Table 2. IC50, Ligand Efficiency, and Alpha Ki Values of Fragment Hits and Compound 1 (7759844) against Mth IMPDH ΔCBS.
| Compd | IC50 (μM) (LE)a | IMP αKi (μM) | NAD αKi (μM) |
|---|---|---|---|
| 1 | 0.77 ± 0.06 (0.40) | 0.86 ± 0.03 (UC)b | 0.55 ± 0.02 (UC) |
| 2 | 674 ± 53 (0.36) | 609 ± 3 (UC) | 512 ± 23 (UC) |
| 11 | 336 ± 6 (0.39) | 361 ± 53 (UC) | 310 ± 30 (UC) |
| 14 | 400 ± 7 (0.42) | 238 ± 6 (Mixed) | 262 ± 39 (UC) |
| 16 | 433 ± 60 (0.31) | 398 ± 81 (Mixed) | 525 ± 64 (UC) |
| 18 | 512 ± 37 (0.37) | 554 ± 70 (UC) | 452 ± 26 (UC) |
| 19 | 325 ± 9 (0.37) | 126 ± 34 (Mixed) | 355 ± 47 (UC) |
a
Ligand efficiency was calculated using the equation LE = (1.37 × pIC50)/HA, where HA means heavy atom, i.e., a non-hydrogen atom.
b
UC: Uncompetitive inhibition.