a similarity-based classifier using topomers to provide a
TRANSCRIPT
1
SUPPORTING INFORMATION
A similarity-based classifier using topomers to provide a
knowledge base for hERG channel inhibition
Britta Nisius and Andreas H. Göller
Bayer HealthCare AG, Global Drug Discovery, Lead Generation and Optimization, Aprather Weg 18a,
D-42096 Wuppertal, Germany
2
Table S1: Descriptors used to validate the use of neighbors with a Topomer Search distance up to 270
Descriptor Characterization
Mol_weight Molecular weight
AlogP The octanol-water partition coefficient
AlogP_MR Estimate of molecular refractivity
Num_Atoms Total number of atoms
Num_Hydrogens Number of hydrogens
Num_PositiveAtoms Number of positively charged atoms
Num_NegativeAtoms Number of negatively charged atoms
Num_RotatableBonds Number of rotatable bonds
Num_Rings Number of rings
Molecular_SurfaceArea Total surface area using a 2D approximation
Molecular_FractionalPolarSurfaceArea Ratio of polar surface area divided by the total surface area
Molecular_Volume 3D volume based on 3D coordinates
3
Table S2: Dataset of 681 hERG patch-clamp measurements on mammalian cell lines (HEK, CHO,
COS) and corresponding references.
Name pIC50 Reference
(2R)-N-(4-tert-butylphenyl)-N'-cyano-4-(3-fluoropyridin-2-yl)-
2-methylpiperazine-1-carboximidamide 6.00 1
(4R)-4-(4-fluorophenyl)-8-[1-(4-fluorophenyl)cyclohexyl]-2,8-
diazaspiro[4.5]decan-1-one 5.89 1
(5aR,9R)-2,9-dimethyl-5,5a,6,7,8,9-
hexahydropyrido[3',2':4,5]pyrrolo[1,2-a]pyrazine 4.68 1
1,4-Dihydroindeno[1,2-c]pyrazol_50 5.28 2
1,4-Dihydroindeno[1,2-c]pyrazol_77 4.28 2
1,4-Dihydroindeno[1,2-c]pyrazol_85 5.77 2
1,4-Dihydroindeno[1,2-c]pyrazol_90 4.94 2
1-{4-[({4-[(4-bromo-2-fluorophenyl)amino]-6-
methoxyquinazolin-7-yl}oxy)methyl]piperidin-1-yl}-2-
(dimethylamino)ethanone 5.82 1
1-{4-[2-({4-[(2,3-dimethyl-1H-indol-5-yl)oxy]-6-
methoxyquinazolin-7-yl}oxy)ethyl]piperazin-1-yl}propan-2-one 5.00 1
1-bis(4-fluorophenyl)methyl piperazine 5.80 3
2-Amino-N-pyrimidin-4-ylacetamide-1 6.02 4
2-Amino-N-pyrimidin-4-ylacetamide-2 6.55 4
2-Amino-N-pyrimidin-4-ylacetamide-3 5.78 4
2-Amino-N-pyrimidin-4-ylacetamide-4 5.38 4
2-Amino-N-pyrimidin-4-ylacetamide-5 6.19 4
2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)
(Racemate) 4.00
3
2-hydroxymethyl olanzapine 4.94 5
2-hydroxymethyl olanzapine 4.94 3
2-hydroxymethyl olanzapine 4.92 6
4,4-difluorobenzhydrol 4.00 3
4,4-difluorobenzophenone 4.14 3
4-Aminopyridine 2.40 6
4
4-Aminopyridine 2.36 3
4-Aminopyridine 2.36 5
5-chloro-N-(2,4-dimethoxybenzyl)-1-benzofuran-2-
carboxamide 4.78 1
5-chloro-N-[3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-
yl)propyl]-N-methyl-1-benzofuran-2-carboxamide 4.70 1
6-(4-chlorophenyl)-3-{4-[(3S)-3-hydroxypyrrolidin-1-yl]-3-
methoxyphenyl}thieno[3,2-d]pyrimidin-4(3H)-one 5.00 1
6-(4-chlorophenyl)-3-{4-[(3S)-3-hydroxypyrrolidin-1-yl]-3-
