Table 1.
Compound | SPR KD (µM) of Nsp14 | IC50 (µM)a | |||||
---|---|---|---|---|---|---|---|
Nsp 14 | G9a | BCDIN3D | ALKBH5 | SETD3 | METTL3-14 | ||
SS148 | 0.05 | 0.07 ± 0.006 | NI | 0.03 ± 0.002 | NI | NI | 0.9 |
WZ16 | NA | 0.19 ± 0.04 | NI | 1.7 | NI | 3.4 | 3.4 |
DS0464 | 1.6 | 1.1 ± 0.2 | NI | 46 ± 9 | NI | NI | NI |
DS0466 | 2.4 | 3.4 ± 1.4 | NI | >50 | NI | NI | NI |
JL27-56A1 | 0.2 | 0.26 ± 0.13 | NI | 19 | NI | 23 | 10 |
Compound 8 | 18.9 | 95 ± 6 | NI | NI | NI | NI | NI |
SAH | 0.14 | 0.13 ± 0.03 | NA | NA | NA | NA | NA |
MTTR025495 | 6.2 | 17 ± 2 | NA | NA | NA | NA | NA |
The screening hits were tested for binding to nsp14 by SPR and for inhibition of MTase activity of nsp14 and selected MTases by activity assays. All values are from experiments presented in Figure 3andSupplemental Figures S7, S10, S11, S12, S13, and S14. NA, not assessed; NI, no inhibition. aIC50 values are presented as the mean ± standard deviation (n = 3).