Table 1.
IC50, solubility and microsomal stability of PHGDH inhibitors. IC50s are averages±standard deviations and the number of replicates is provided in the table. Compound solubility was determined in assay buffer containing 0.05% BSA (kinetic solubility) and in PBS pH 7.4 (aqueous solubility). IC50s were measured in assay buffer.
| PHGDH IC50 (µM) |
Kinetic Solubility in Assay Buffer (µM) |
Aqueous Solubility (µM) |
Rat Microsome Stability (t1/2, min.) |
|
|---|---|---|---|---|
| PHGDH-Hit (1) | 15.3 | - | 19 | 24 |
| NCT-502 (2) | 3.7±1.0 (n=8) | 662.2±39.8 (n=3) | 1.2±1.2 (n=8) | >30 (n=10) |
| NCT-503 (3) | 2.5±0.6 (n=4) | 61.5±2.0 (n=3) | 25.3±2.6 (n=8) | >30 (n=8) |
| PHGDH-Inactive (4) | >57 (n=4) | 251.4±24.9 (n=3) | >148 (n=2) | >30 (n=2) |