- P-ISSN 2233-4203
- E-ISSN 2093-8950
- P-ISSN2233-4203
- E-ISSN2093-8950
- ESCI, SCOPUS, KCI
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Characterization of Preclinical in Vitro and in Vivo Pharmacokinetic Properties of KPLA-012, a Benzopyranyl 1,2,3-Triazole Compound, with Anti-Angiogenetic and Anti-Tumor Progressive Effects
Mass Spectrometry Letters / Mass Spectrometry Letters, (P)2233-4203; (E)2093-8950
2018, v.9 no.2, pp.61-65
https://doi.org/10.5478/MSL.2018.9.2.61
(Kyungpook National University)
(Kyungpook National University)
(Dankook University)
(Kyungpook National University)
(Kyungpook National University)
(Dankook University)
(Kyungpook National University)
Nam,
S. J., Lee,
T., Choi,
M., &
Song,
I.
(2018). Characterization of Preclinical in Vitro and in Vivo Pharmacokinetic Properties of KPLA-012, a Benzopyranyl 1,2,3-Triazole Compound, with Anti-Angiogenetic and Anti-Tumor Progressive Effects. Mass Spectrometry Letters, 9(2), 61-65, https://doi.org/10.5478/MSL.2018.9.2.61
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Abstract
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.
- keywords
- KPLA-012, benzopyranyl 1, 2, 3-triazole compound, pharmacokinetics, metabolic instability
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- Submission Date
- 2018-06-01
- Revised Date
- 2018-06-19
- Accepted Date
- 2018-06-19
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