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. 2021 Apr 5;12(5):726–731. doi: 10.1021/acsmedchemlett.0c00654

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
a

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.