Building structure activity relationships (SAR) to avoid toxicity due to unwanted CNS ion channel activity [0.03%]
建立结构活性关系（SAR），以避免由于不必要的中枢神经系统离子通道活性而导致的毒性
Louisa A K Zolkiewski,Kimberly L Rockley,Ruth A Roberts et al.
Louisa A K Zolkiewski et al.
We previously described an integrated in vitro liability assay for seizure, a new approach methodology (NAM) to reduce toxicity due to central nervous system (CNS) liability in drug discovery and development. Here we report the development ...
Towards Bayesian-based quantitative adverse outcome pathways using in vitro data from open literature and continuous variables: a case example for liver fibrosis [0.03%]
基于Bayesian的定量不良结果途径向利用开放文献中的体外数据及连续变量发展的一个肝纤维化案例示例
Robin Durnik,Tereza Juchelkova,Helge Hecht et al.
Robin Durnik et al.
As toxicology shifts towards non-animal testing, quantitative models are essential to predict adverse health effects from molecular or cellular perturbations. Quantitative Adverse Outcome Pathways (qAOPs) represent such models, building on ...
Mitochondrial Dysfunction, Cerebral Metabolic Crisis, and Exploratory Bioenergetic Biomarkers in a Translational Swine Model of Acute Carbon Monoxide Poisoning [0.03%]
急性一氧化碳中毒的线粒体功能障碍、脑代谢危机及探索性生物能量标志物的转化猪模型研究
Abigail Insana,Alistair Lewis,John C Greenwood et al.
Abigail Insana et al.
Carbon monoxide (CO) poisoning remains a major cause of toxicologic morbidity and mortality and is a leading cause of acute neurologic injury among poisoned patients, yet the mechanisms underlying cerebral bioenergetic dysfunction remain in...
Integrating Mechanistic Data to Contextualize in Vivo Apical Observations Using the Developmental Neurotoxicity in Vitro Battery [0.03%]
利用发育神经毒性体外检测平台整合机制数据以阐释体内观察结果
Brianna L Jackson,Yaoxing Wu,Kian Afsharian et al.
Brianna L Jackson et al.
Regulatory toxicity studies traditionally rely on in vivo apical endpoints for hazard characterization and risk assessment; when available, relevant and reliable in vitro assays are anticipated to aid this interpretation. Developmental neur...
Ethylene Glycol Monomethyl Ether Altered Rat Sperm Small RNAs with Critical Developmental Roles [0.03%]
乙二醇单甲醚对大鼠精子携带发育关键功能微小RNA的影响
Yuan Pu,August Guang,Xinran Qi et al.
Yuan Pu et al.
Ethylene glycol monomethyl ether (EGME) is a testicular germ cell toxicant that selectively targets spermatocytes. In rats, male-only EGME exposure reduces mating success and can lead to an increase in resorbed fetuses. In a previous study,...
Hepatic Responses as Potential Biomarkers of Idiosyncratic Drug Reaction Risk [0.03%]
肝反应作为潜在的特异质性药物不良反应生物标志物研究
Jiamin Liao,Xiaotian Lyu,Kristy Yang et al.
Jiamin Liao et al.
Idiosyncratic drug reactions (IDRs) and, in particular, idiosyncratic drug-induced liver injury (iDILI) represent a significant risk for drug development. There are multiple lines of evidence that such reactions are mediated by the adaptive...
Systematic comparison of temporal hepatotoxicant-induced gene network responses across three liver test systems [0.03%]
基于三种肝脏检测模型比较毒物诱导的基因网络反应
Tamara Y Danilyuk,Marou Schouten,Elsje J Burgers et al.
Tamara Y Danilyuk et al.
Drug-induced liver injury (DILI) arises from dynamic and time-dependent cellular stress responses that remain insufficiently captured by conventional single-timepoint toxicogenomic assessments. We systematically characterized temporal and c...
Investigation of a Metabolism-Dependent Aryl Hydrocarbon Receptor (AhR) Off-Target Activation for a Drug Development Candidate and a Screening Strategy for De-Risking Backups [0.03%]
一种药物研发候选化合物的代谢活化非靶点芳香烃受体（AhR）激活作用的调查及降低备选药物风险的筛选策略研究
Amy G Aslamkhan,Wen Kang,Karin Otte et al.
Amy G Aslamkhan et al.
During lead optimization, off-target activation of the aryl hydrocarbon receptor (AhR) was identified for Compound 25. AhR is a xenobiotic-responsive transcription factor associated with adverse outcomes in rodents (and potentially humans) ...