Pharmacokinetic Characterization of LW6, a Novel Hypoxia-Inducible Factor-1 alpha (HIF-1 alpha) Inhibitor in Mice
DC Field | Value | Language |
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dc.contributor.author | Lee, Ji-Yoon | - |
dc.contributor.author | Lee, Kiho | - |
dc.contributor.author | Lee, Kyeong | - |
dc.contributor.author | Kang, Jong Soon | - |
dc.contributor.author | Kim, Min Ju | - |
dc.contributor.author | Yoo, Dong Gu | - |
dc.contributor.author | Kim, Jung Ah | - |
dc.contributor.author | Shin, Eun Jin | - |
dc.contributor.author | Oh, Soo Jin | - |
dc.date.accessioned | 2021-11-22T07:41:01Z | - |
dc.date.available | 2021-11-22T07:41:01Z | - |
dc.date.created | 2021-08-30 | - |
dc.date.issued | 2021-04 | - |
dc.identifier.issn | 1420-3049 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/128331 | - |
dc.description.abstract | LW6, an (aryloxyacetylamino)benzoic acid derivative, was recently identified to be an inhibitor of hypoxia-inducible factor-1 alpha (HIF-1 alpha), which is an attractive target for cancer therapeutics. Although LW6 is known to act by inhibiting the accumulation of HIF-1 alpha, 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 AUC(last) values, was low (1.7 +/- 1.8%). It was slowly degraded in mouse liver microsomes (t(1/2) > 1 h) and serum (t(1/2) > 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.language | English | - |
dc.language.iso | en | - |
dc.publisher | MDPI | - |
dc.title | Pharmacokinetic Characterization of LW6, a Novel Hypoxia-Inducible Factor-1 alpha (HIF-1 alpha) Inhibitor in Mice | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, Kiho | - |
dc.identifier.doi | 10.3390/molecules26082226 | - |
dc.identifier.scopusid | 2-s2.0-85105197009 | - |
dc.identifier.wosid | 000644620100001 | - |
dc.identifier.bibliographicCitation | MOLECULES, v.26, no.8 | - |
dc.relation.isPartOf | MOLECULES | - |
dc.citation.title | MOLECULES | - |
dc.citation.volume | 26 | - |
dc.citation.number | 8 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.subject.keywordAuthor | LW6 | - |
dc.subject.keywordAuthor | mice pharmacokinetics | - |
dc.subject.keywordAuthor | liver microsomes | - |
dc.subject.keywordAuthor | metabolism | - |
dc.subject.keywordAuthor | Caco-2 cells | - |
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