Table 5.
Effect of the expression of nucleoside transporters on the sensitivity of tubercidin analogs.
| Compound | 3′ | 6-Subst | 7-Subst | LmexCas9 | SUPKO | SUPKO+TcoAT1 | SUPKO+TvxNT3 | |||
|---|---|---|---|---|---|---|---|---|---|---|
| EC50 (µM) | EC50 (µM) | RF (Cas9) | EC50 (µM) | RF (SUPKO) | EC50 (µM) | RF (SUPKO) | ||||
| Tubercidin | OH | NH2 | 0.44 ± 0.06 | >100 | >230 | >100 | - | >100 | - | |
| Cordycepin | NH2 | 91.6 ± 12.9 | >100 | >1.09 | >100 | - | >100 | - | ||
| FH7429_u | NH2 | Br | 27.3 ± 7.0 | >200 | >3.6 | 27.0 ± 5.8 | >7.4 | 42.9 ± 12.0 | >2.33 | |
| FH7429_d | NH2 | 15.1 ± 1.7 | >100 | >6.63 | 65.3 ± 7.6 | >1.53 | >100 | - | ||
| FH6367 | OH | NH2 | CF3 | 26.1 ± 6.4 | >100 | >3.83 | 3.79 ± 0.34 | >26.4 | 7.4 ± 1.4 | >13.5 |
| FH3169 | OH | NH2 | Cl | 0.23 ± 0.005 | 15.4 ± 2.7 | 67.7 | 9.41 ± 0.56 | 1.64 | 15.9 ± 2.5 | 0.97 |
| TH1008 | OH | NH2 | Pyridin-2-yl | 11.7 ± 0.5 | >100 | >8.5 | >100 | - | >100 | - |
| TH1003 | OH | NH2 | Br | 2.43 ± 0.14 | >100 | >41.2 | 71.1 ± 5.0 | >1.4 | >100 | - |
| FH3167 | OH | NH2 | F | 0.096 ± 0.009 | 63.4 ± 5.5 | 660 | 7.5 ± 0.9 | 8.48 | 57.2 ± 6.8 | 1.1 |
| CL4510 | OH | OCH3 | 0.39 ± 0.05 | 2.28 ± 0.21 | 5.84 | 2.2 ± 0.03 | 1.03 | 2.05 ± 0.04 | 1.1 | |
| FH8517 | NH2 | F | 3.09 ± 0.04 | 9.96 ± 2.04 | 3.22 | 6.1 ± 0.7 | 1.64 | 9.42 ± 1.41 | 1.06 | |
| FH8505 | NH2 | ethynyl | 92.7 ± 4.3 | >100 | >1.08 | 89.9 ± 12.5 | >1.1 | 80.0 ± 7.7 | >1.25 | |
| FH8496 | NH2 | I | 51.8 ± 10.3 | 52.6 ± 0.0 | 1.01 | 23.9 ± 5.6 | >2.2 | 40.0 ± 9.2 | >1.2 | |
| FH9531 | OH | O-iPr | Cl | >100 | >100 | - | >100 | - | >100 | - |
| FH10659 | NH2 | -vinyl | >100 | >100 | - | >100 | - | >100 | - | |
| Pentamidine | 1.43 ± 0.05 | 1.83 ± 0.29 | 1.28 | 1.73 ± 0.20 | 1.1 | 2.31 ± 0.18 | 0.77 | |||
EC50 values were obtained using the resazurin-based assay in 96-well plates, with doubling dilutions over 1 or 2 rows (11 or 23 dilutions) as necessary to obtain a full EC50. Data listed are the average of 3 or more experiments and SEM. When inhibition was less than 50% at 100 µM the value is listed as >100. RF is the Resistance Factor relative to the cell line given in brackets, e.g., RF(cas9) = EC50(SUPKO)/EC50(Cas9).