Search

Your search keyword '"Lee, Rowoon"' showing total 12 results
Start Over Author "Lee, Rowoon"
12 results on '"Lee, Rowoon"'

3. Inhibition of cytochrome P450 2B6 by Astragalus extract mixture HT042

Author

Kim, Harim, Lee, Yejin, Kim, Vitchan, Lee, Rowoon, Bae, Soo Kyung, Kwak, Mi-Kyoung, Lee, Sung Hoon, and Kim, Donghak

Abstract

Astragalus extract mixture (AEM) HT042 is a functional food approved by the MFDS (Korean FDA) for increasing height. It comprises a mixture of three standardized extracts from Astragalus membranaceusroot, Eleutherococcus senticosusstem, and Phlomis umbrosaroot. In this study, drug–functional food interaction was analyzed using six major human cytochrome P450 enzymes. The inhibitory effect of AEM HT042 on P450 activities was studied using a P450–NADPH P450 reductase reconstitution system. Among the six P450 enzymes (1A2, 2A6, 2B6, 2D6, 2C9, and 3A4), only P450 2B6 activity was markedly decreased by AEM HT042 addition. The bupropion hydroxylation activity of P450 2B6 was analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS). A calculated IC50value of 10.62 µg/ml was obtained. To identify the inhibitory compounds in the mixture, four active compounds in AEM HT042 were analyzed. Shanzhiside methylester exhibited inhibitory effects on P450 2B6, whereas formononetin, eleutheroside E, and sesamoside did not affect P450 2B6 activity at all. Our results suggest that shanzhiside methylester in AEM HT042 is responsible for the inhibitory effect on P450 2B6 metabolism. Characterization of the inhibitory effect on P450 can help determine the safe administration of functional foods along with many clinical drugs that are metabolized by P450.

Published
2024
Full Text
View/download PDF

5. TNP and its analogs: Modulation of IP6K and CYP3A4 inhibition

Author

Lee, Seulgi, primary, Park, Bernie Byeonghoon, additional, Kwon, Hongmok, additional, Kim, Vitchan, additional, Jeon, Jang Su, additional, Lee, Rowoon, additional, Subedi, Milan, additional, Lim, Taehyeong, additional, Ha, Hyunsoo, additional, An, Dongju, additional, Kim, Jaehoon, additional, Kim, Donghak, additional, Kim, Sang Kyum, additional, Kim, Seyun, additional, and Byun, Youngjoo, additional

Published
2021
Full Text
View/download PDF

12. TNP and its analogs: Modulation of IP6K and CYP3A4 inhibition.

Author

Lee S, Park BB, Kwon H, Kim V, Jeon JS, Lee R, Subedi M, Lim T, Ha H, An D, Kim J, Kim D, Kim SK, Kim S, and Byun Y

Subjects
Dose-Response Relationship, Drug, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Humans, Molecular Structure, Phosphotransferases (Phosphate Group Acceptor) metabolism, Structure-Activity Relationship, Cytochrome P-450 CYP3A metabolism, Enzyme Inhibitors pharmacology, Phosphotransferases (Phosphate Group Acceptor) antagonists & inhibitors
Abstract

Inositol hexakisphosphate kinase (IP6K) is an important mammalian enzyme involved in various biological processes such as insulin signalling and blood clotting. Recent analyses on drug metabolism and pharmacokinetic properties on TNP ( N 2 -( m -trifluorobenzyl), N 6 -( p -nitrobenzyl)purine), a pan-IP6K inhibitor, have suggested that it may inhibit cytochrome P450 (CYP450) enzymes and induce unwanted drug-drug interactions in the liver. In this study, we confirmed that TNP inhibits CYP3A4 in type I binding mode more selectively than the other CYP450 isoforms. In an effort to find novel purine-based IP6K inhibitors with minimal CYP3A4 inhibition, we designed and synthesised 15 TNP analogs. Structure-activity relationship and biochemical studies, including ADP-Glo kinase assay and quantification of cell-based IP7 production, showed that compound 9 dramatically reduced CYP3A4 inhibition while retaining IP6K-inhibitory activity. Compound 9 can be a tool molecule for structural optimisation of purine-based IP6K inhibitors.

Published
2022
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results