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Compound Detail

CHEMBL220492

TOPIRAMATE
💊 Approved Drug
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💊 Approved Drug
CC1(C)O[C@@H]2[C@@H](CO[C@@]3(COS(N)(=O)=O)OC(C)(C)O[C@@H]23)O1

Basic Information

ChEMBL ID CHEMBL220492
Name TOPIRAMATE
Phase Approved
Structure Type MOL
InChI Key KJADKKWYZYXHBB-XBWDGYHZSA-N
Therapeutic ✓ Yes

Known Names

(-)-topiramate Epitoma Epitomax Eprontia MCN-4853 Qudexy Qudexy xr RWJ-17021 RWJ-17021-000 Sincronil Topamac Topamax +10 more
34
Targets
363
Activities
3
Assay Types
6
PK Parameters
20
Publications
22
Known Names
20
Indications
6
Mechanisms

Molecular Properties

339.4
MW (Da)
-0.40
ALogP
8
HBA
1
HBD
115.5
PSA (Ų)
0.74
QED
0
Ro5 Violations
3
Rot. Bonds

Drug Information

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

Routes of Administration

Oral

Flags

Natural Product
USAN Year 1987

Extended Properties

Molecular Formula C12H21NO8S
MW 339.37
Aromatic Rings 0
Heavy Atoms 22
NP-Likeness 1.16

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Carbonic anhydrase II inhibitor INHIBITOR Carbonic anhydrase 2
Carbonic anhydrase IV inhibitor INHIBITOR Carbonic anhydrase 4
Glutamate receptor ionotropic AMPA antagonist ANTAGONIST Glutamate receptor ionotropic AMPA
Glutamate receptor ionotropic kainate antagonist ANTAGONIST Glutamate receptor ionotropic kainate
GABA-A receptor; anion channel positive modulator POSITIVE MODULATOR GABA-A receptor; anion channel
Sodium channel alpha subunit blocker BLOCKER Sodium channel alpha subunit

Indications

Epilepsy Lennox Gastaut Syndrome Migraine Disorders Seizures Alcoholism Alcoholism Anxiety Bipolar Disorder Bulimia Cocaine-Related Disorders Dementia Depressive Disorder Diabetes Mellitus, Type 2 Epilepsies, Partial Epilepsy, Tonic-Clonic Essential Tremor Gambling Headache Hyperlipidemias Hypertension

