Pharmacokinetic characterization of LW6, a novel hypoxia-inducible factor-1α (HIF-1α) inhibitor in mice

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dc.contributor.authorJ Y Lee-
dc.contributor.authorK Lee-
dc.contributor.authorK Lee-
dc.contributor.authorJong Soon Kang-
dc.contributor.authorMin Ju Kim-
dc.contributor.authorD G Yoo-
dc.contributor.authorJ A Kim-
dc.contributor.authorE J Shin-
dc.contributor.authorS J Oh-
dc.date.accessioned2021-05-04T03:30:33Z-
dc.date.available2021-05-04T03:30:33Z-
dc.date.issued2021-
dc.identifier.issn14203049-
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/24288-
dc.description.abstractLW6, 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.-
dc.publisherMDPI-
dc.titlePharmacokinetic characterization of LW6, a novel hypoxia-inducible factor-1α (HIF-1α) inhibitor in mice-
dc.title.alternativePharmacokinetic characterization of LW6, a novel hypoxia-inducible factor-1α (HIF-1α) inhibitor in mice-
dc.typeArticle-
dc.citation.titleMolecules-
dc.citation.number8-
dc.citation.endPage2226-
dc.citation.startPage2226-
dc.citation.volume26-
dc.contributor.affiliatedAuthorJong Soon Kang-
dc.contributor.affiliatedAuthorMin Ju Kim-
dc.contributor.alternativeName이지윤-
dc.contributor.alternativeName이기호-
dc.contributor.alternativeName이경-
dc.contributor.alternativeName강종순-
dc.contributor.alternativeName김민주-
dc.contributor.alternativeName유동구-
dc.contributor.alternativeName김정아-
dc.contributor.alternativeName신은진-
dc.contributor.alternativeName오수진-
dc.identifier.bibliographicCitationMolecules, vol. 26, no. 8, pp. 2226-2226-
dc.identifier.doi10.3390/molecules26082226-
dc.subject.keywordLW6-
dc.subject.keywordMice pharmacokinetics-
dc.subject.keywordLiver microsomes-
dc.subject.keywordMetabolism-
dc.subject.keywordCaco-2 cells-
dc.subject.localMetabolism-
dc.description.journalClassY-
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
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