Table 1.
PHGDH Inhibition and Cell Proliferation Inhibition Results of Compounds 19–35
| compd | R | PHGDH inhibition (IC50, μM)a | cell proliferation inhibition
(IC50, μM)a
|
|||||||
|---|---|---|---|---|---|---|---|---|---|---|
| MDA-MB-231 | SiHa | HL-60 shCTRL | HL-60 shPHGDH | |||||||
|
|
|
|||||||||
| +Ser | −Ser | IC50+Ser/IC50−Ser | +Ser | −Ser | IC50+Ser/IC50−Ser | |||||
| 12 | 75.2 | >100 | >100 | 57.5 | >1.7 | >100 | 83 | >1.2 | >100 | |
| 8 | 16.0 | >100 | 19.1 | 5.6 | 3.4 | 24.3 | 7.0 | 3.5 | >100 | |
| 19 | H | 30.9 | >100 | 71.7 | 7.9 | 9,1 | >100 | 18.3 | >5.5 | >100 |
| 20 | 2-F | >200 | nd | nd | nd | nd | nd | nd | nd | nd |
| 21 | 3-F | >200 | nd | nd | nd | nd | nd | nd | nd | nd |
| 22 | 4-F | 68.9 | >100 | >100 | 43.3 | >2.3 | >100 | 64.4 | 1.5 | >100 |
| 23 | 2-Cl | >200 | >100 | >100 | >100 | >100 | >100 | >100 | ||
| 24 | 3-Cl | >200 | >100 | >100 | >100 | >100 | >100 | >100 | ||
| 25 | 4-Cl | 8.7 | >100 | 21.0 | 6.6 | 3.2 | 50.5 | 15.5 | 3.3 | >100 |
| 26 | 2-Br | 160.7 | nd | nd | nd | nd | nd | nd | nd | nd |
| 27 | 3-Br | >200 | nd | nd | nd | nd | nd | nd | nd | nd |
| 28 | 4-Br | 130.7 | >100 | 20.4 | 7.9 | 2.6 | 37.2 | 16.9 | 2.2 | >100 |
| 29 | 2-I | >200 | nd | nd | nd | nd | nd | nd | nd | nd |
| 30 | 3-I | >200 | nd | nd | nd | nd | nd | nd | nd | nd |
| 31 | 4-I | 177.7 | >100 | 25.7 | 9.3 | 2.8 | 19.6 | 7.1 | 2.8 | >100 |
| 32 | 2-NO2 | >200 | nd | nd | nd | nd | nd | nd | nd | nd |
| 33 | 3-NO2 | 88.1 | nd | nd | nd | nd | nd | nd | nd | nd |
| 34 | 4-NO2 | 35.1 | >100 | 22.8 | 7.6 | 3 | 17.6 | 6.0 | 2.9 | >100 |
| 35 | 4-Ph | >200 | nd | nd | nd | nd | nd | nd | nd | nd |
a
All experiments to determine IC50 values were performed with at least triplicates at each compound dilution, and all IC50 values were averaged when determined in two or more independent experiments. nd = not determined.