Table 2.
Properties of analogs of compound 221.
| Compound | RNP assay | Viral Yield Reduction Assay | MST | SPR | |||
|---|---|---|---|---|---|---|---|
| IC50a (μM) | CC50b (μM) | IC50c (μM) | CC50d (μM) | Kde (μM) | Kdf (μM) | ||
| 221 | 68.8 ± 1.9 | >100 | 30.58 ± 21.37 | >100 | N.D. | N.D. | |
| Analogs obtained through chemical modification | S1b | 87.8 ± 21.8 | >100 | >100 | >100 | N.D. | N.D. |
| S2a | 9.69 ± 3.00 | 84.6 ± 17.30 | 7.74 ± 6.02 | >100 | 1.77 ± 0.78 | N.D. | |
| S2b | 14.2 ± 3.6 | >100 | 4.96 ± 3.84 | 42.8 ± 9.0 | 16.2 ± 8.3 | N.D. | |
| S2d | >12.5 | 66.6 ± 6.09 | 3.18 ± 2.44 | 35.6 ± 9.24 | >25 | N.D. | |
| S2e | 6.69 ± 7.49 | >100 | 5.11 ± 4.22 | 53.1 ± 9.25 | 50.9 ± 25.5 | N.D. | |
| S2f | 62.4 ± 22.4 | >100 | >100 | >100 | N.D. | N.D. | |
| Commercially available analogs | 310 | 98.45 ± 3.6 | >100 | >100 | >100 | N.D. | N.D. |
| 312 | 35.37 ± 4.3 | >100 | 27.0 ± 16.8 | >100 | 38.2 ± 5.5 | 37.7 ± 4.6 | |
| 384 | >100 | >100 | >100 | >100 | N.D. | N.D. | |
| 389 | 96.54 ± 28.7 | >100 | >100 | >100 | N.D. | N.D. | |
| 387 | 15.45 ± 2.8 | >100 | 6.45 ± 5.63 | >100 | 46.3 ± 27.4 | N.D. | |
| 392 | >6.25 | 62.66 ± 18.7 | 4.78 ± 5.63 | 87.03 ± 7.22 | 6.03 ± 1.05 | N.D. | |
aIC50 is the concentration of test compound which produces 50% inhibition of RNP activity compared with DMSO control; reported values represent means ± standard deviation of data from three independent experiments.
b293T cells were incubated with test compounds for 24 hrs; CC50 is the concentration of test compounds which produces 50% cytotoxicity as determined by MTT assays. Reported values represent means ± standard deviation of data from three independent experiments.
cIC50 is the concentration of test compound which produces 50% inhibition of viral yield compared with DMSO control; reported values represent means ± standard deviation of data from three independent experiments.
dMDCK cells were incubated with test compounds for 24 hrs; CC50 is the concentration of test compounds which produces 50% cytotoxicity as determined by MTT assays. Reported values represent means ± standard deviation of data from three independent experiments.
eKd were measured by MST and calculated by NanoTemper MO.Control using ‘Kd model’. Reported values represent Kd ± confidence level calculated by the software.
fKd were measured by SPR and calculated by Biacore BiaEvaluation v 4.1 using ‘1:1 Langmuir binding model’. Reported values represent mean ± standard deviation of data from three independent experiments.