methoxyphenyl}thieno[3,2-d]pyrimidin-4(3H)-one 5.35 1
9-hydroxyrisperidone 5.89 7
9-hydroxyrisperidone 6.00 6
AF 3013 (NM-394) 3.00 3
Ajmaline 5.98 3
Alfuzosin 4.08 7
Alosetron 5.52 5
Alosetron 5.50 5
Alosetron 5.50 7
Alosetron 5.49 1
Alosetron 5.49 3
Alosetron 5.49 8
Aminomethyl-tetrahydronaphthalene-ketopiperazine 1 5.09 9
Aminomethyl-tetrahydronaphthalene-ketopiperazine 2a 5.48 9
Aminomethyl-tetrahydronaphthalene-ketopiperazine 2b 5.77 9
Aminomethyl-tetrahydronaphthalene-ketopiperazine 2c 5.48 9
Aminomethyl-tetrahydronaphthalene-ketopiperazine 2d 5.92 9
Aminomethyl-tetrahydronaphthalene-ketopiperazine 4a 5.70 9
Aminomethyl-tetrahydronaphthalene-ketopiperazine 4b 5.40 9
Aminomethyl-tetrahydronaphthalene-ketopiperazine 4e 4.96 9
Aminomethyl-tetrahydronaphthalene-ketopiperazine 4f 4.89 9
Aminomethyl-tetrahydronaphthalene-ketopiperazine 4g 4.62 9
5
Aminomethyl-tetrahydronaphthalene-ketopiperazine 4h 4.60 9
Aminomethyl-tetrahydronaphthalene-ketopiperazine 4i 4.60 9
Amitriptyline 5.00 5
Amitriptyline 5.00 10
Amitriptyline 5.00 8
Amitriptyline 5.00 7
Amitriptyline 5.00 3
Amitriptyline 5.00 11
Amsacrine 6.68 1
Amsacrine 6.68 8
Amsacrine 6.68 3
Amsacrine 6.67 5
Aripiprazole 6.20 1
Articaine 3.65 12
Astemizole 8.00 10
Astemizole 9.05 7
Astemizole 9.04 11
Astemizole 9.04 5
Astemizole 8.89 1
Astemizole 8.89 1
Astemizole 7.94 8
Astemizole 7.89 1
Astemizole 7.68 1
Astemizole 9.05 3
Atenolol (Racemate) 3.00 3
AVE-0118 5.00 1
Azimilide 6.25 7
Azimilide 6.25 6
Azimilide 6.25 11
6
Azimilide 6.22 5
Azimilide 6.21 6
Azimilide 5.85 10
BAPTA-AM 5.88 13
BCTC 6.00 1
Benperidol 8.47 14
Benzoylecgonine 3.00 1
Benzoylecgonine 3.41 1
Bepridil 6.26 10
Bepridil 6.62 11
Bepridil 6.26 5
Bepridil 6.26 6
Bepridil 6.26 3
Bepridil 7.64 8
Bepridil 7.59 7
Berberine 5.51 3
Bicifadine 4.34 1
Bisindolylmaleimide 6.00 3
BMCL_03_13_1829-1835_1 7.06 3
BMCL_03_13_1829-1835_10 8.21 3
BMCL_03_13_1829-1835_12 4.00 3
BMCL_03_13_1829-1835_14 6.69 3
BMCL_03_13_1829-1835_15 7.96 3
BMCL_03_13_1829-1835_16 4.59 3
BMCL_03_13_1829-1835_17 5.83 3
BMCL_03_13_1829-1835_18 5.34 3
BMCL_03_13_1829-1835_19 5.71 3
BMCL_03_13_1829-1835_2 8.00 3
BMCL_03_13_1829-1835_20 4.80 3
7
BMCL_03_13_1829-1835_21 5.66 3
BMCL_03_13_1829-1835_22 5.46 3
BMCL_03_13_1829-1835_23 4.00 3
BMCL_03_13_1829-1835_3 8.15 3
BMCL_03_13_1829-1835_4 6.24 3
BMCL_03_13_1829-1835_5 4.12 3
BMCL_03_13_1829-1835_7 6.88 3
BMCL_03_13_1829-1835_8 7.44 3
BMCL_03_13_1829-1835_9 4.00 3
BMCL_2006_1207_19 5.46 15
BMCL131829-02 8.00 7
BMCL131829-05 5.13 7
BMCL131829-11 6.34 7
BMCL131829-16 4.59 7
BMCL131829-17 5.83 7
BRL-32872 7.70 3
BRL-32872 7.70 3
Brompheniramine 5.76 16
Brompheniramine maleate 6.05 16
Buprenorphine 5.10 6
Canrenoic Acid 3.98 7
Carbamazepine 2.52 17
Carvedilol 6.29 1
Carvedilol 6.29 3
Chlorobutanol 2.36 3
Chloroquine 5.60 1
Chloroquine 5.60 6
Chloroquine 5.60 5
