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. 2021 Feb 11;12(3):380–388. doi: 10.1021/acsmedchemlett.0c00532

Figure 4.

Figure 4

Oral bid dosing simulation (modeling a dose interval of 10 h), showing simulated total brain concentration of 12. a Estimates of final parameters from 10 mg/kg po were used to predict concentrations achieved following 3 mg/kg po. Both doses are predicted to provide brain exposure exceeding class IIa HDAC IC50 for ∼4–6 h post each dose and to have minimal effect on engaging class I/IIb HDACs, with brain exposure failing to reach concentrations > EC10 for class I/IIb substrate acetylation, as determined empirically (SI Figure 3B–C). *The in vivo class IIa IC50 (235 nM) was estimated from the measured cellular IC50 (40 nM) adjusted for 12 Fu of 0.17 in brain homogenate.