Table 4.
Comparison of PARP1 selective inhibitors and selected first-generation PARP inhibitors
| Drugs | Olaparib | Talazoparib | NMS03305293 | AZD5305 | AZD9547 |
|---|---|---|---|---|---|
| PARP1 IC50 (μM)a | 0.007 | 0.009 | <0.01 | 0.003 | <0.005 |
| PARP2 IC50 (μM)a | 0.006 | 0.030 | 0.691 | >1.4 | >93 |
| PARP1/2 selectivity fold | 1 | 3 | >200 | >460 | 19107 |
| PARP3/5a/6 IC50 (μM)a | 0.2/70/1.8 | 0.2/1.9.1.1 | 0.5/>10/not reported | 3.4/ > 89/26 | All > 100 |
| PARP1 trappingb | + | ++ | - | ++ | Yes |
| PARP2 trappingb | + | ++ | - | - | - |
| DLD1 BRCA2−/− cell line antiprolifertive GI50 (nM) | 11 | 0.5 | Not reported | 0.4 | 1.4 |
| Pgp substrate | Yes | Yes | No | Yes | No |
| CNS penetration | Limited, Rat/Monkey Kpuu: <0.03/<0.1 | Limited, Rat Kpuu: <0.03 | Yes, with a brain/plasma ratio of 4-10 in rats and mouse | Limited, Rat/Monkey Kpuu: <0.05/<0.01 | Yes, with Rat Kpuu 0.31 |
aDetermined by a fluorescence polarization assay
bDetermined by an immunofluorescence–based assay