Chloroquine 5.60 3
8
Chlorpheniramine 4.89 1
Chlorpheniramine 4.89 3
Chlorpromazine 5.83 5
Chlorpromazine 5.83 7
Chlorpromazine 5.83 11
Chlorpromazine 5.83 10
Chlorpromazine 5.60 8
Chlorpromazine 5.83 1
Chlorpromazine 5.81 1
Chlorpromazine 5.83 3
Chlorpromazine 5.81 3
Chromanolol 293B 4.26 18
Chromanolol 293B 5.18 15
Cibenzoline 5.43 3
Cimetidine 2.00 1
Ciprofloxacin 3.02 5
Ciprofloxacin 3.02 10
Ciprofloxacin 3.02 8
Ciprofloxacin 3.02 3
Ciprofloxacin 3.02 7
Ciprofloxacin 3.00 3
Citalopram 5.40 7
Citalopram 5.40 8
Citalopram 5.40 3
CJ-033466 5.59 19
Clarithromycin 4.48 1
Clarithromycin 4.04 1
Clebopride 6.21 20
Clemastine 7.92 21
9
Clenbuterol 4.10 5
Clomifene 6.74 5
Clomifene 6.74 8
Clozapine 6.59 8
Clozapine 6.50 7
Clozapine 6.49 1
Clozapine 6.49 3
Clozapine 6.49 6
Clozapine 5.60 1
Clozapine 5.35 5
Cocaethylene 5.92 1
Cocaine 5.36 1
Codeine 3.00 3
Codeine 3.52 5
Cyamemazine 6.33 3
Desbutyl-lumefantrine 5.26 6
Desipramine 6.00 6
Desipramine 5.86 5
Desipramine 5.86 8
Desipramine 5.86 7
Desipramine 5.86 3
Desmethylolanzapine 4.85 3
Desmethylastemizole 9.00 10
Desmethylastemizole 9.00 5
Desmethylastemizole 9.00 8
Desmethylastemizole 9.00 7
Desmethylastemizole 9.00 3
Diltiazem 4.77 5
Diltiazem 4.76 7
10
Diltiazem 4.76 11
Diltiazem 4.76 10
Diltiazem 4.76 8
Diphenhydramine 5.59 8
Disopyramide 5.14 7
Disopyramide 5.14 3
Dofetilide 8.00 1
Dofetilide 8.00 3
Dofetilide 8.00 7
Dofetilide 7.96 1
Dofetilide 7.96 3
Dofetilide 7.32 6
Dofetilide 8.02 3
Dofetilide 8.00 10
Dofetilide 7.92 1
Dofetilide 7.92 3
Dofetilide 7.92 6
Dofetilide 7.92 5
Dofetilide 7.91 11
Dofetilide 7.91 8
Dofetilide 7.82 1
Dofetilide 7.82 1
Dofetilide 7.82 3
Dolasetron 5.23 1
Dolasetron 5.07 1
Domperidone 6.79 1
Domperidone 6.79 3
Domperidone 6.79 7
Domperidone 6.79 8
11
Domperidone 6.79 5
Domperidone 6.79 11
Doxazosin 6.23 7
Doxazosin 6.23 5
Doxazosin 6.23 8
Doxazosin 6.23 3
Doxepin 5.19 22
Dronedarone 7.23 5
Droperidol 7.49 7
Droperidol 7.49 8
Droperidol 7.49 1
Droperidol 7.49 7
Droperidol 7.49 5
DW-224a 3.66 20
E-4031 8.06 3
E-4031 6.87 3
E-4031 6.87 6
E-4031 7.55 6
E-4031 8.11 3
E-4031 8.11 6
E-4031 8.11 11
E-4031 7.92 8
E-4031 7.74 6
E-4031 7.74 3
E-4031 7.74 7
E-4031 7.74 5
E-4031 7.58 6
Ecgoninemethylester 3.00 1
Ecgoninemethylester 3.38 1
12
EDDP(Edifenphos) 4.30 5
EGCG 5.22 23
Eliprodil 7.70 1
EMD-60263 5.18 15
ER-118585 7.40 3
Erythromycin 4.26 1
Erythromycin 4.23 1
Erythromycin 4.14 1
Erythromycin 4.02 1
Erythromycin 3.82 1
Erythromycin 3.80 1
Erythromycin 3.41 1
Erythromycylamine 3.56 7
Erythromycylamine 3.56 6
Erythromycylamine 3.43 1
Estradiol 4.00 3
Famotidine 5.00 1
Fentanyl 5.74 3
Fentanyl 5.75 5
Fexofenadine 4.64 7
Fexofenadine 4.64 3
Fexofenadine 4.67 5
Fexofenadine 4.67 10
Fexofenadine 4.67 8
Flecainide 5.41 5
Flecainide 5.41 8
Flecainide 5.41 7
Flecainide 5.41 1
Flecainide 5.41 6
13
Flecainide 5.41 3
