Article
Biochemistry & Molecular Biology
Petar M. Mitrasinovic
Summary: The study revealed that chrysin has the largest inhibitory effect on CYP3A4, while quercetin and flavopiridol serve as representative examples of structurally different flavonoids. The inhibition parameters for these compounds were evaluated using the calibrated QM/MM strategy, aiding in quantitatively understanding the functional behavior of the whole flavonoid family. Additionally, a kinetic threshold for further assessment of the time-dependent inhibition of CYP3A4 by flavonoids was explored.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Analytical
Michael Riffle, Michael R. Hoopmann, Daniel Jaschob, Guo Zhong, Robert L. Moritz, Michael J. MacCoss, Trisha N. Davis, Nina Isoherranen, Alex Zelter
Summary: The study introduces Magnum and Limelight, an algorithm and software package for the identification and visualization of xenobiotic-protein adducts. Through validation and application, the methods and software enable accurate identification of xenobiotic-protein adducts and fill the gap in comprehensive data visualization tools in the field of open-mass searching.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Physical
Nico D. Fessner, Christopher Grimm, Matic Srdic, Hansjoerg Weber, Wolfgang Kroutil, Ulrich Schwaneberg, Anton Glieder
Summary: This study explores the synthetic potential of human P450 3A4 in diversifying natural product classes, resulting in the identification of 31 authentic human metabolites. With efficient expression levels in P. pastoris, this biocatalyst shows promising results for modifying natural products in a one-step fashion.
Article
Pharmacology & Pharmacy
Przemyslaw J. Danek, Agnieszka Basinska-Ziobron, Jacek Wojcikowski, Wladyslawa A. Daniel
Summary: The study found that levomepromazine and clozapine can induce the expression of CYP3A4 in human hepatocytes, but do not have a significant effect on the activity of other CYP enzymes. Further in vivo studies are needed to confirm the induction of CYP3A4 by these drugs and to assess their impact on drug metabolism.
PHARMACOLOGICAL REPORTS
(2021)
Article
Multidisciplinary Sciences
Sumiko Ohnami, Akane Naruoka, Mitsuhiro Isaka, Maki Mizuguchi, Sou Nakatani, Fukumi Kamada, Yuji Shimoda, Ai Sakai, Keiichi Ohshima, Keiichi Hatakeyama, Kouji Maruyama, Yasuhisa Ohde, Hirotsugu Kenmotsu, Toshiaki Takahashi, Yasuto Akiyama, Takeshi Nagashima, Kenichi Urakami, Shumpei Ohnami, Ken Yamaguchi
Summary: The differences in genetic susceptibility to lung adenocarcinoma and squamous cell carcinoma are still not clear. Researchers developed a gene sequencing panel to detect germline variants in these two types of cancer. The study found that certain gene variants were associated with an increased risk of squamous cell carcinoma, while whole-gene deletion was associated with adenocarcinoma.
SCIENTIFIC REPORTS
(2022)
Article
Plant Sciences
Saneesh Kumar, Patrick J. Bouic, Bernd Rosenkranz
Summary: The study evaluated the effects of Withania somnifera root extracts on cytochromes P450, finding that they may cause clinically significant herb-drug interactions by affecting the metabolism pathway of drugs such as rifampicin.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Immunology
Kristina Jonsson-Schmunk, Romi Ghose, Maria A. Croyle
Summary: The study discovered that infection and vaccines can have an impact on the activity of the CYP3A4 enzyme in liver cells, which may lead to impaired drug metabolism. Therefore, it is essential to evaluate the effects of new vaccines and emerging pathogens on metabolic enzymes in the clinical assessment of global pathogen vaccines.