ATC Classification

N03AX11
topiramate
Level 1: NERVOUS SYSTEM
Level 2: ANTIEPILEPTICS

Activity Summary

Ki 344 meas. best 9.06
IC50 15 meas. best 8.3
Kd 4 meas. best 7.86

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Carbonic anhydrase 7
CHEMBL2326
Ki 9.06 8.9024 0.9 21
Carbonic anhydrase 2
CHEMBL205
IC50 8.3 6.76 5.0 3
Carbonic anhydrase 2
CHEMBL205
Ki 8.3 7.8524 5.0 83
Carbonate dehydratase
CHEMBL3745586
Ki 8.18 8.18 6.6 1
Unchecked
CHEMBL612545
Ki 8.18 6.5368 6.6 37
Carbonic anhydrase 2
CHEMBL205
Kd 7.86 6.98 13.8 3
Carbonic anhydrase V
CHEMBL2111457
Ki 7.59 7.59 25.4 1
Carbonic anhydrase 5A, mitochondrial
CHEMBL4789
Kd 7.59 7.59 25.4 1
Alpha carbonic anhydrase
CHEMBL1075028
Ki 7.54 7.54 29.1 2
Carbonic anhydrase 5B, mitochondrial
CHEMBL3969
Ki 7.52 7.52 30.0 11
Astrosclerin-3
CHEMBL1944499
Ki 7.42 7.42 38.0 1
Carbonic anhydrase 6
CHEMBL3025
Ki 7.35 7.35 45.0 7
Carbonic anhydrase 13
CHEMBL2186
Ki 7.33 7.33 47.0 4
Carbonic anhydrase 13
CHEMBL3912
Ki 7.33 7.33 47.0 1
Carbonic anhydrase 4
CHEMBL281
Ki 7.27 7.27 54.0 5
Carbonic anhydrase 4
CHEMBL281
IC50 7.27 7.27 54.0 1
Carbonic anhydrase 1
CHEMBL261
Ki 7.25 6.6098 56.0 66
Carbonic anhydrase 9
CHEMBL3594
Ki 7.24 6.8896 58.0 25
Carbonic anhydrase 5A, mitochondrial
CHEMBL4789
Ki 7.2 6.9692 63.0 13
Carbonic anhydrase 15
CHEMBL5973
Ki 7.11 7.11 78.0 3
Carbonic anhydrase
CHEMBL5931
Ki 6.96 6.96 110.0 1
Carbonic anhydrase
CHEMBL6185
Ki 6.96 6.96 110.0 1
Carbonic anhydrase
CHEMBL3932
Ki 6.92 6.455 120.0 2
Carbonic anhydrase
CHEMBL4211
Ki 6.76 6.725 172.0 2
Carbonic anhydrase 1
CHEMBL261
IC50 6.6 6.6 250.0 1
Carbonic anhydrase
CHEMBL1649055
Ki 6.43 6.43 367.0 1
Carbonic anhydrase 2
CHEMBL1697676
Ki 6.43 6.43 367.0 2
Delta carbonic anhydrase
CHEMBL3097982
Ki 6.41 6.41 392.0 1
Carbonic anhydrase 2
CHEMBL6068
Ki 6.32 6.32 474.0 1
Beta-carbonic anhydrase 1
CHEMBL5631
Ki 6.21 6.21 610.0 2
Carbonic anhydrase, alpha family
CHEMBL3621035
Ki 6.11 6.11 769.0 1
Carbonic anhydrase
CHEMBL5337
Ki 5.96 5.96 1108.0 3
Unchecked
CHEMBL612545
IC50 5.87 5.2443 1360.0 7
Carbonic anhydrase 2
CHEMBL4706
IC50 5.85 5.85 1400.0 1
Carbonic anhydrase 14
CHEMBL3510
Ki 5.84 5.84 1460.0 12
PROBABLE TRANSMEMBRANE CARBONIC ANHYDRASE (CARBONATE DEHYDRATASE) (CARBONIC DEHYDRATASE)
CHEMBL5767
Ki 5.52 5.52 3020.0 1
Carbonic anhydrase 12
CHEMBL3242
Ki 5.42 5.2667 3800.0 3
Carbonic anhydrase 4
CHEMBL3729
Ki 5.31 5.31 4900.0 9
Carbonic anhydrase
CHEMBL3926
Ki 4.63 4.63 23500.0 1
Sodium channel protein type 2 subunit alpha
CHEMBL3399
IC50 4.01 4.01 97000.0 2

