36 via Core Engine