Table S2. Reported hERG inhibitors were validated by automated patch clamp-IonWorks QuattroTM
No.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
Compound name
Ajmaline
Apomorphine
Astemizole
Atomoxetine
Bepridil
Benperidol
Buspirone
Carvedilol
Cetirizine
(±)-Chlorpheniramine
maleate
Chlorpheniramine
Chlorpromazine
Cisapride
Citalopram
Clofilium tosylate
Clomipramine
Clotrimazole
Clozapine
Cocaine
Desipramine
Diazepam
23760133
11957529
2247
54840
50088
16363
36431
2585
1549000
5281068
56463108
46500370
855746
49681605
56322751
56463215
11533010
49681735
49681558
49681628
1μM
(%)
-33.4
-24.6
-103.4
-29.7
-55.4
-101.1
-30.8
-35.0
-8.5
-11.4
5281068
6240
5311047
146571
175533
68539
2812
2818
517282
65327
1688
56422503
56422870
56463519
49681820
56463363
855785
11532882
56422144
24824088
26732610
855615
-25.8
-14.8
-104.6
-25.3
-105.2
-15.2
-10.9
-8.4
-23.8
-10.0
-21.2
CID
SID
10μM
(%)
-73.8
-88.8
-106.2
-66.6
-102.7
-103.0
-65.9
-95.6
-26.2
-57.2
IC50(μM )
5.47
3.11
0.05
8.19
1.04
0.17
6.25
1.14
37.20
9.77
log10(IC50)
-5.3
-5.5
-7.3
-5.1
-6.0
-5.2
-5.9
-4.4
-5.0
Reported
IC50(μM)
1.00
2.40
0.02
6.30
0.55
0.004
3.98
10.4
30.2
19.0
-61.1
-72.2
-106.7
-79.9
-106.7
-58.3
-40.4
-40.3
-55.9
-32.7
-63.8
8.13
5.15
0.02
3.73
0.02
9.04
18.77
19.63
16.70
28.05
7.40
-5.1
-5.3
-7.7
-5.4
-7.7
-5.0
-4.7
-4.7
-4.8
-4.6
-5.1
19.0
1.56
0.018
3.97
0.15
3.98
3.60
2.50
7.24
28.5
31.6
-6.8
LOG10
(Reported IC50)
-6.0
-5.6
-7.6
-5.2
-6.3
-8.4
-5.4
-4.9
-4.5
-4.7
References
-4.7
-5.8
-7.7
-5.4
-6.8
-5.4
-5.4
-5.6
-5.1
-4.6
-4.5
[12, 13]
[6]
[7]
[1]
[8]
[2]
[9]
[10]
[11]
[11]
[12, 13]
[14]
[3]
[15]
[16]
[10]
[17]
[18]
[19]
[20]
[10]
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
Diphenhydramine
Dofetilide
Donepezil
Doxazosin mesylate
Droperidol
Duloxetine
Flecainide
Flunarizine
Fluoxetine
Fluphenazine
Fluspirilene
Granisetron
Haloperidol
Haloperidol
hydrochloride
Hydroxyzine
Imipramine
Ketanserin
Ketoconazole
Lidoflazine
Loratadine
Mexiletene
Mesoridazine besylate
Mibefradil
Nefazodone
hydrochloride
8980
71329
5741
62978
3168
60835
41022
6365505
62857
56422455
49681772
49732006
56422468
855921
49681583
855927
56320643
56422172
11532937
49731982
56422397
49681790
-22.6
-105.7
-74.6
-21.1
-95.5
-17.65
-50.1
-16.8
-41.3
-12.08
-56.5
-17.0
-98.6
-97.9
-48.8
-106.0
-96.1
-68.9
-103.1
-67.79
-79.4
-39.2
-86.2
-72.45
-105.8
-37.6
-104.3
-105.7
11.43
0.03
0.70
6.01
0.20
7.71
2.57
10.28
2.75
5.09
0.95
21.28
0.11
0.08
-4.9
-7.5
-6.2
-5.2
-6.7
-5.1
-5.6
4.9
-5.6
-5.3
-6.0
-4.7
-6.9
-7.1
18.5
0.01
1.3
18.2
0.03
25.0
3.91
1.95
1.50
0.10
2.34
3.73
0.17
0.17
-4.7
-8
-5.9
-4.7
-7.5
-4.6
-5.4
-5.7
-5.8
-7.0
-5.6
-5.4
-6.8
-6.8
56422208
6602611
3396
6918003
3559
11495267
71612
8228
135348
456201
3926
3957
21467
36207
16746591
54911
855928
56422890
56422778
56422892
56463026
56424146
26732616
49681702
26732644
49681554
-54.3
-37.8
-29.9
-20.5
-93.2
-12.8
-60.45
-45.7
-30.0
-33.5
-93.5
-75.4
-81.8
-72.0
-113.6
-43.6
-107.97
-86.0
-99.4
-95.0
1.14
5.06
3.15
5.95
0.18
17.32
1.01
1.90
0.73
1.23
-5.9
-5.3
-5.5
-5.2
-6.8
-4.8
-6.0
-5.7
