Table 1.
Comparison of results of our FP competitive binding assay to reported anti-influenza activities of known endonuclease inhibitors. Reported FP values are the average of triplicate measurements ± standard error of the mean (SEM). ND = no data.
Compound | Structure | Reported IC50 (MM) | FP EC50 (MM) | FP Ki (MM) | BEIa | LEIb | |
---|---|---|---|---|---|---|---|
1 (DPBA) |
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R = H | 21.3c | 2.07 ± 0.03 | 0.48 ± 0.01 | 33.0 | 0.62 |
5 | R = Ph | 3.7c | 3.56 ± 0.07 | 0.96 ± 0.02 | 22.5 | 0.42 | |
6 | R = piperazine | ND | 1.5 ± 0.8 | 0.3 ± 0.3 | 23.7 | 0.45 | |
7 | R = methoxy | ND | 6.7 ± 0.1 | 1.97 ± 0.03 | 25.7 | 0.49 | |
8 | R = oxyphenyl | ND | 1.45 ± 0.07 | 0.28 ± 0.02 | 23.1 | 0.43 | |
9 | R = benzyloxy | ND | 6.8 ± 0.2 | 1.99 ± 0.06 | 19.1 | 0.30 | |
2 (L-742,001) |
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R = Ph | 0.430c | 0.86 ± 0.04 | 0.09 ± 0.01 | 17.0 | 0.34 |
10 | R = cyclohexane | 0.33c | 0.8 ± 0.2 | 0.084 ± 0.001 | 16.9 | 0.34 | |
3 |
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15.0d | 3.22 ± 0.04 | 0.85 ± 0.02 | 34.3 | 0.65 | |
11 |
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ND | 6.8 ± 0.5 | 2.0 ± 0.2 | 27.8 | 0.52 | |
12 |
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ND | 8.17 ± 0.02 | 2.440 ± 0.006 | 24.0 | 0.46 | |
13 |
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ND | >250 | ||||
14 |
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ND | >250 | ||||
15 |
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ND | >250 | ||||
16 |
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R = CH3 | >500c | >250 | |||
17 | R = tert-butyl | ND | >250 | ||||
18 |
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>500c | >250 | ||||
19 |
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>500c | >250 |
BEI = Binding efficiency index based on FP data (pKi,/MW), where MW is molecular weight in kDa (55).
LE = Ligand efficiency based on FP data (ΔG/N), where ΔG = -RTlnKi and N is the number of heavy atoms (56).
Published results in an influenza virus in vitro transcription assay (29).
Published results in an influenza virus in vitro transcription assay (53).