Development and validation of LC-MS-based bioanalytical methods for oligonucleotide therapeutics: points to consider [0.03%]
用于寡核苷酸药物的LC-MS基生物分析方法的开发和验证：注意事项要点考虑因素
Yuchen Sun,Kosuke Saito,Shin-Ichiro Nitta et al.
Yuchen Sun et al.
The analysis of oligonucleotide therapeutics, including antisense oligonucleotides and siRNAs, using existing bioanalytical methods presents unique analytical challenges owing to their distinctive physicochemical properties. Although the IC...
Characterization of unusual pyrazole ring-rearranged metabolites of DS-1971a specific to monkeys [0.03%]
特异猴类DS-1971a药物的吡唑环重排代谢物的表征
Daigo Asano,Kazuyoshi Michiba,Kayoko Masuda et al.
Daigo Asano et al.
We previously reported that various metabolites were detected in mice, monkeys, and humans after oral administration of radiolabeled DS-1971a. Among these metabolites, mono- (M6) and di-oxidized (M12 and M13) forms were recognized as being ...
A novel scaling approach for human pharmacokinetic prediction of antibody-drug conjugates using minimal nonclinical data: Integration of monkey PK and in vitro data [0.03%]
一种新颖的抗体药物偶联物人类药代动力学预测缩放方法：基于最少非临床数据的猴PK和体外数据分析整合
Satoshi Nakayama,Nao Torimoto,Toshiyuki Kudo et al.
Satoshi Nakayama et al.
Antibody-drug conjugates (ADCs) have emerged as promising cancer therapeutics; however, predicting their pharmacokinetics (PK) in humans remains challenging, particularly during early development. Therefore, we aimed to develop a practical ...
Role of the arachnoid mater organic anion and cation transporters in the clearance of prostaglandin D2 and metformin from the cerebrospinal fluid in rats [0.03%]
小鼠蛛网膜有机阴离子和阳离子转运蛋白在脑脊液清除前列腺素D2和双胍类药物中的作用
Yuka Yaguchi,Kazunari Sasaki,Mai Inagaki et al.
Yuka Yaguchi et al.
The arachnoid mater-forming cells, which exhibit expressions of organic anion and cation transporters, as well as tight junction proteins, form the blood-arachnoid barrier. The purpose of the present study was to clarify the roles of the ar...
Application of HepaSH cells for predicting cholestatic drug-induced liver injury via bile acid-dependent toxicity assay [0.03%]
HepaSH细胞在胆汁酸依赖型毒性试验中的应用预测药物性肝损伤中的胆汁淤积性损伤
Akinori Takemura,Shunya Naito,Yuichiro Higuchi et al.
Akinori Takemura et al.
Cholestatic liver injury is primarily caused by the accumulation of bile acids (BA) in hepatocytes. Based on this mechanism, an in vitro evaluation system for BA-dependent toxicity (BAtox) has been previously developed, using cryopreserved ...
A permeability assay adapted for the assessment of very poorly permeable compounds in the bRo5 space [0.03%]
一种适应于评估bRo5空间内通透性极差的化合物的渗透性测定法
Paulina Page,Dallas Bednarczyk
Paulina Page
Poorly permeable compounds in the beyond rule of 5 (bRo5) space often demonstrate acceptor well concentrations below the lower limit of quantification or limited resolution between apparent permeability (Papp) values. To address the accepto...
Microfluidic post-insertion preparation and evaluation of RGD- and PEG-modified macrophage-derived small extracellular vesicles [0.03%]
RGD和PEG修饰的巨噬细胞源外泌小胞的微流控柱后处理及评价研究
Mizuki Umino,Longjian Geng,Yusuke Ushiroda et al.
Mizuki Umino et al.
Various functionalization methods have been explored to enhance the targeted delivery of small extracellular vesicles (sEVs). We recently developed a microfluidic post-insertion method that enables the simultaneous incorporation of polyethy...
Differences in reactive metabolite formation and cytochrome P450 binding between acetaminophen and its bicyclo[1.1.1]pentane bioisostere [0.03%]
N-乙酰基-p-苯酚亚胺
Minami Shibata,Ayato Mizuno,Tomoki Nakayoshi et al.
Minami Shibata et al.
Bicyclo[1.1.1]pentane (BCP) is widely used as a bioisostere of 1,4-disubstituted benzene to prevent oxidative metabolism of the benzene ring by cytochrome P450s (P450s). In this study, we investigated its effectiveness in reducing metabolis...
Regulatory impact of G-quadruplexes in the human carboxylesterase 2 gene on drug and lipid metabolism [0.03%]
人羧酸酯酶2基因中G-四链体对药物和脂质代谢的调节作用的影响
Shintaro Kuroda,Shimon Nakashima,Seiya Takemoto et al.
Shintaro Kuroda et al.
G-Quadruplexes (G4s) are non-canonical DNA structures formed in guanine-rich sequences and recognized as crucial regulators of gene expression. We identified potential G4-forming sequences within the 5'-flanking region of the human carboxyl...
K2-EDTA anticoagulant suppresses calcium-dependent paraoxonase 1-mediated hydrolysis in human plasma stability assays [0.03%]
乙二胺四乙酸钾抗凝剂可抑制人血浆稳定性测定中的钙依赖型paraoxonase 1介导的水解反应
Lloyd Wei Tat Tang
Lloyd Wei Tat Tang
Plasma stability assays are routinely applied in early drug discovery to evaluate enzymatic liability and to support lead optimization efforts. Although these assays are generally regarded as robust, the extent to which pre-analytical varia...