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)
Article
Chemistry, Multidisciplinary
Gustavo Perez Ortiz, John D. Sidda, Emmanuel L. C. de los Santos, Catherine B. Hubert, Sarah M. Barry
Summary: The antimycobacterial peptides rufomycins exhibit antibiotic activity due to oxidative tailoring of the cyclic peptide. Cytochrome P450s RufS and RufM play roles in regioselective epoxidation and alkyl oxidation, creating a complex product profile dependent on redox partner availability. Additionally, in vitro one pot conversion of rufomycin B to rufomycin C has been successfully demonstrated.
CHEMICAL COMMUNICATIONS
(2021)
Article
Food Science & Technology
Feng Zhang, Jian Huang, Wei Liu, Chao-Ran Wang, Yan-Fang Liu, Dong-Zhu Tu, Xin-Miao Liang, Ling Yang, Wei-Dong Zhang, Hong-Zhuan Chen, Guang-Bo Ge
Summary: The study found that Qingfei Paidu decoction can inhibit multiple drug-metabolizing enzymes, with a significant inhibitory effect on CYP3A. In vivo experiments showed that co-administration of QPD with lopinavir could prolong the half-life of lopinavir and increase its AUC, and further investigations revealed that Fructus Aurantii Immaturus in QPD may cause significant loss of CYP3A activity.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Lei Hou, Yingying Zhao, Shiyu Zhao, Xuexia Zhang, Xia Yao, Jianjun Yang, Ziteng Wang, Shuaibing Liu
Summary: This study systematically characterized the UGTs enzymes involved in the formation of M4 and the inhibitory effects of ciprofol and its metabolite M4 on P450s enzymes. In vitro-in vivo extrapolation and PBPK simulations were performed to predict potential drug-drug interactions caused by ciprofol.
CHEMICO-BIOLOGICAL INTERACTIONS
(2024)
Article
Chemistry, Multidisciplinary
Feng Zhang, Wei Liu, Jian Huang, Qi-long Chen, Dan-dan Wang, Li-wei Zou, Yong-fang Zhao, Wei-dong Zhang, Jian-guang Xu, Hong-zhuan Chen, Guang-bo Ge
Summary: Jingyin granules, an antiviral herbal medicine, are commonly used to treat viral infections. Research shows that the herbal extract of Jingyin granules can inhibit human drug-metabolizing enzymes and modulate the plasma exposure and half-life of certain drugs.
ACTA PHARMACOLOGICA SINICA
(2022)
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
Biochemistry & Molecular Biology
Manuel Sellner, Andre Fischer, Charleen G. Don, Martin Smiesko
Summary: Research using molecular dynamics simulations and protein-protein docking revealed the mechanism of conformational changes between cytochrome P450 enzymes and cytochrome P450 reductase, as well as proposed new conformational transition mechanisms and structural mechanisms for susceptibility to redox states.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Melina Lopez, Pedro F. Malacarne, Anna Gajos-Draus, Xinxin Ding, Andreas Daiber, Jon O. Lundberg, Stefan Offermanns, Ralf P. Brandes, Flavia Rezende
Summary: The study suggests that metabolism by vascular CYPs does not contribute to the pharmacological function of organic nitrates, while ALDH2 plays an important role in activating organic nitrates.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Soudeh Bahramian Nasab, Ahmad Homaei, Roberto Fernandez-Lafuente, Jon Del Arco, Jesus Fernandez-Lucas
Summary: The use of marine enzymes as catalysts for biotechnological applications is a hot topic. In this study, a liver NADPH-dependent cytochrome P450 reductase (CPR) from the marine fish Liza klunzingeri (LkCPR) was isolated, purified and biochemically characterized. LkCPR showed remarkable catalytic features, such as a wide range of pH and temperature stability, high catalytic activity, and highest thermostability among reported CPRs. These findings suggest that LkCPR has great potential as a biocatalyst.
Article
Biochemistry & Molecular Biology
He Liu, Zixia Hu, Ningning Han, Yi Yang, Guode Zhao, Mengdie Su, Yue Zhang, Weiwei Li, Ying Peng, Jiang Zheng
Summary: The study aimed to investigate the metabolic activation of MTX and its possible correlation with cytotoxicity. An oxidative metabolite (M1) and a GSH conjugate (M2) were observed in S9 fraction incubations and rat primary hepatocyte culture after MTX exposure. M1 and M2 were also detected in the bile of MTX-treated rats. CYP2A6 was found to be the dominant enzyme responsible for the oxidation of MTX. Inhibition of CYP2A6 and sulfotransferase significantly decreased the formation of M2. Pretreatment of primary hepatocytes with inhibitors reduced the susceptibility to MTX-induced cytotoxicity.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Biochemistry & Molecular Biology
Shuaibing Liu, Ziteng Wang, Eric Chan, Yibo Zhao, Jian Kang, Xiaojian Zhang, Xin Tian
Summary: Vicagrel, an antiplatelet drug candidate targeting platelet P2Y12 receptor, exhibits potent inhibitory effects on several enzymes, including CYP2B6, CYP2C19, and UGT1A6. Physiological-based pharmacokinetic simulation suggests no clinically significant drug-drug interactions between vicagrel and bupropion or S-mephenytoin.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Review
Pharmacology & Pharmacy
Aleksi Tornio, Anne M. Filppula, Janne T. Backman
Summary: Multimorbidity, polypharmacotherapy, and drug interactions are prevalent in the ageing population. Drug-drug interactions can have negative health impacts, requiring translational research approaches to fully characterize the mechanisms, clinical effects, and implications of CYP-mediated DDIs.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Li Ma, Tianjian Sun, Yunjie Liu, Yue Zhao, Xiaohui Liu, Yuxuan Li, Xinwei Chen, Lin Cao, Qianqian Kang, Jiawei Guo, Lei Du, Wei Wang, Shengying Li
Summary: In this study, cytochrome P450 BM3 was engineered into peroxygenases through directed evolution. These modified enzymes were used to selectively oxidize indole derivatives to produce a variety of indigoid pigments with a reduced band gap. These indigoid photocatalysts show promise for the development of new organic electronic devices.
SYNTHETIC AND SYSTEMS BIOTECHNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Jie Chen, Sheng Dong, Wenhan Fang, Yiping Jiang, Zhifeng Chen, Xiangquan Qin, Cong Wang, Haifeng Zhou, Longyi Jin, Yingang Feng, Binju Wang, Zhiqi Cong
Summary: We report the selective hydroxylation of alkylbenzenes using an engineered P450 peroxygenase driven by a dual-functional small molecule (DFSM). By combining different P450BM3 variants with DFSMs, more than half of all possible hydroxylated products were obtained from each substrate with high regioselectivity (>99%), enantioselectivity (>99% ee), and high total turnover numbers (up to 80963). Synergistic effects between exogenous DFSMs and the protein environment controlled the regio- and enantioselectivity, as revealed by crystal structure analysis, molecular dynamic simulations, and theoretical calculations. This work has implications for exogenous-molecule-modulated enzymatic regiodivergent and enantioselective hydroxylation with potential applications in synthetic chemistry.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Li Zhang, Bo Zhang, Ao Zhu, Shuang He Liu, Rui Wu, Xuan Zhang, Zhengren Xu, Ren Xiang Tan, Hui Ming Ge
Summary: This study reveals the biosynthesis of phomactin natural products, which only requires two enzymes and involves rearrangement of the diterpene scaffold. The mechanism of phomactin biosynthesis was investigated through isotope labeling experiments and crystal complex analysis, providing insights into the efficient production of phomactins using synthetic biology approaches.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)