IVIVC for human CSF Aβ
Free brain concentration was estimated from CSF concentration assuming that the free brain/CSF ratio in human is the same as in mouse. The results in 129/SVE mouse are included for ease of comparison with human.
| Compound | In Vitro Aβ42 IC50 | Projected Human Free Brain Concentration Causing 50% Inhibition of Generation of | PK/PD Modeling-Derived Free Brain Concentration in 129/SVE Mouse Causing 50% Inhibition of Generation of CSF Aβx-40 | |
|---|---|---|---|---|
| CSF Aβ1–40 | CSF Aβ1–42 | |||
| nM | ||||
| BMS-708163 | 0.34 | 17 | 12 | 21 |
| LY450139 | 3.3 | 339 | 550 | 192 |