Fluoxetine 5.82 7
Fluoxetine 6.34 8
Fluoxetine 5.82 3
Fluvoxamine 5.42 3
Fluvoxamine 5.50 3
Gatifloxacin 3.89 11
Gatifloxacin 3.89 10
Gatifloxacin 3.89 1
Gatifloxacin 3.89 7
Gatifloxacin 3.89 3
Gatifloxacin 3.89 5
Gatifloxacin 3.89 8
GF109203X 6.00 5
Grepafloxacin 4.36 5
Grepafloxacin 4.30 7
Grepafloxacin 4.30 10
Grepafloxacin 4.11 11
Grepafloxacin 4.30 3
Grepafloxacin 3.99 3
Halofantrine 6.71 5
Halofantrine 6.71 6
Halofantrine 6.70 11
Halofantrine 6.70 10
Halofantrine 7.67 7
Halofantrine 7.67 6
Halofantrine 7.51 8
Halofantrine 7.40 6
Haloperidol 7.73 1
14
Haloperidol 7.50 7
Haloperidol 7.49 1
Haloperidol 7.49 3
Haloperidol 7.72 8
Haloperidol 7.57 1
Haloperidol 7.57 3
Haloperidol 7.57 5
Haloperidol 7.57 6
Haloperidol 7.55 11
Haloperidol 7.52 10
Haloperidol 7.20 1
Haloperidol 7.20 3
Haloperidol 7.05 1
Haloperidol 6.76 1
Haloperidol 6.76 1
HY-2901 5.00 1
ICI 118551 5.04 3
Ifenprodil 7.00 1
Imipramine 5.47 11
Imipramine 5.47 5
Imipramine 5.47 10
Imipramine 5.47 8
Imipramine 5.47 7
Imipramine 5.47 3
Indometacin 3.52 1
Irbesartan 3.71 3
Irbesartan 3.71 7
Isradipine 5.00 5
Isradipine 4.00 3
15
Josamycin 3.99 6
Josamycin 3.99 1
Ketanserin 6.97 8
Ketoconazole 5.72 10
Ketoconazole 5.77 1
Ketoconazole 5.72 5
Ketoconazole 5.72 1
Ketoconazole 5.72 7
Ketoconazole 5.72 8
Ketoconazole 5.70 6
Ketoconazole 5.63 1
Ketoconazole 5.36 1
Ketoconazole 5.33 1
L-alpha-Acetylmethadol 5.61 6
Lamotrigine 3.64 5
Levofloxacin 3.04 5
Levofloxacin 3.04 10
Levofloxacin 3.04 7
Levofloxacin 3.04 1
Levofloxacin 2.85 8
Levofloxacin 3.37 1
Lidoflazine 7.80 3
Lidoflazine 7.43 1
Lidoflazine 7.80 8
Lidoflazine 7.79 5
Lidoflazine 7.78 6
Lignocaine 3.58 6
Lignocaine 3.58 7
Lignocaine 3.58 3
16
Lomefloxacin 2.62 24
Lopinavir 5.07 1
Loratadine 6.77 10
Loratadine 6.76 7
Loratadine 6.76 6
Loratadine 6.76 11
Loratadine 6.76 5
Loratadine 5.64 8
Loratadine 5.52 1
Loratadine 5.40 1
Loratadine 5.40 3
Loratadine 6.76 3
Lovastatine 5.15 1
Lumefantrine 5.09 1
Lumefantrine 5.10 5
Lumefantrine 5.09 8
Lumefantrine 5.09 6
LY-97241 8.66 1
LY-97241 8.66 1
M-43068 3.52 1
Maraviroc 5.00 1
MDL-74156 4.92 1
MDL-74156 5.07 1
Mefloquine 5.25 7
Mefloquine 5.25 5
Mefloquine 5.59 8
Mefloquine 5.58 6
Meperidine 4.12 3
Meperidine 4.13 5
17
Mepivacaine 3.81 3
Mesoridazine 6.49 1
Mesoridazine 6.36 15
Mesoridazine 6.49 3
Mesoridazine 6.26 3
Methadone 5.01 5
Methadone 5.00 6
Methadone 5.01 3
Methadone 4.70 3
Methylecgonidine 3.76 6
Metoclopramide 5.27 5
Metoprolol 3.84 3
Mexiletine 5.00 5
Mibefradil 6.00 6
Mibefradil 5.84 1
Mibefradil 5.84 11
Mibefradil 5.84 10
Mibefradil 5.96 1
Miconazole 5.68 1
Miconazole 5.68 3
Miconazole 5.68 5
Misolastine 6.36 8
Mizolastine 6.46 7
Mizolastine 6.46 6
Mizolastine 6.45 11
Mizolastine 6.36 10
Mizolastine 6.46 7
Mizolastine 6.46 5
MK-499 7.68 15
18
Morphine 3.00 3
Morphine 3.00 5
Mosapride 5.32 19
Moxifloxacin 3.93 11
