TABLE 1

In vitro metabolic stability of KZR-616 and analogs in HLMs and MLMs in the presence or absence of NADPH

Predicted t1/2 and Clint were obtained from in vitro assays. Data are presented as mean ±

S.D. (n = 3). The conc. of test compound in the assays was 1 µM. LM binding (%) of test compound was conducted using ultracentrifugation.

IDKZR-616KZR-059177KZR-059240
SpeciesHLMMLMHLMMLMHLMMLM
(NADPH)(−)(+)(−)(+)(−)(+)(−)(+)(−)(+)(−)(+)
t1/2 (min)194 ± 14.076.0 ± 3.797.1 ± 12.616.0 ± 0.43339.1 ± 1.0716.2 ± 0.79324.2 ± .71912.4 ± 2.78NA45.6 ± 4.61NA18.1 ± 2.16
Clint (μl/min/mg)14.3 ± 1.0136.5 ± 1.8028.6 ± 3.67173 ±.4.6270.9 ± 1.97172 ± 8.512860 ± 84.55717 ± 1274NA51.2 ± 0.621NA154 ± 18.4
LM binding (%)12.37.40NANA20.421.3
  • NA, not applicable (no value was obtained).