Table 5. Liver Microsomal Stability and Pharmacokinetic Parameters of CLPP-1071 and ONC212 in Mice.
| compds | CLPP-1071 | ONC212 | testosterone |
|---|---|---|---|
| liver microsomal stabilitya | |||
| T1/2 (min) H/R | 13.7/6.89 | 10.24/7.12 | 8.69/0.723 |
| Clint (mL/min/kg) H/R | 0.253/0.503 | 0.338/0.487 | 0.399/4.80 |
| Clapp (mL/min/kg) H/R | 296/906 | 396/876 | 467/8634 |
| Clh (mL/min/kg) H/R | 19.3/52.0 | 19.7/51.9 | 19.8/54.8 |
| Eh (%) | 93.5/94.3 | 95.0/94.1 | 95.8/99.4 |
| PO PK parameters at50 mg/kgin miceb | |||
| T1/2 (h) | 1.45 ± 0.33 | 2.03 ± 0.30 | |
| Tmax (h) | 0.50 ± 0.43 | 0.58 ± 0.38 | |
| Cmax (ng/mL) | 3423 ± 570 | 2020 ± 344 | |
| AUC0–t (h*ng/mL) | 9010 ± 1322 | 5715 ± 472 | |
| AUC0–∞ (h*ng/mL) | 9839 ± 990 | 6841 ± 57 | |
| MRT (h) | 2.61 ± 0.41 | 3.26 ± 0.00 | |
a
Testosterone as a reference compound. Abbreviations: Cl: plasma clearance and T1/2 = terminal half-life (H/R = human/rat).
b
Data are presented as the mean value of triplicate samples ±standard deviation (n = 3). ONC212 and CLPP-1071 compounds were administered orally at 50 mg/kg (0.5% CMC-Na) in ICR female mice. Plasma samples were collected at 0.083, 0.25, 0.5, 1, 2, 4, 6, and 24 h from three mice at each time point and analyzed by LC–MS/MS.