Moxifloxacin 3.89 7
Moxifloxacin 4.13 6
N-{(1S)-2-[(3S)-3-hydroxypyrrolidin-1-yl]-1-phenylethyl}-N-
methyl-2-(4-{[(methylsulfonyl)amino]methyl}phenyl)acetamide 5.00 1
Naringenin 4.44 1
N-Demethylclozapine 5.35 1
N-Demethylerythromycin 3.83 6
N-Demethylolanzapine 4.85 6
N-Desbutylhalofantrine 7.14 6
N-Desbutylhalofantrine 7.14 7
N-Desbutylhalofantrine 7.14 5
N-Desbutylhalofantrine 7.14 8
N-Desbutylhalofantrine 7.14 3
N-Desmethylclozapine 5.35 15
Nelfinavir 4.94 1
Nicotine 3.61 1
Nifedipine 4.30 5
Nifedipine 4.30 10
Nifedipine 4.00 3
NIP-142 4.36 1
Nitrendipine 5.00 5
Nitrendipine 5.00 1
Nitrendipine 5.00 10
Noracetylmethadol 4.92 25
Norastemizole 7.56 5
19
Norastemizole 7.56 7
Norastemizole 7.55 8
Norastemizole 7.56 3
Norclozapine 5.35 7
Norclozapine 5.40 6
Norfluoxetine 5.64 1
Norfluoxetine 5.60 1
Olanzapine 5.22 3
Olanzapine 5.22 1
Olanzapine 6.74 10
Olanzapine 6.74 8
Olanzapine 6.64 6
Olanzapine 6.64 7
Olanzapine 6.64 1
Olanzapine 6.63 5
Ondansetron 6.09 10
Ondansetron 6.09 7
Ondansetron 6.09 6
Ondansetron 6.09 5
Ondansetron 6.09 8
Ondansetron 6.09 3
Orphenadrine 6.07 26
Oxatomide 6.45 1
Paliperidone 5.89 1
Perhexiline 5.11 5
Perhexiline 5.11 10
Perhexiline 5.11 8
Perhexiline 5.11 7
Perhexiline 5.11 3
20
Perhexiline 5.11 11
Perphenazine 6.00 1
Perphenazine 6.00 3
Phenobarbital 2.52 3
Phenobarbital 2.52 5
Phenobarbital 2.52 8
Phenobarbital 2.52 6
Phenytoin 3.62 3
Phenytoin 3.62 5
Phenytoin 3.62 8
Phenytoin 3.62 6
Pilsicainide 4.69 3
Pilsicainide 4.70 5
Pilsicainide 4.69 8
Pimozide 7.75 7
Pimozide 7.74 1
Pimozide 7.74 1
Pimozide 7.74 3
Pimozide 7.74 1
Pimozide 9.00 8
Pimozide 8.00 1
Pimozide 7.92 1
Pimozide 7.74 11
Pimozide 7.30 10
Pimozide 7.26 1
Pimozide 7.26 3
Pimozide 7.26 6
Pimozide 7.26 5
Prazosin 5.81 5
21
Prazosin 5.80 7
Prazosin 5.80 8
Prazosin 5.80 3
Prenylamine 6.23 3
Procainamide 3.86 8
Procainamide 3.86 6
Procainamide 3.86 3
Propafenone 6.36 5
Propafenone 6.36 7
Propafenone 6.36 1
Propafenone 6.36 6
Propafenone 5.70 1
Propafenone 6.36 3
Propafenone 5.70 3
Protriptyline 5.93 27
Prucalopride 5.22 6
Prucalopride 5.39 28
Prulifloxacin 3.46 1
Pyrilamine 5.22 3
Quetiapine 5.24 5
Quetiapine 5.24 7
Quetiapine 5.24 3
Quinidine 6.39 6
Quinidine 6.39 1
Quinidine 6.12 1
Renzapride 5.70 6
Risperidone 6.82 10
Risperidone 6.78 1
Risperidone 6.78 3
22
Risperidone 6.58 1
Risperidone 7.00 1
Risperidone 6.83 7
Risperidone 6.83 1
Risperidone 6.83 3
Risperidone 6.83 6
Risperidone 6.83 5
Risperidone 6.79 8
Risperidone 6.42 1
Risperidone 6.40 1
Ritonavir 5.09 1
Roxithromycin 4.44 1
Saquinavir 4.82 1
Saquinavir 4.82 1
Saxitoxin 6.52 6
Saxitoxin 5.25 6
Sertindole 8.57 1
Sertindole 8.52 7
Sertindole 8.52 1
Sertindole 7.19 1
Sertindole 8.57 3
Sertindole 8.52 3
Sertindole 8.30 1
Sertindole 8.00 10
Sertindole 7.90 8
Sertindole 7.85 11
Sertindole 7.83 1
Sertindole 7.83 5
Sertindole 7.82 6
23
Sertindole 6.68 1