Pharmacokinetic Data

Parameter Value Units Species
F 70.0 % Homo sapiens
F 80.0 % Homo sapiens
Fu 0.79 - Rattus norvegicus
Fu 0.61 - Rattus norvegicus
T1/2 21.0 hr Homo sapiens
Vd 3.2 L.kg-1 Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Carbonic anhydrase 7 Ki = 0.87 nM 9.06 Inhibition of human carbonic anhydrase 7 by CO2 hydration assay 18406497
Carbonic anhydrase 7 Ki = 0.87 nM 9.06 Ki value against human carbonic anhydrase VII 15686895
Carbonic anhydrase 7 Ki = 0.9 nM 9.05 Inhibition of recombinant human CA7 incubated for 15 mins by phenol red dye base... 34216985
Carbonic anhydrase 7 Ki = 0.9 nM 9.05 Inhibition of recombinant human carbonic anhydrase 7 incubated for 15 mins prior... 28253618
Carbonic anhydrase 7 Ki = 0.9 nM 9.05 Inhibition of human recombinant carbonic anhydrase 7 preincubated for 15 mins by... 24287559
Carbonic anhydrase 7 Ki = 0.9 nM 9.05 Inhibition of human cytosolic carbonic anhydrase 7 preincubated for 15 mins at r... 23965175
Carbonic anhydrase 7 Ki = 0.9 nM 9.05 Inhibition of human cytosolic carbonic anhydrase 7 preincubated for 15 mins by s... 23867389
Carbonic anhydrase 7 Ki = 0.9 nM 9.05 Inhibition of human recombinant full length CA7-mediated CO2 hydration preincuba... 22443141
Carbonic anhydrase 7 Ki = 0.9 nM 9.05 Inhibition of human carbonic anhydrase 7 preincubated with compound for 15 mins ... 21506569
Carbonic anhydrase 7 Ki = 0.9 nM 9.05 Inhibition of human recombinant carbonic anhydrase 7 by stopped flow CO2 hydrati... 19435663
Carbonic anhydrase 7 Ki = 0.9 nM 9.05 Inhibition of human recombinant CAH7 21395315
Carbonic anhydrase 7 Ki = 0.9 nM 9.05 Inhibition of full length human carbonic anhydrase 7 preincubated for 15 mins by... 20472429
Carbonic anhydrase 7 Ki = 0.9 nM 9.05 Inhibition of human recombinant CA7 by stopped flow CO2 hydrase assay 20028100
Carbonic anhydrase 7 Ki = 0.9 nM 9.05 Inhibition of human cloned CA7 by stopped-flow CO2 hydration method 18640037
Carbonic anhydrase 7 Ki = 0.9 nM 9.05 Inhibition of human carbonic anhydrase 7 17475500
Carbonic anhydrase 7 Ki = 0.9 nM 9.05 Inhibition of human recombinant CA7 after 15 mins by CO2 hydration stopped flow ... 17376683
Carbonic anhydrase 7 Ki = 0.9 nM 9.05 Inhibition of human cloned CA7 by stopped-flow CO2 hydration method 17125255
Carbonic anhydrase 7 Ki = 0.9 nM 9.05 Inhibition of recombinant full length human carbonic anhydrase-7 assessed as red... 30530195
Carbonic anhydrase 7 Ki = 0.9 nM 9.05 Binding affinity to human recombinant carbonic anhydrase 7 assessed as inhibitio... 37436184
Carbonic anhydrase 2 Ki = 5.0 nM 8.3 Inhibition of cloned human carbonic anhydrase II 16134940

Literature References

PubMed DOI Target Context # Activities
16472241 10.2174/1570163043334794 Hepatotoxicity 18
19388676 10.1021/jm801432r Mus musculus 14
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
3572976 10.1021/jm00388a023 Mus musculus 13
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
9548821 10.1021/jm970790w Rattus norvegicus 8
9548821 10.1021/jm970790w Mus musculus 8
21332115 10.1021/jm1013242 Unchecked 8
15646539 10.1016/s0399-8320(04)95062-2 NON-PROTEIN TARGET 8
18572411 10.1016/j.bmc.2008.06.005 Aquaporin-4 7
18363349 10.1021/jm7015649 Carbonic anhydrase 2 6
15771438 10.1021/jm040124c Carbonic anhydrase 2 5
19388676 10.1021/jm801432r Rattus norvegicus 5
9548821 10.1021/jm970790w Unchecked 5
17646100 10.1016/j.bmcl.2007.07.019 Unchecked 4
21314129 10.1021/jm101525j Unchecked 4
9548821 10.1021/jm970790w No relevant target 4
11784136 10.1021/jm0109199 Mus musculus 4
19764786 10.1021/jm901036q Plasma 4
20201556 10.1021/jm901888x Unchecked 4

Data from ChEMBL 36 via Core Engine