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- P-ISSN 2233-4203
- E-ISSN 2093-8950
KPLA-012, a benzopyranyl 1,2,3-triazole compound, is considered a potent HIF-1α inhibitor based on the chemical library screening, and is known to exhibit anti-angiogenetic and anti-tumor progressive effects. The aim of this study was to investigate the pharmacokinetic properties of KPLA-012 in ICR mice and to investigate in vitro characteristics including the intestinal absorption, distribution, metabolism, and excretion of KPLA-012. The oral bioavailability of KPLA-012 was 33.3% in mice. The pharmacokinetics of KPLA-012 changed in a metabolism-dependent manner, which was evident by the low recovery of parent KPLA-012 from urine and feces and metabolic instability in the liver microsomes. However, KPLA-012 exhibited moderate permeability in Caco-2 cells (3.1 × 10 -6 cm/s) and the metabolic stability increased in humans compared to that in mice (% remaining after 1 h; 47.4% in humans vs 14.8% in mice). Overall, the results suggest that KPLA-012 might have more effec- tive pharmacokinetic properties in humans than in mice although further studies on its metabolism are necessary.
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