Sertindole 7.85 3
Sertindole 7.83 3
Sertindole 6.68 3
Sildenafil 5.52 6
Sildenafil 5.48 1
Sildenafil 5.48 3
Sildenafil 5.48 7
Sildenafil 4.48 1
Sildenafil 4.48 3
Sildenafil 4.02 1
Sildenafil 4.00 11
Sildenafil 4.00 8
Sildenafil 4.00 6
Sildenafil 5.48 5
Sophocarpine 3.70 29
Sotalol 3.57 15
Sparfloxacin 4.74 1
Sparfloxacin 4.60 1
Spironolactone 4.64 1
Spironolactone 4.64 7
sulfamethoxazole 2.00 5
Tadalafil 4.00 1
Tamsulosin 3.98 7
Telithromycin 4.34 1
Telithromycin 4.25 1
Telithromycin 4.25 1
Terazosin 4.76 5
Terazosin 4.75 7
24
Terazosin 4.75 8
Terazosin 4.75 3
Terfenadine 7.25 7
Terfenadine 7.25 1
Terfenadine 7.25 3
Terfenadine 8.08 8
Terfenadine 8.06 1
Terfenadine 8.03 1
Terfenadine 7.96 1
Terfenadine 7.80 1
Terfenadine 7.80 1
Terfenadine 7.42 1
Terfenadine 7.28 1
Terfenadine 7.25 1
Terfenadine 7.25 1
Terfenadine 6.89 11
Terfenadine 6.70 10
Terfenadine 6.69 7
Terfenadine 6.67 1
Terfenadine 6.67 6
Terfenadine 6.67 5
Terfenadine 7.25 3
Terfenadine 6.69 3
Terfenadine 6.67 3
Thioridazine 6.72 1
Thioridazine 6.65 1
Thioridazine 5.97 1
Thioridazine 6.72 3
Thioridazine 6.65 3
25
Thioridazine 5.97 3
Thioridazine 7.48 6
Thioridazine 7.48 5
Thioridazine 7.48 7
Thioridazine 7.48 1
Thioridazine 7.45 11
Thioridazine 7.02 8
Thioridazine 6.41 1
Thioridazine 7.48 3
Thioridazine 6.41 3
Trazodone 6.16 3
Trazodone 5.54 3
Trazodone 6.16 30
Trazodone 5.54 31
Trazodone 5.54 5
Trazodone 5.54 8
Trifluoperazine 5.85 3
Trifluoperazine 5.04 5
Trimetoprim 3.62 5
Trimetoprim 3.62 10
Ulifloxacin 3.46 1
Vardenafil 4.92 1
Vardenafil 4.90 5
Vardenafil 4.89 3
Vardenafil 4.89 8
Verapamil 6.84 1
Verapamil 6.08 1
Verapamil 7.03 7
Verapamil 7.03 1
26
Verapamil 6.87 8
Verapamil 6.85 10
Verapamil 6.84 1
Verapamil 6.84 11
Verapamil 6.84 5
Verapamil 6.67 6
Verapamil 6.39 1
Verapamil 6.27 1
Verapamil 6.15 1
Verapamil 6.67 3
Verapamil 6.84 3
Vesnarinone 6.00 6
Vesnarinone 5.98 7
Vesnarinone 5.97 1
Vesnarinone 5.97 3
Vesnarinone 5.96 8
Vesnarinone 5.96 5
Vinpocetine 6.89 32
Ziprasidone 6.77 3
Ziprasidone 6.90 6
Ziprasidone 6.90 7
Ziprasidone 6.90 5
Ziprasidone 6.90 8
Ziprasidone 6.90 3
1. Prous Integrity Database, Copyright 1995-2008, Prous Science, http://www.prous.com (accessed
October 15th, 2008).
27
2. Dinges, J.; Albert, D. H.; Arnold, L. D.; Ashworth, K. L.; Akritopoulou-Zanze, I.; Bousquet, P.
F.; Bouska, J. L.; Cunha, G. A.; Davidsen, S. K.; Diaz, G. J.; Djuric, S. W.; Gasiecki, A. F.;
Gintant, G. A.; Gracias, V. J.; Harris, C. M.; Houseman, K. A.; Hutchins, C. W.; Johnson, E. F.;
Li, H.;.Marcotte, P. A.; Martin, R. L.; Michaelides, M. R.; Nyein, M.; Sowin, T. J.; Su, Z.;
Tapang, P. H.; Xia, Z.; Zhang, H. Q. 1,4-Dihydroindeno[1,2-c]pyrazoles with acetylenic side
chains as novel and potent multitargeted receptor tyrosine kinase inhibitors with low affinity for
the hERG ion channel. J. Med. Chem. 2007, 50, 2011-2029.
