Metabolism of Ebracteolata Compound B Studied In Vitro with Human Liver Microsomes, HepG2 Cells, and Recombinant Human Enzymes

2010 ◽  
Vol 38 (12) ◽  
pp. 2157-2165 ◽  
Author(s):  
Xia Zhang ◽  
Yan Yao ◽  
Yan Lou ◽  
Huidi Jiang ◽  
Xiaowen Wang ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes

scholarly journals Nontargeted Metabolomics by High-Resolution Mass Spectrometry to Study the In Vitro Metabolism of a Dual Inverse Agonist of Estrogen-Related Receptors β and γ, DN203368

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 776
Author(s):  
Sin-Eun Kim ◽  
Seung-Bae Ji ◽  
Euihyeon Kim ◽  
Minseon Jeong ◽  
Jina Kim ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
Human Liver ◽  
High Resolution Mass Spectrometry ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Rat Liver Microsomes ◽  
High Resolution Mass ◽  
Resolution Mass

DN203368 ((E)-3-[1-(4-[4-isopropylpiperazine-1-yl]phenyl) 3-methyl-2-phenylbut-1-en-1-yl] phenol) is a 4-hydroxy tamoxifen analog that is a dual inverse agonist of estrogen-related receptor β/γ (ERRβ/γ). ERRγ is an orphan nuclear receptor that plays an important role in development and homeostasis and holds potential as a novel therapeutic target in metabolic diseases such as diabetes mellitus, obesity, and cancer. ERRβ is also one of the orphan nuclear receptors critical for many biological processes, such as development. We investigated the in vitro metabolism of DN203368 by conventional and metabolomic approaches using high-resolution mass spectrometry. The compound (100 μM) was incubated with rat and human liver microsomes in the presence of NADPH. In the metabolomic approach, the m/z value and retention time information obtained from the sample and heat-inactivated control group were statistically evaluated using principal component analysis and orthogonal partial least-squares discriminant analysis. Significant features responsible for group separation were then identified using tandem mass spectra. Seven metabolites of DN203368 were identified in rat liver microsomes and the metabolic pathways include hydroxylation (M1-3), N-oxidation (M4), N-deisopropylation (M5), N,N-dealkylation (M6), and oxidation and dehydrogenation (M7). Only five metabolites (M2, M3, and M5-M7) were detected in human liver microsomes. In the conventional approach using extracted ion monitoring for values of mass increase or decrease by known metabolic reactions, only five metabolites (M1-M5) were found in rat liver microsomes, whereas three metabolites (M2, M3, and M5) were found in human liver microsomes. This study revealed that nontargeted metabolomics combined with high-resolution mass spectrometry and multivariate analysis could be a more efficient tool for drug metabolite identification than the conventional approach. These results might also be useful for understanding the pharmacokinetics and metabolism of DN203368 in animals and humans.

P160 - In vitro metabolism of endosulfan sulfate in human liver microsomes, S9 fractions and hepatocytes

2020 ◽  
Vol 35 (1) ◽  
pp. S71-S72
Author(s):  
Hwa-Kyung Lee ◽  
Jeong-Han Kim ◽  
Tae Yeon Kong ◽  
Won-Gu Choi ◽  
Ju-Hyun Kim ◽  
...  
Keyword(s):  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
In Vitro Metabolism ◽  
Endosulfan Sulfate

scholarly journals CYP3A4 mediated in vitro metabolism of vinflunine in human liver microsomes

2007 ◽  
Vol 28 (1) ◽  
pp. 118-124 ◽  
Author(s):  
Xiao-ping Zhao ◽  
Jiao Zhong ◽  
Xiao-quan Liu ◽  
Guang-ji Wang
Keyword(s):  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
In Vitro Metabolism

Investigations on the metabolic pathways of cyclosporine: II. Elucidation of the metabolic pathways in vitro by human liver microsomes

Xenobiotica ◽  
1991 ◽  
Vol 21 (9) ◽  
pp. 1199-1210 ◽  
Author(s):  
U. Christians ◽  
S. Strohmeyer ◽  
R. Kownatzki ◽  
H.-M. Schiebel ◽  
J. Bleck ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes

Effect of Age on in Vitro Triazolam Biotransformation in Male Human Liver Microsomes

2003 ◽  
Vol 308 (3) ◽  
pp. 874-879 ◽  
Author(s):  
Kiran C. Patki ◽  
Lisa L. von Moltke ◽  
Jerold S. Harmatz ◽  
Leah M. Hesse ◽  
Michael H. Court ◽  
...  
Keyword(s):  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Effect Of Age

scholarly journals Biotransformation of the Flame Retardant 1,2-Dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH) in Vitro by Human Liver Microsomes

2017 ◽  
Vol 51 (18) ◽  
pp. 10511-10518 ◽  
Author(s):  
Khanh-Hoang Nguyen ◽  
Mohamed Abou-Elwafa Abdallah ◽  
Thomas Moehring ◽  
Stuart Harrad
Keyword(s):  
Flame Retardant ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes

scholarly journals Effect of a New Prokinetic Agent DA-9701 Formulated with Corydalis Tuber and Pharbitidis Semen on Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Hye Young Ji ◽  
Kwang Hyeon Liu ◽  
Ji Hyeon Jeong ◽  
Dae-Young Lee ◽  
Hyun Joo Shim ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Udp Glucuronosyltransferase ◽  
Index Value ◽  
Tuber Extract ◽  
Corydalis Tuber

DA-9701 is a new botanical drug composed of the extracts of Corydalis tuber and Pharbitidis semen, and it is used as an oral therapy for the treatment of functional dyspepsia in Korea. The inhibitory potentials of DA-9701 and its component herbs, Corydalis tuber and Pharbitidis semen, on the activities of seven major human cytochrome P450 (CYP) enzymes and four UDP-glucuronosyltransferase (UGT) enzymes in human liver microsomes were investigated using liquid chromatography-tandem mass spectrometry. DA-9701 and Corydalis tuber extract slightly inhibited UGT1A1-mediated etoposide glucuronidation, with 50% inhibitory concentration (IC50) values of 188 and 290 μg/mL, respectively. DA-9701 inhibited CYP2D6-catalyzed bufuralol1′-hydroxylation with an inhibition constant (Ki) value of 6.3 μg/mL in a noncompetitive manner. Corydalis tuber extract competitively inhibited CYP2D6-mediated bufuralol1′-hydroxylation, with aKivalue of 3.7 μg/mL, whereas Pharbitidis semen extract showed no inhibition. The volume in which the dose could be diluted to generate an IC50equivalent concentration (volume per dose index) value of DA-9701 for inhibition of CYP2D6 activity was 1.16 L/dose, indicating that DA-9701 may not be a potent CYP2D6 inhibitor. Further clinical studies are warranted to evaluate thein vivoextent of the observedin vitrointeractions.

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