Transformation of a Potent C9-Substituted Phenylmorphan into MOR Partial Agonists with Improvement of Metabolic Stability: An In Vitro, In Vivo, and In Silico Study [0.03%]
一项关于μ受体偏激动剂的体内、体外和计算研究：C9位取代的苯吗喃类衍生物的设计及代谢稳定性优化
Delmis E Hernandez,Dan Luo,Thomas E Prisinzano et al.
Delmis E Hernandez et al.
Replacement of the phenolic hydroxy in 3-((1R,5S,9R)-2-phenethyl-9-vinyl-2-azabicyclo[3.3.1]nonan-5-yl)phenol (DC-1-76.2), a potent efficacious MOR agonist, with an amide bioisosteric moiety provided a MOR partial agonist with morphine-like...
Pharmacological Regulation of Heat Shock Response via Aptamer-Antidote Couple [0.03%]
基于适配体-解毒剂对的热休克反应药物调控研究
Jaskirat Kaur,Ipsita Roy
Jaskirat Kaur
Heat shock factor 1 (HSF1) orchestrates the cellular heat shock response (HSR) by binding to heat shock elements (HSEs) in the promoters of genes encoding heat shock proteins (HSPs). In a nonstressed state, HSF1 exists in a dormant complex ...
Mass-Spectrometry-Based GEE Footprinting Characterizes Kinetic Mechanisms and Sites of Conformational Change in Amyloid β 1-42 Aggregation [0.03%]
基于质谱的GEE脚印表征技术揭示了淀粉样蛋白β 1-42聚集的动力学机制和构象变化位点
Xinyi Cynthia Kuang,Don L Rempel,Yanchun Lin et al.
Xinyi Cynthia Kuang et al.
Understanding the dynamics of Aβ aggregation is critical for elucidating Alzheimer's disease (AD) progression. This study extends our previous work on Aβ42 using fast photochemical oxidation of proteins (FPOP) and pulsed hydrogen-deuteriu...
Thioflavin T Lasing Probe for Mucin Detection in Simulated Tears as a Targeting Strategy for Brain Tumors [0.03%]
硫黄素T激光探针在模拟泪液中检测黏蛋白作为脑瘤靶向策略的目标检测方法研究
Ewelina Jalonicka,Konstantin Rusakov,Grzegorz Szwachta et al.
Ewelina Jalonicka et al.
A novel optical approach for a noninvasive detection of mucins in tear fluid is proposed, aiming at the early diagnosis of brain tumors such as glioblastoma. Utilizing Thioflavin T (ThT) as a fluorescent probe, our study demonstrates that T...
Identification of a Lipid-Exposed Extrahelical Binding Site for Positive Allosteric Modulators of the Dopamine D2 Receptor [0.03%]
多巴胺D2受体阳性变构调节剂的外螺旋表露结合位点的鉴定
Herman D Lim,Damian Bartuzi,Alastair C Keen et al.
Herman D Lim et al.
Recently, the first small-molecule positive allosteric modulators (PAMs) of the dopamine D2 receptor (D2R) were identified. The more potent PAM potentiated the effects of D2R signaling in vitro and in an in vivo model predictive of anti-Par...
Adverse Outcome Pathway and Machine Learning to Predict Drug Induced Seizure Liability [0.03%]
用于预测药物诱发癫痫倾向的不良结果途径和机器学习方法
Thomas R Lane,Scott H Snyder,Joshua S Harris et al.
Thomas R Lane et al.
Central nervous system (CNS) drugs have the highest clinical attrition, often due to CNS-related toxicities such as drug-induced seizures (DIS). Early prediction of DIS risk could reduce failure rates and optimize drug development by priori...
Yahong Qiu,Lixia Zhu,Wenyan Cai et al.
Yahong Qiu et al.
Depression is a potentially life-threatening psychiatric disorder that affects the physical and mental health of millions of individuals worldwide. It can manifest at any stage of life, inducing profound emotional despondency, negative cogn...
Promoting Secretion of Pathological Tau Species Using an Induced Proximity Platform That Engages the Autophagy Pathway [0.03%]
利用自噬途径诱导邻近平台促进病理性Tau蛋白分泌
Yekaterina Kovalyova,Cesar De Leon,Alicja Krasowska-Zoladek et al.
Yekaterina Kovalyova et al.
Intracellular accumulation of aberrantly phosphorylated aggregated tau protein can contribute to neuronal dysfunction associated with many neurodegenerative diseases. Thus, removing such tau species is an attractive therapeutic hypothesis f...
Allopregnanolone Regulation of Phasic Dopamine Release and Motivated Behavior [0.03%]
孕酮衍生物allopregnanolone对阶段性多巴胺释放和动机行为的调节作用
Minna H McFarland,A Leslie Morrow,Donita L Robinson
Minna H McFarland
Allopregnanolone, an endogenous neurosteroid that is a potent, positive allosteric modulator of γ-aminobutyric acid type A (GABAA) receptors, has emerged as a compound with considerable potential in the treatment of psychiatric disorders, ...
The Vicious Consequences of Chronic Kidney Disease on Cognitive Impairment and Alzheimer's Disease [0.03%]
慢性肾脏疾病对认知障碍和阿尔茨海默病的恶劣影响
Abhideep Roy,Rubina Roy,Pallab Bhattacharya et al.
Abhideep Roy et al.
Chronic kidney disease (CKD) and Alzheimer's disease (AD) are two prevalent and debilitating conditions that frequently coexist, with CKD contributing to cognitive decline and potentially exacerbating AD pathology. In CKD, irreversible chan...