3. Kramer, C.; Beck, B.; Kriegl, J. M.; Clark, T. A composite model for hERG blockade.
ChemMedChem 2008 3, 254-265.
4. Slee, D. H.; Moorjani, M.; Zhang, X.; Lin, E.; Lanier, M. C.; Chen, Y.; Rueter, J. K.; Lechner,
S. M.; Markison, S.; Malany, S.; Joswig, T.; Santos, M.; Gross, R. S.; Williams, J. P.; Castro-
Palomino, J. C.; Crespo, M. I.; Prat, M.; Gual, S.; Díaz, J.-L.; Jalali,K.; Sai, Y.; Zuo, Z.; Yang,
C.; Wen, J.; O’Brien, Z.; Petroski, R.; Saunders, J. 2-Amino-N-pyrimidin-4-ylacetamides as A2A
receptor antagonists: 2. Reduction of hERG activity, observed species selectivity, and
structure−activity relationships. J. Med. Chem. 2008, 51, 1730–1739.
5. Ekins, S.; Balakin, K. V.; Savchuk,N.; Ivanenkov, Y. Insights for human ether-a-go-go-related
gene potassium channel inhibition using recursive partitioning and Kohonen and Sammon
mapping techniques. J. Med. Chem. 2006, 49, 5059-5071.
6. Briggs, K. A. Vitic - A data source for (quantitative) structure–activity relationship modeling.
Toxicology, 2007, 231, 113-114.
7. Yoshida, K.; Niwa, T. Quantitative structure-activity relationship studies on inhibition of hERG
potassium channels. J. Chem. Inf. Model. 2006, 46, 1371-1378.
8. Song, M.; Clark, M. Development and Evaluation of an in Silico Model for hERG Binding. J.
Chem. Inf. Model. 2006, 46, 392-400.
28
9. Meyers, K. M.; Méndez-Andino, J. L.; Colsona, A.-O.; Warshakoona, N. C.; Wosa, J. O.;
Mitchella, M. C,; Hodgea, K. M.; Howarda, J. M.; Ackleya, D. C.; Holberta, J. K.; Mittelstadta,
S. W.; Dowtya, M. E.; Obringera, C. M.; Reizes, O.; Hu, X. E. Aminomethyl
tetrahydronaphthalene ketopiperazine MCH-R1 antagonists - Increasing selectivity over hERG.
Bioorg. Med. Chem. Lett. 2007, 17, 819-822.
10. Keseru, G. M. Prediction of hERG potassium channel affinity by traditional and hologram
QSAR methods. Bioorg. Med. Chem. Lett. 2003, 13, 2773-2775.
11. Cavalli, A.; Poluzzi, E.; De Ponti, F.; Recanatini, M. Toward a pharmacophore for drugs
inducing the long QT syndrome: Insights from a CoMFA Study of hERG K+ channel blockers. J.
Med. Chem. 2002, 45, 3844-3853.
12. Siebrands, C. C.; Friederich, P. Inhibition of hERG channels by the local anaesthetic articaine.
Eur. J. Anaesthesiol. 2007, 24, 148-153.
13. Tanga, Q.; Jinc, M.-W.; Xiangc, J.-Z.; Donga, M..-Q.; Suna, H.-Y.; Laua. C.-P.; Li, G.-R. The
membrane permeable calcium chelator BAPTA-AM directly blocks human ether a-go-go-related
gene potassium channels stably expressed in HEK 293 cells. Biochem. Pharmacol. 2007, 74,
1596-1607.
14. Silvestre, J. S.; Prous. J. R. Comparative evaluation of hERG potassium channel blockade by
antipsychotics. Methods. Find. Exp. Clin. Pharmacol. 2007, 29, 457-465.
15. Thai, K.-M.; Ecker, G. F. A binary QSAR model for classification of hERG potassium channel
blockers. Biorg. Med. Chem. 2008, 16, 4107-4119.
16. Park, S. J.; Kim, K. S.; Kim, E. J. Blockade of hERG K+ channel by an antihistamine drug
brompheniramine requires the channel binding within the S6 residue Y652 and F656. J. Appl.
Toxicol. 2008, 28,104-111.
29
17. Danielsson, B. R.; Lansdell, K.; Patmore, L.; Tomson, T. Phenytoin and phenobarbital inhibit
human hERG potassium channels. Epilepsy Res. 2003, 55, 147-157.
