Venlafaxine upregulates cortical catechol-O-methyltransferase expression and activity in rats and mice [0.03%]
文拉法辛通过上调皮质多巴胺β-羟基酶的表达和活性来降低小鼠和大鼠纹状体中左旋多巴转化为多巴胺的比例
Liqiang Qian,Zijun Xu,Qianli Ye et al.
Liqiang Qian et al.
Clinical trials have demonstrated that venlafaxine affects brain functions in healthy subjects, but its underlying mechanisms remain unclear. The objective of this study was to systematically evaluate the effects of venlafaxine on the expre...
Mechanism-guided untargeted-to-targeted lipidomics identifies phosphatidylcholine 38:4 in rat bile as an Abcb4/Mdr2 inhibition marker [0.03%]
基于机制的非靶标向靶标脂质组学鉴定磷脂酰胆碱38:4为Abcb4/mrp3抑制标志物
Renmeng Liu,Zachary Rabow,Tingyuan Yang et al.
Renmeng Liu et al.
Drug-induced liver injury can occur when the canalicular phospholipid floppase multidrug resistance protein 3 (Mdr2 in rodents) is inhibited, but there is still a lack of early biomarkers to detect this risk. In this study, bile duct-cannul...
Identification, synthesis, and characterization of a unique N-glucuronide of an acid metabolite of camizestrant (AZD9833) in humans [0.03%]
人类中一种新型酸代谢产物（AZD9833）N-葡萄糖苷的鉴定、合成和表征
Zhoupeng Zhang,Stephen Wilkinson,Peter W A Howe et al.
Zhoupeng Zhang et al.
Camizestrant (AZD9833) is a next-generation oral selective estrogen receptor (ER) degrader and complete ER antagonist in phase 3 clinical development for the treatment of ER-positive breast cancer. Metabolite M14, an N-glucuronide of the ac...
Lysine- and cysteine-based protein adduction resulting from metabolic activation of fraxinellone in Dictamni Cortex [0.03%]
Dictamni Cortex 代谢活化产物引起的赖氨酸和半胱氨酸修饰研究
Jie Pan,Enfu Zhang,Chutian Wu et al.
Jie Pan et al.
Dictamni Cortex (DC) has been associated with herb-induced liver injury, and fraxinellone (FRA), a furan-containing constituent, is implicated as a major hepatotoxic component. However, direct evidence linking FRA bioactivation to hepatic p...
Overlooked aspects of scaling enzyme activity through abundance across tissues and individuals: Insights from kcat measurements in matched liver and intestinal samples [0.03%]
通过组织和个体间的酶丰度调控酶活性的未解问题：来自匹配肝肠样本kcat测定的启示
Zubida M Al-Majdoub,Jill Barber,Amin Rostami-Hodjegan et al.
Zubida M Al-Majdoub et al.
Prediction of human intestinal metabolism within physiologically based pharmacokinetic models is now well established within drug development. Extrapolation of in vitro kinetic parameters accounts for differences in abundance between differ...
Prevalence of non-cytochrome P450-mediated metabolism in food and drug administration-approved drugs: 2005-2024 [0.03%]
2005-2024年FDA批准药物中非细胞色素P450介导代谢的流行率
Matthew A Cerny
Matthew A Cerny
Based on literature reports of the increasing importance of non-cytochrome P450 (non-P450) metabolism, an initial evaluation of the prevalence of non-P450 metabolism was undertaken and published in 2016. This initial evaluation covered 10 y...
Profiling RNA metabolism to understand tissue and subcellular clearance of therapeutic RNA [0.03%]
剖析RNA代谢以了解组织和亚细胞治疗性RNA清除机制
Harvey Andersen,Ryan Hill,Alec Bell et al.
Harvey Andersen et al.
Recent clinical success for RNA therapeutics supports the promise of these modalities to unlock additional drug targets with pharmacodynamic responses that are considerably more durable than other drug classes. Metabolic clearance in tissue...
Lirafugratinib attenuates ABCG2-dependent drug efflux and restores chemosensitivity in multidrug-resistant nonsmall cell lung cancer cells [0.03%]
Lirafugratinib抑制ABCG2依赖性药物外排并恢复多药耐药非小细胞肺癌细胞的化学敏感性
Chung-Pu Wu,Yen-Ching Li,Bing-Huan Lin et al.
Chung-Pu Wu et al.
The therapeutic efficacy of many anticancer drugs is frequently compromised by multidrug resistance, a process often driven by elevated activity of ATP-binding cassette (ABC) efflux pumps in tumor cells. These membrane transporters actively...
Inhibitory effects of Δ8-tetrahydrocannabinol on nicotine metabolism and implications as a smoking cessation agent [0.03%]
Δ8-四氢大麻酚对尼古丁代谢的抑制作用及其作为戒烟药物的意义
Mengqi Zhao,Shaman Luo,Philip Lazarus
Mengqi Zhao
Tobacco use remains the leading cause of preventable death worldwide. The major metabolic pathway for nicotine, the addictive component in tobacco, is via cytochrome P450 (CYP) 2A6-mediated metabolism to cotinine. Cannabidiol has been shown...
Drug-drug interaction by metabolites: Challenges and solutions during therapeutics innovation [0.03%]
药物代谢物的药物相互作用：治疗创新过程中的挑战和解决方案
Shujun Fu,Feifei Yu,Tao Sun et al.
Shujun Fu et al.
The direct effects of drug metabolites on efficacy and safety have been evaluated carefully according to the regulatory guidelines by major authorities such as the International Council for Harmonisation of Technical Requirements for Pharma...