-6.1
-5.9
0.62
3.40
0.11
1.7
0.02
4.00
3.70
0.55
1.43
0.045
-6.2
-5.5
-7.0
-5.8
-7.8
-5.4
-5.4
-6.3
-5.8
-6.6
[11]
[21]
[22]
[23]
[24]
[25]
[26]
[1]
[15]
[27]
[11]
[11]
[3]
[3]
[28]
[29]
[30]
[11]
[31]
[13]
[32]
[33]
[2]
[34]
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
Nefazodone
Nifekalant
hydrochloride
Olanzapine
Ondansetron
Orphenadrine
Pergolide
Perhexiline
Perhexiline
Perphenazine
Pimozide
Prazocin
Prochlorperazine
Propafenone
Pyrilamine
Quetiapine fumarate
Quetiapine
Quinidine
Risperidone
Saquinavir
Sertraline
Sildenafil
Spironolactone
Tamoxifen
Terazosin
Terfenadine
4449
122188
49666410
49681608
-35.4
-48.8
-93.2
-92.5
2.01
1.80
-5.7
-5.7
0.045
7.90
-6.6
-5.1
[34]
4585
68647
83823
47812
5284439
5284439
4748
16362
68546
4917
36708
5284451
6918224
5002
441074
5073
60934
68617
5212
5833
2733525
44383
5405
49666419
49681594
11532864
11533039
56422147
855892
56422427
56422165
56462999
855827
855997
56422415
49681551
49666758
56320931
49666400
49681831
49665783
50085897
47193741
49816809
861987
56422373
-27.8
-26.2
-19.7
-27.9
-11.6
-2.8
-12.3
-96.9
-25.6
-24.4
-76.7
-41.7
-13.6
-18.0
-40.8
-57.6
-33.02
-9.0
-12.5
-1.6
-7.2
-8.8
-40.3
-43.2
-58.4
-74.4
-65.3
-52.6
-46.6
-79.3
-107.6
-65.9
-83.1
-103.2
-71.4
-44.6
-37.9
-98.1
-98.0
-102.09
-43.9
-39.7
-39.5
-64.3
-28.4
-108.4
21.00
12.14
4.99
9.41
12.64
11.79
4.13
0.11
6.55
3.73
0.43
4.95
21.00
21.87
1.59
0.93
0.54
16.14
19.32
19.50
7.12
32.81
1.45
-4.7
-4.9
-5.3
-5.0
-4.9
-4.9
-5.4
-7.0
-5.2
-5.4
-6.4
-5.3
-4.7
-4.7
-5.8
-6.0
-6.3
-4.8
-4.7
-4.7
-5.1
-4.5
-5.8
6.01
0.81
0.85
0.12
7.80
7.80
1.00
0.02
1.57
22.6
2.00
6.00
5.77
5.77
2.5
0.17
15.3
0.7
100
23.01
45.30
17.70
0.43
-5.2
-6.1
-6.1
-6.9
-5.1
-5.1
-6.0
-7.7
-5.8
-4.7
-5.7
-5.2
-5.2
-5.2
-5.6
-6.8
-4.8
-6.1
-4.0
-4.6
-4.3
-4.8
-6.4
[36]
[35]
[37]
[38]
[7]
[39]
[39]
[14]
[40]
[23]
[41]
[13]
[13]
[36]
[36]
[4]
[36]
[42]
[43]
[11]
[11]
[11]
[11]
[5]
71
72
73
74
Thioridazine
Trifluoperazine
Verapamil
Vinpocetine
66062
2913535
62969
443955
855568
56424129
856000
855619
-18.7
-12.2
-73.9
-115.8
-87.2
-60.4
-96.7
-121.8
4.05
8.65
0.70
0.05
-5.4
-5.1
-6.2
-7.3
0.22
1.41
0.83
0.13
-6.7
-5.9
-6.1
-6.9
[14]
[14]
[2]
[44]
Note: CID: compound ID; SID: Substance ID.
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antianginal agent perhexiline maleate. British journal of pharmacology 1999; 127 (1): 243-51.
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392 (3): 137-40.
41 Kim MD, Eun SY, Jo SH. Blockade of HERG human K+ channel and IKr of guinea pig cardiomyocytes by prochlorperazine . European journal of pharmacology 2006;
544 (1-3): 82-90.
42 Anson BD, Weaver JG, Ackerman MJ, Akinsete O, Henry K, January CT, et al. Blockade of HERG channels by HIV protease inhibitors. Lancet 2005; 365 (9460):
682-6.
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44 Yunomae K, Ichisaki S, Matsuo J, Nagayama S, Fukuzaki K, Nagata R, et al. Effects of phosphodiesterase (PDE) inhibitors on human ether-a-go-go related gene
(hERG) channel activity. Journal of applied toxicology : JAT 2007; 27 (1): 78-85.