Two-step metabolic activation to ortho-benzoquinone intermediate and its role in 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside-induced liver injury in mice [0.03%]
两步代谢活化成邻苯醌中间体及其在诱导小鼠肝脏损伤中作用机制的研究
Hong Pan,Guohong Zhai,Qiuyi Jing et al.
Hong Pan et al.
2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) is the most abundant constituent of Polygonum multiflorum and is exclusively found in this herb. This renowned herbal medicine has been documented to lead to liver damage in humans. The...
Detection of antidrug antibodies against antibody-drug conjugates by solid-phase extraction with acid dissociation in cynomolgus monkey serum [0.03%]
通过固相提取酸 dissociation检测食蟹猴血清中药物抗体针对抗体药物偶联物的抗药抗体
Susan Chen,Konstantin Piatkov,Linlin Dong et al.
Susan Chen et al.
The formation of antidrug antibodies (ADAs) against antibody-drug conjugates (ADCs) can trigger a humoral immune response and change drug exposure. Although the immunogenicity assessment of an ADC drug in nonclinical nonhuman primates may n...
Identification of selective substrates and inhibitors of the major human renal uptake transporters [0.03%]
主要人类肾摄取转运蛋白的选择性底物和抑制剂的识别
Yik Pui Tsang,Acilegna G Rodriguez,Mark S Warren et al.
Yik Pui Tsang et al.
Renal clearance of drugs mediated by transporters can be affected by diseases (eg, inflammation due to infections), physiological changes (eg, pregnancy), or drug-drug interactions. To elucidate the transporters involved, the magnitude of e...
Structure-activity relationship of isoprenoid triazole bisphosphonate-based geranylgeranyl diphosphate synthase inhibitors: Effects on pharmacokinetics, biodistribution, and hepatic transporters [0.03%]
异戊二烯三氮唑双膦酸盐类牻牛儿牻牛儿基二磷酸合成酶抑制剂的构效关系：对药代动力学、生物分布和肝转运蛋白的影响
Staci L Haney,Yashpal S Chhonker,Mamunur Rashid et al.
Staci L Haney et al.
Geranylgeranyl diphosphate synthase produces the isoprenoid geranylgeranyl diphosphate, which is used in protein geranylgeranylation. Our previous work illustrates that geranylgeranyl diphosphate synthase inhibitors (GGSIs) disrupt Rab-medi...
In vitro metabolism of targeted covalent inhibitors and their thiol conjugates by gut microbiome from rats, mice, and humans [0.03%]
来自大鼠，小鼠和人类的肠道微生物对靶向共价抑制剂及其巯基偶联物的体外代谢研究
Ting-Jia Gu,Jingwei Cai,Alexis Auster et al.
Ting-Jia Gu et al.
Targeted covalent inhibitor (TCI) represents a noncanonical class of small molecules that function via "inactivating" the target protein through the formation of drug-protein adducts. The electrophilic groups (warheads) embedded in the TCIs...
Clearance prediction with three novel plated human hepatocyte models compared to conventional suspension assays: Assessment with 50 compounds and multiple donors [0.03%]
三种新型人肝细胞系模型与传统悬浮液检测的清除此消彼长预测：通过50种化合物和多个受试者评估
David A Kukla,Julia A Schulz Pauly,Paul R Lesniak et al.
David A Kukla et al.
Incubation of drugs with suspension hepatocytes (SH) to determine intrinsic clearance is common in drug discovery. However, the limited duration of SH assays hampers clearance assessment of metabolically stable compounds. In turn, this has ...
Development of an OATP1-humanized transchromosomic mouse model for prediction of hepatic drug uptake in humans [0.03%]
OATP1人源化转染色体小鼠模型的开发，用于预测人类肝脏药物摄取
Tomoki Koishikawa,Kanako Kazuki,Rina Ohnishi et al.
Tomoki Koishikawa et al.
Transchromosomic technology using mouse artificial chromosomes (MACs) offers a promising approach for transferring gene clusters into host organisms. This study focused on the multispecific organic anion-transporting polypeptides (OATPs) in...
Evaluation of reversible cytochrome P450 inhibition by Withania somnifera leaf and root extracts [0.03%]
Withania somnifera叶和根提取物对可逆的细胞色素P450抑制的评估
Zarna Raichura,Kabre Heck,Jaewoo Choi et al.
Zarna Raichura et al.
It is important to understand the potential of botanical-drug interactions to ensure the safe use of botanical dietary supplements (BDS). Cytochrome P450 (P450) is one of the most abundant phase 1 drug-metabolizing enzymes and is accountabl...
Rat PermQ: A permeability- and perfusion-based physiologically based pharmacokinetic model for improved prediction of drug concentration-time profiles in rat [0.03%]
_rat PermQ：一种基于渗透率和灌注的生理药代动力学模型，用于改善大鼠药物浓度-时间曲线的预测_
Yifan Gong,Ken Korzekwa,Swati Nagar
Yifan Gong
A new rat permeability- and perfusion-limited physiologically based pharmacokinetic model, "rat PermQ," was developed with the goal of improving concentration-time (C-t) predictions of drugs. Similar to the previously published human PermQ,...
Decreased expression of P-glycoprotein in the placenta of women with autoimmune disease [0.03%]
自身免疫性疾病妇女胎盘中P-糖蛋白的表达降低
Angela Pollinzi,Kamelia Mirdamadi,Navaz Karimian Pour et al.
Angela Pollinzi et al.
Autoimmune diseases (ADs), such as systemic lupus erythematosus (SLE), require multiple medications to ensure maternal-fetal health during pregnancy. These medications are often substrates for placental transporters that could cross over to...