Table 2. Examination of the Reversibility of H3K27Ac Inhibition upon Treatment with A-485 or Compound 2a.
|
A-485 |
compound 2 |
|||
|---|---|---|---|---|
| washout (WO) | EC50 (μM) | fold shift EC50 | EC50 (μM) | fold shift EC50 |
| 0 h | 0.227 | N/A | 0.011 | N/A |
| 1 h WO | >10 | >44 | 0.015 | 1.3 |
| 2 h WO | >10 | >44 | 0.017 | 1.5 |
| 4 h WO | >10 | >44 | 0.024 | 2.1 |
| 8 h WO | >10 | >44 | 0.129 | 11.3 |
| 24 h WO | >10 | >44 | 0.544 | 47.8 |
| 48 h WO | >10 | >44 | 0.656 | 57.7 |
| 48 h no WO | 0.253 | 1.11 | 0.021 | 1.8 |
Inhibition of H3K27Ac is rapidly reversible in the case of A-485 but is significantly less reversible in the case of compound 2, pointing to the prolonged inhibition of the target by the drug. See Figures S2 and S3 for dose–response curves.