Table 1.
A Novel Series of Small Molecules Show Selectivity for Inhibition of CTPS1 Over CTPS2 That Is Species Dependent
| STP-A | STP-B | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Species | CTPS1 IC50 (µM) | SD | N | CTPS2 IC50 (µM) | SD | N | Fold selectivity (CTPS1/CTPS2) | CTPS1 IC50 (µM) | SD | N | CTPS2 IC50 (µM) | SD | N | Fold selectivity (CTPS1/CTPS2) |
| Human | 0.0148 | 0.004 | 10 | 1.87 | 0.376 | 10 | 126 | 0.0093 | 0.0038 | 12 | 12.62 | 5.24 | 12 | 1,357 |
| Dog | 0.0293 | 0.002 | 4 | 4.14 | 1.481 | 4 | 141 | 0.0259 | 0.0058 | 8 | 21.75 | 37.75 | 7 | 840 |
| Mouse | 0.0267 | 0.008 | 5 | 0.126 | 0.020 | 4 | 5 | 0.0095 | 0.0030 | 13 | 1.33 | 0.64 | 12 | 140 |
| Rat | 0.0233 | 0.002 | 4 | 0.023 | 0.002 | 4 | 1 | 0.0095 | 0.0029 | 12 | 0.47 | 0.33 | 12 | 49 |
The table shows data for 2 exemplar compounds, shown in Figure 1A, consisting of geometric mean relative IC50 values for the inhibition of enzymatic activity in a recombinant protein assay.
CTP synthase 1 is a novel therapeutic target in lymphoma; IC50 = half maximal inhibitory concentration; SD = standard deviation.