18. Bains, W.; Basman, A.; White, C. hERG binding specificity and binding site structure: evidence
from a fragment-based evolutionary computing SAR study. Prog. Biophys. Mol. Biol. 2004, 86,
205-233.
19. Toga, T.; Kohmura, Y.; Kawatsu, R. The 5-HT4 Agonists Cisapride, Mosapride, and CJ-033466,
a novel potent compound, exhibit different human ether-a-go-go-related gene (hERG)-blocking
activities. J. Pharmacol. Sci. 2007, 105, 207-210.
20. Kim, K. S.; Shin, W.-H.; Park, S.-J.; Kim, E.-J. Effect of Clebopride, antidopaminergic
gastrointestinal prokinetics, on cardiac repolarization. Int. J. Toxicol. 2007, 26, 25-31.
21. Ridley, J. M.; Milnes, J. T.; Hancox, J. C.; Witchel, H. J. Clemastine, a conventional
antihistamine, is a high potency inhibitor of the hERG K+ channel. J. Mol. Cel. Cardiol. 2006,
40, 107-118.
22. Duncan, R. S.; McPate, M. J.; Ridley, J. M.; Gaoa, Z.; James, A. F.; Leishman, D. J.; Leaney, J.
L.; Witchel, H. J.; Hancox, J. C. Inhibition of the hERG potassium channel by the tricyclic
antidepressant doxepin. Biochem. Pharmacol. 2007, 74, 425-437.
23. Kelemen, K.; Kiesecker, C.; Zitron, E.; Bauer, A.; Scholz, E.; Bloehs, R.; Thomas, D.; Greten,
J.; Remppis, A.; Schoels, W.; Katus. H. A.; Karle, C. A. Green tea flavonoid epigallocatechin-3-
gallate (EGCG) inhibits cardiac hERG potassium channels. Biochem. Biophys. Res. Commun.
2007, 364, 429-435.
24. Zünkler, B. J.; Claaßen, S.; Wos-Magangaa, M.; Rustenbeck, I.; Holzgrabe, U. Effects of
fluoroquinolones on hERG channels and on pancreatic β-cell ATP-sensitive K+ channels.
Toxicology 2006, 228, 239-248.
30
25. Kang, J.; Chen, X. L.; Wang, H.; Rampe, D. Interactions of the narcotic l-α-acetylmethadol with
human cardiac K+ channels. Europ. J. Pharmacol. 2003, 458, 25-29.
26. Scholz, E. P.; Konrad, F. M.; Weiss, D. L.; Zitron, E.; Kiesecker, C.; Bloehs, R.; Kulzer, M.;
Thomas, D.; Kathöfer, S.; Bauer, A.; Maurer, M. H.; Seemann, G.; Katus, H. A.; Karle. C. A.
Anticholinergic antiparkinson drug orphenadrine inhibits hERG channels: block attenuation by
mutations of the pore residues Y652 or F656. Naunyn Schmiedebergs Arch. Pharmacol. 2007,
376, 275-284.
27. Jo, S. H.; Hong, H. K.; Chong, S. H.; Choe, H. Protriptyline block of the human ether-à-go-go-
related gene (hERG) K+ channel. Life Sci. 2008, 82, 331-340.
28. Chapman, H.; Pasternack, M. The action of the novel gastrointestinal prokinetic prucalopride on
the hERG K+ channel and the common T897 polymorph. Europ. J. Pharmacol. 2007, 554, 98-
105.
29. Zhao, X.-L.; Qi, Z.-P.; Fang, C.; Chen, M.-H.; Lu, Y.-J.; Li, B.-X.; Yang. B.-F. hERG K+
channel blockade by novel antiviral drug sophocarpine, Biol. Pharm. Bull. 2008, 31, 627-632.
30. Tarantino, P.; Appleton, N.; Lansdell, K. Effect of trazodone on hERG channel current and QT-
interval. Europ. J. Pharmacol. 2005, 510, 75-85.
31. Zitron, E.; Kiesecker, C.; Scholz, E.; Lück, S.; Bloehs, R.; Kathöfer, S.; Thomas, D.; Kiehn, J.;
Kreye, V. A. W.; Katus, H. A.; Schoels, W.; Karle, C. A. Inhibition of cardiac hERG potassium
channels by the atypical antidepressant trazodone. Naunyn Schmiedebergs Arch. Pharmacol.
2004, 370,146-156.
32. Yunomae, K.; Ichisaki, S.; Matsuo, J.; Nagayama, S.; Fukuzaki, K.; Nagata, R.; Kito, G. Effects
of phosphodiesterase (PDE) inhibitors on human ether-a-go-go related gene (hERG) channel
activity. J. Appl. Toxicol. 2007, 27, 78-85.