Baseline variations in in vivo cytochrome P450 3A-dependent phenotypes evaluated using concentrations of endogenous or deuterium-labeled cortisol and their 6β-hydroxylated metabolites in 103 cynomolgus monkeys and 20 humanized-liver mice transplanted with hepatocytes [0.03%]
基于体内细胞色素P450 3A表型的基线差异评价：使用恒河猴和人源化肝脏小鼠中内源性或二氯素标记皮质醇及其6β-羟基化代谢物的浓度测定
Shotaro Uehara,Yuichiro Higuchi,Suguru Fukuda et al.
Shotaro Uehara et al.
Drug exposure, in terms of plasma concentrations, may be affected by individual differences in intrinsic drug-metabolizing enzymes as much as by exogenous drug interactions. However, baseline variations in drug-metabolizing enzyme activitie...
Evaluating alterations in drug-metabolizing enzymes in cancer: insights from in vivo, in vitro, and biomarker studies [0.03%]
基于体内、体外及生物标志物研究探讨癌症中代谢酶的改变
Eman El-Khateeb,Oliver Hatley,Iain Gardner et al.
Eman El-Khateeb et al.
Drug-metabolizing enzymes (DMEs) are critical determinants of drug elimination, yet hepatic and intestinal DME changes between cancer and healthy subjects remain controversial. To address this uncertainty, a physiologically based pharmacoki...
Ketone reduction drives major circulating metabolites of GDC-8264 in humans [0.03%]
酮还原驱动GDC-8264在人体中的主要循环代谢物
Shuai Wang,Susan Wong,Antonio DiPasquale et al.
Shuai Wang et al.
GDC-8264 (flizasertib) is a small molecule inhibitor of receptor-interacting serine/threonine-protein kinase 1 currently in clinical development. From a phase I dose escalation study in healthy subjects, 2 major circulating metabolites, M5 ...
Mass spectrometry imaging uncovers drug-induced lipid alterations in the mouse heart [0.03%]
基于质谱成像的药物诱导的心肌脂质改变研究
Nimalee Jayasekera,Nav Raj Phulara,Lloyd Wei Tat Tang et al.
Nimalee Jayasekera et al.
Clinically used drugs can adversely affect cardiac function. Doxorubicin (DOX), a chemotherapeutic drug, and efavirenz (EFV), an antiretroviral drug, are known to associate with adverse cardiovascular events and alterations of serum lipid p...
Molnupiravir is not a selective CES2 probe substrate: in vitro evidence for CES1 involvement [0.03%]
莫努匹拉韦不是CES2特异性探针底物：体外证据表明CES1参与其中
Luke Roberts,Hannah Moulton,Xiaofeng Wu et al.
Luke Roberts et al.
Molnupiravir is an orally administered prodrug that requires enzymatic hydrolysis to generate N-hydroxycytidine, a pharmacologically active ribonucleoside analog. Previous reports suggested that molnupiravir hydrolysis was selectively catal...
Neddylation inhibition sensitizes gastric cancer to 5-fluorouracil by targeting the post-translational stability of the metabolic enzyme dihydropyrimidine dehydrogenase [0.03%]
去 neddylation通过靶向代谢酶胸苷酸合成酶的翻译后稳定性使胃癌对氟尿嘧啶敏感化
Qianqian Zhang,Jingyi Hu,Yangbo Liu et al.
Qianqian Zhang et al.
The therapeutic efficacy of 5-fluorouracil (5-FU), a cornerstone of gastric cancer chemotherapy, is predominantly limited by its catabolic inactivation in tumors. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme responsible...
Pregnane X receptor, constitutive androstane receptor, or peroxisome proliferator-activated receptor α activation does not affect yes-associated protein phase separation under physiological and hyperosmotic conditions [0.03%]
pregnane X受体、组成型雄甾烷受体或过氧化物酶体增殖激活受体α的激活不会影响生理和高渗条件下的Yes相关蛋白相分离
Pengfei Zhao,Shicheng Fan,Yanying Zhou et al.
Pengfei Zhao et al.
Yes-associated protein (YAP) is a critical factor of the Hippo pathway, which plays a key role in regulating organ size. Pregnane X receptor (PXR), constitutive androstane receptor (CAR), and peroxisome proliferator-activated receptor α (P...
Impact of POR and cytochrome b5 variability on the genotype-phenotype discordance of CYP2A6 and CYP2D6: A quantitative analysis in Chinese human livers [0.03%]
POR和细胞色素b5的多态性对CYP2A6和CYP2D6基因型与表型不一致的影响：中国人肝脏中的定量分析
Yan Fang,Jiyao Wang,Demeng Liu et al.
Yan Fang et al.
Genotyping of CYP2A6 and CYP2D6 is a cornerstone of personalized medicine; however, current dosing algorithms often assume distinct phenotypic clusters, overlooking the substantial phenotypic overlap among genotypes. This study aimed to qua...
Plasma coproporphyrins for evaluating OATP1B and OATP2B1 activities: Coproporphyrin-III unsuitable as an OATP2B1 biomarker in Japanese general population [0.03%]
血浆粪卟啉用于评估OATP1B和OATP2B1活性：在普通日本人中不宜将粪卟啉-Ⅲ作为OATP2B1生物标志物
Jun Negami,Yosuke Suzuki,Teruhide Koyama et al.
Jun Negami et al.
Organic anion transporting polypeptides (OATP)1B1/1B3 are mainly expressed in the liver, whereas OATP2B1 is expressed in the liver as well as in the intestine. Coproporphyrin (CP)-I has been reported to be a highly sensitive biomarker for t...
Humanized-liver TK-NOG mice lacking plasma carboxylesterase 1c improve the prediction of human carboxylesterase 1-mediated drug metabolism [0.03%]
缺乏血浆羧酸酯酶1c的人类化肝脏TK-NOG小鼠改善了人类羧酸酯酶1介导的药物代谢预测能力
Shotaro Uehara,Yuichiro Higuchi,Nao Yoneda et al.
Shotaro Uehara et al.
Chimeric NOD/Shi-Scid IL2 receptor gamma-null mice expressing the HSVtk mutant 30 with humanized livers (humanized-liver mice) are valuable models for predicting drug metabolism in humans. However, carboxylesterase 1c (Ces1c) secreted from ...