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Figure 1. PK analysis of CPT and in vivo efficacy of CPT in the APP(swe)/PS1(deltaE9) 2xTg mouse model of AD. (A-C) Measurements of the plasma (A), brain (B) concentrations, and brain/plasma ratio (C) of CPT at 5 min, 15 min, 30 min, 1h, 2h, 4h, 8h, 24h of post dosing with 2 mg/kg IV or 10 mg/kg PO in SD rats; (D) Body weight measurements of G1 (vehicle) and G2 (CPT-treated) APP(swe)/PS1(deltaE9) mice; (E-G) Latency of G1 (vehicle) and G2 (CPT-treated) APP(swe)/PS1(deltaE9) mice during training sessions (E) or probe trial (F), and number of platform-crossing during probe trial (G) in Morris water maze assays; (H) Measurement of duration in open arm, percent of open arm entries, and percent of time in open arm in the elevated plus maze assay of G1 (vehicle) and G2 (CPT-treated) APP(swe)/PS1(deltaE9) mice; (I) Immunostainings and data quantification showing the effect of CPT treatment on amyloid plaque load and the number of microglia surrounding amyloid plaque in APP(swe)/PS1(deltaE9) mouse brain sections; (J) Measurements of NAD⁺/NADH ratio and H₂O₂ level in whole brain lysates of G1 (vehicle) and G2 (CPT-treated) APP(swe)/PS1(deltaE9) mice. *P < 0.05, **P < 0.01 in Student’s t-test or one-way ANOVA test. PK: Pharmacokinetics; CPT: CPT2008, 6-chloro-3-(2,4-dichloro-5-methoxyphenyl)-2-mecapto-7-methoxyquinazolin-4(3H)-one; AD: Alzheimer’s disease.