Table 1 Data for PROTACs 4 and 6 and control PROTACs 5 and 7 showing biochemical potency, DC50, MDP challenge assay potency as well as rat intravenous PK parameters.
From: Extended pharmacodynamic responses observed upon PROTAC-mediated degradation of RIPK2
Cpnd | RIPK2 FP pIC50 ± SEM (n) | hPBMC pDC50 /Dmax ± SEM, 24 h (n = 3) | hPBMC MDP pIC50 ± SEM, 6 h (n = 3) | hWB MDP pIC50 ± SEM (n) | rWB MDP pIC50 ± SEM (n) | Rat Clearance mL/min/kg | Rat Vdss L/kg | Rat T½ h |
|---|---|---|---|---|---|---|---|---|
4 | 6.6 ± 0.02 (8) | 7.9 ± 0.2/69.2 ± 11.5% | 8.0 ± 0.5 | 7.7 ± 0.05 (4) | 7.7 ± 0.16 (4) | 18 | 11 | 6.9 |
5 | 6.7 ± 0.05 (12) | Non-degrader | 6.5 ± 0.5 | – | – | – | – | – |
6 | 8.0 ± 0.05 (24) | 9.4 ± 0.2/94.3 ± 3.2% | 9.3 ± 0.03 | 8.5 ± 0.07 (14) | 8.5 ± 0.1 (4) | 10 | 7.6 | 16 |
7 | 8.4 ± 0.09 (4) | Non-degrader | 7.8 ± 0.2 | – | – | – | – | – |