EXPERT REVIEW OF VACCINES
(2021)
Article
Chemistry, Multidisciplinary
Nicholas Toupin, Sean J. Steinke, Sandeep Nadella, Ao Li, Thomas N. Rohrabaugh, Eric R. Samuels, Claudia Turro, Irina F. Sevrioukova, Jeremy J. Kodanko
Summary: Metal-based inhibitors of CYP3A4 show potent and selective inhibition of the drug metabolizing enzyme, suggesting potential clinical applications in enhancing the therapeutic efficacy of anticancer drugs.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Review
Pharmacology & Pharmacy
Yurong Song, Chenxi Li, Guangzhi Liu, Rui Liu, Youwen Chen, Wen Li, Zhiwen Cao, Baosheng Zhao, Cheng Lu, Yuanyan Liu
Summary: Drug metabolism is a critical process for the removal of unwanted substances from the body, with CYP enzymes playing essential roles in the liver and intestine. In addition to their excretory function, CYP enzymes can impact treatment outcomes and drug actions, with recent literature highlighting their potential influence on drug response.
CLINICAL PHARMACOKINETICS
(2021)
Article
Pharmacology & Pharmacy
Laura Maria Fuhr, Fatima Zahra Marok, Uwe Fuhr, Dominik Selzer, Thorsten Lehr
Summary: Grapefruit is a potent inhibitor of CYP3A4, which can affect the metabolism of CYP3A4 victim drugs for up to 24 hours after consumption. This study developed a physiologically-based pharmacokinetic model to simulate and predict the effect of grapefruit juice on the plasma concentration-time profiles of various CYP3A4 victim drugs.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Environmental Sciences
Salah A. Sheweita, Ahmed Abd El Rafea, Sabah G. Elbana
Summary: Exposure to cadmium is related to liver and kidney diseases. The mechanisms of cadmium's contribution to these diseases are unclear. This study found that cadmium exposure induced oxidative stress, inhibited antioxidant enzyme activities, and altered drug-metabolizing enzyme activities in the liver. Silymarin and garlic extract were found to protect against cadmium toxicity and restore enzyme activities to normal levels. This research has important implications for the protection and prevention of cadmium-related health effects.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2023)
Article
Food Science & Technology
Petr Pavek, Jan Dusek, Tomas Smutny, Lukas Lochman, Radim Kucera, Josef Skoda, Lucie Smutna, Rajamanikkam Kamaraj, Pavel Soucek, Radim Vrzal, Zdenek Dvorak
Summary: This study suggests that VDR or vitamin D supplementation is unlikely to significantly influence liver detoxification enzymes apart from CYP3A4.
MOLECULAR NUTRITION & FOOD RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
F. Peter Guengerich, Kevin D. McCarty, Jesse G. Chapman
Summary: Cytochrome P450 (P450) 3A4 is a crucial enzyme in drug metabolism, with certain inhibitors showing distinct kinetic characteristics in inhibiting its activity. The exact mechanisms of P450 3A4 inhibition by various drugs are still unclear in many cases.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Amna Ghith, John B. Bruning, Stephen G. Bell
Summary: The CYP124 family of cytochrome P450 enzymes plays a role in the metabolism of methyl branched lipids and cholesterol derivatives. By comparing the equivalent enzymes from Mycobacterium marinum and Mycobacterium tuberculosis, differences in substrate binding and catalytic oxidation were observed. The CYP124 enzyme from M. tuberculosis showed a larger shift to the ferric high-spin state and displayed distinct UV-vis spectra compared to the enzyme from M. marinum when binding cholesterol derivatives. However, both enzymes maintained selectivity for oxidation at the omega-carbon of a branched chain.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Pharmacology & Pharmacy
Line Skute Braten, Tore Haslemo, Marin M. Jukic, Maxim Ivanov, Magnus Ingelman-Sundberg, Espen Molden, Marianne Kristiansen Kringen
Summary: Escitalopram, a commonly used antidepressant drug, shows substantial interindividual variation in clinical response, which can be attributed to the polymorphic nature of the CYP2C19 gene. A novel CYP2C-haplotype associated with ultrarapid metabolism of escitalopram was identified in this study.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)