Cited 3 time in
- Title
- Pharmacokinetic characterization of LW6, a novel hypoxia-inducible factor-1α (HIF-1α) inhibitor in mice
- Author(s)
- J Y Lee; K Lee; K Lee; Jong Soon Kang; Min Ju Kim; D G Yoo; J A Kim; E J Shin; S J Oh
- Bibliographic Citation
- Molecules, vol. 26, no. 8, pp. 2226-2226
- Publication Year
- 2021
- Abstract
- LW6, an (aryloxyacetylamino)benzoic acid derivative, was recently identified to be an inhibitor of hypoxia-inducible factor-1α (HIF-1α), which is an attractive target for cancer therapeutics. Although LW6 is known to act by inhibiting the accumulation of HIF-1α, pharmacokinetics needs to be evaluated to assess its potential as an anti-tumor agent. Here, we investigated the plasma pharmacokinetics and metabolism of LW6 in mice. LW6 exhibited a small volume of distribution (0.5 ± 0.1 L/kg), and a short terminal half-life (0.6 ± 0.1 h). Following intravenous or oral administration, LW6 was rapidly converted to its active metabolite, (4-adamantan-1-yl-phenoxy)acetic acid (APA). Although LW6 was rapidly absorbed, its oral bioavailability, estimated using AUClast values, was low (1.7 ± 1.8%). It was slowly degraded in mouse liver microsomes (t1/2 > 1 h) and serum (t1/2 > 6 h). About 54% or 44.8% of LW6 was available systemically as APA in the mouse after a single intravenous or oral administration, respectively. Thus, our results indicated the need to simultaneously consider the active metabolite as well as the parent compound for successful evaluation during lead optimization.
- Keyword
- LW6Mice pharmacokineticsLiver microsomesMetabolismCaco-2 cells
- ISSN
- 1420-3049
- Publisher
- MDPI
- DOI
- http://dx.doi.org/10.3390/molecules26082226
- Type
- Article
- Appears in Collections:
- Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
- Files in This Item:
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