Identification of Novel Metabolites of Vildagliptin in Rats: Thiazoline-Containing Thiol Adducts Formed via Cysteine or Glutathione Conjugation [0.03%]
达格列净在大鼠体内代谢生成含硫醇加合物（噻唑啉衍生物）的新代谢产物：半胱氨酸或谷胱甘肽结合的途径
Katsuhiko Mizuno,Kenji Takeuchi,Ken Umehara et al.
Katsuhiko Mizuno et al.
Vildagliptin (VG), a dipeptidyl peptidase-4 inhibitor, is used for treating type 2 diabetes. On rare occasions, VG causes liver injury as an adverse reaction. One case report suggested the involvement of immune responses in the hepatotoxici...
Enhanced Platelet Response to Clopidogrel in Zucker Diabetic Fatty Rats due to Impaired Clopidogrel Inactivation by Carboxylesterase 1 and Increased Exposure to Active Metabolite [0.03%]
由于羧酸酯酶1对氯吡格雷失活作用减弱和活性代谢产物暴露增加所致的Clarinelli大鼠血小板对氯吡格雷反应性增强
Hongwei Yao,Ruifeng Bai,Tianming Ren et al.
Hongwei Yao et al.
Clopidogrel (Clop), a thienopyridine antiplatelet prodrug, is metabolized by cytochrome P450s (CYPs) to an active metabolite, Clop-AM, and hydrolyzed by carboxylesterase (CES)1 to the inactive Clop-acid. Patients with type 2 diabetes (T2DM)...
Catalytic Cleavage of Disulfide Bonds in Small Molecules and Linkers of Antibody-Drug Conjugates [0.03%]
抗体偶联药物连接子和小分子中二硫键的催化断裂
Donglu Zhang,Aimee Fourie-O&#x;Donohue,Peter S Dragovich et al.
Donglu Zhang et al.
In cells, catalytic disulfide cleavage is an essential mechanism in protein folding and synthesis. However, detailed enzymatic catalytic mechanism relating cleavage of disulfide bonds in xenobiotics is not well understood. This study report...
The Regional-Specific Relative and Absolute Expression of Gut Transporters in Adult Caucasians: A Meta-Analysis [0.03%]
成人高加索人结肠不同区域转运体的相对和绝对表达：一项荟萃分析
Matthew D Harwood,Mian Zhang,Shriram M Pathak et al.
Matthew D Harwood et al.
The aim of this study was to derive region-specific transporter expression data suitable for in vitro-to-in vivo extrapolation (IVIVE) within a physiologically based pharmacokinetic (PBPK) modeling framework. A meta-analysis was performed w...
Carboxylesterase 2 and Intestine Transporters Contribute to the Low Bioavailability of Allisartan, a Prodrug of Exp3174 for Hypertension Treatment in Humans [0.03%]
人类降压药EXP3174前药阿利沙坦的低生物利用度是卡盒酯酶2和肠道转运蛋白共同作用的结果
Xiuli Li,Jingchao Sun,Zitao Guo et al.
Xiuli Li et al.
Exp3174 is an active metabolite of losartan for the treatment of hypertension. Allisartan (ALS3) is a marketed ester prodrug of Exp3174 to reduce bioavailability variation of losartan in China. However, ALS3 exhibited a lower oral absorptio...
Carfilzomib Is Not an Appropriate Payload of Antibody-Drug Conjugates Due to Rapid Inactivation by Lysosomal Enzymes [0.03%]
卡非佐米不适合用作抗体药物偶联物的载荷 因为其会被溶酶体酶迅速失活
Yong Ma,Josefa Dela Cruz-Chuh,S Cyrus Khojasteh et al.
Yong Ma et al.
Carfilzomib (CFZ) is a proteasome inhibitor used for oncology indications including treating multiple myeloma. CFZ is a potent cytotoxic agent with an IC50 value in the nanomolar range in various cancer cell lines and was considered as a po...
A Systematic In Vitro Investigation of the Inhibitor Preincubation Effect on Multiple Classes of Clinically Relevant Transporters [0.03%]
临床相关转运蛋白多种类别中的抑制前处理效应的系统体外研究
Péter Tátrai,Patrick Schweigler,Birk Poller et al.
Péter Tátrai et al.
Preincubation of a drug transporter with its inhibitor in a cell-based assay may result in the apparent enhancement of the inhibitory potency. Currently, limited data are available on potentiation of transporter inhibition by preincubation ...
Interactions of Alectinib with Human ATP-Binding Cassette Drug Efflux Transporters and Cytochrome P450 Biotransformation Enzymes: Effect on Pharmacokinetic Multidrug Resistance [0.03%]
Alectinib与人类ATP结合盒药物外排转运体和细胞色素P450代谢酶的相互作用及其对药动学多药耐药性的影响
Jakub Hofman,Ales Sorf,Dimitrios Vagiannis et al.
Jakub Hofman et al.
Alectinib is a tyrosine kinase inhibitor currently used as a first-line treatment of anaplastic lymphoma kinase-positive metastatic nonsmall cell lung cancer (NSCLC). In the present work, we investigated possible interactions of this novel ...
Coexpression of ABCB1 and ABCG2 in a Cell Line Model Reveals Both Independent and Additive Transporter Function [0.03%]
ABCB1和ABCG2在细胞系模型中的共表达揭示了独立的和附加的转运功能
Andrea N Robinson,Bethelihem G Tebase,Sonia C Francone et al.
Andrea N Robinson et al.
Although overexpression of multiple ATP-binding cassette transporters has been reported in clinical samples, few studies have examined how coexpression of multiple transporters affected resistance to chemotherapeutic drugs. We therefore exa...
Quantifying Hepatic Enzyme Kinetics of (-)-∆9-Tetrahydrocannabinol (THC) and Its Psychoactive Metabolite, 11-OH-THC, through In Vitro Modeling [0.03%]
通过体外建模定量(-)-Δ9-四氢大麻酚(THC)及其精神活性代谢物11-OH-THC的肝酶动力学参数
Gabriela I Patilea-Vrana,Jashvant D Unadkat
Gabriela I Patilea-Vrana
The prevalence of cannabis use and the concentrations of the psychoactive cannabinoid in cannabis, (-)-∆9-tetrahydrocannabinol (THC), are rising. Physiologically based pharmacokinetic modeling and simulations (PBPK M&S) can mechanistically...