Pharmacogenomics of Chemically Distinct Classes of Keap1-Nrf2 Activators Identify Common and Unique Gene, Protein, and Pathway Responses In Vivo [0.03%]
化学结构不同的Keap1-Nrf2激活剂的药物基因组学鉴定出体内共同和独特的基因、蛋白质及途径反应
Ryan S Wible,Quynh T Tran,Samreen Fathima et al.
Ryan S Wible et al.
The Kelch-like erythroid-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2) signaling pathway is the subject of several clinical trials evaluating the effects of Nrf2 activation on the prevention of cancer and diabetes and the treat...
Identifying Functional Hotspot Residues for Biased Ligand Design in G-Protein-Coupled Receptors [0.03%]
G蛋白偶联受体功能热点残基的识别用于偏置配体设计
Anita K Nivedha,Christofer S Tautermann,Supriyo Bhattacharya et al.
Anita K Nivedha et al.
G-protein-coupled receptors (GPCRs) mediate multiple signaling pathways in the cell, depending on the agonist that activates the receptor and multiple cellular factors. Agonists that show higher potency to specific signaling pathways over o...
Elucidation of the Binding Mode of the Carboxyterminal Region of Peptide YY to the Human Y2 Receptor [0.03%]
人Y2受体与肽酪氨素YY羧端区域结合模式的阐明
Bo Xu,Silvana Vasile,Søren Østergaard et al.
Bo Xu et al.
Understanding the agonist-receptor interactions in the neuropeptide Y (NPY)/peptide YY (PYY) signaling system is fundamental for the design of novel modulators of appetite regulation. We report here the results of a multidisciplinary approa...
Probing the Mechanism of Receptor Activity-Modifying Protein Modulation of GPCR Ligand Selectivity through Rational Design of Potent Adrenomedullin and Calcitonin Gene-Related Peptide Antagonists [0.03%]
通过合理设计肾上腺髓质素和降钙素基因相关肽拮抗剂探究受体活性调节蛋白对GPCR配体选择性的作用机制
Jason M Booe,Margaret L Warner,Amanda M Roehrkasse et al.
Jason M Booe et al.
Binding of the vasodilator peptides adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) to the class B G protein-coupled receptor calcitonin receptor-like receptor (CLR) is modulated by receptor activity-modifying proteins (RAMPs...
Sustained Formation of Nitroglycerin-Derived Nitric Oxide by Aldehyde Dehydrogenase-2 in Vascular Smooth Muscle without Added Reductants: Implications for the Development of Nitrate Tolerance [0.03%]
醛脱氢酶2介导的血管平滑肌中无供电子剂的硝酸甘油衍生物型一氧化氮持续生成：对硝酸盐耐药性发展的意义
Marissa Opelt,Gerald Wölkart,Emrah Eroglu et al.
Marissa Opelt et al.
According to current views, oxidation of aldehyde dehydrogenase-2 (ALDH2) during glyceryltrinitrate (GTN) biotransformation is essentially involved in vascular nitrate tolerance and explains the dependence of this reaction on added thiols. ...
Jan M Schilling,Brian P Head,Hemal H Patel
Jan M Schilling
Caveolins have been recognized over the past few decades as key regulators of cell physiology. They are ubiquitously expressed and regulate a number of processes that ultimately impact efficiency of cellular processes. Though not critical t...
Activation of Constitutive Androstane Receptor Ameliorates Renal Ischemia-Reperfusion-Induced Kidney and Liver Injury [0.03%]
constitutive androstane receptor激活缓解肾脏缺血再灌注损伤诱导的肝肾损害
You-Jin Choi,Dong Zhou,Anne Caroline S Barbosa et al.
You-Jin Choi et al.
Acute kidney injury (AKI) is associate with high mortality. Despite evidence of AKI-induced distant organ injury, a relationship between AKI and liver injury has not been clearly established. The goal of this study is to investigate whether...
Inhibitory Effects of Endogenous Linoleic Acid and Glutaric Acid on the Renal Glucuronidation of Berberrubine in Mice and on Recombinant Human UGT1A7, 1A8, and 1A9 [0.03%]
内源性亚油酸和谷氨酸对小鼠肾药葡萄糖醛酸转移酶的作用及对人UGT1A7、1A8和1A9重组酶的作用
Na Yang,Sijia Li,Caixia Yan et al.
Na Yang et al.
Berberrubine (BRB) has a strong lipid-lowering effect and can be extensively metabolized into berberrubine-9-O-β-d-glucuronide (BRBG) in vivo. Recently, pharmacokinetics studies showed that the production of BRBG was significantly decrease...
Terry Kenakin
Terry Kenakin
The question of whether signaling bias is a viable discovery strategy for drug therapy is discussed as a value proposition. On the positive side, bias is easily identified and quantified in simple in vitro functional assays with little reso...
Molecular Mechanisms of Biased and Probe-Dependent Signaling at CXC-Motif Chemokine Receptor CXCR3 Induced by Negative Allosteric Modulators [0.03%]
CXC基序趋化因子受体CXCR3的负向变构调节剂诱导的选择性及探针依赖性信号转导机制分子研究
Regine Brox,Lampros Milanos,Noureldin Saleh et al.
Regine Brox et al.
Our recent explorations of allosteric modulators with improved properties resulted in the identification of two biased negative allosteric modulators, BD103 (N-1-{[3-(4-ethoxyphenyl)-4-oxo-3,4-dihydropyrido[2,3-d]pyrimi-din2yl]ethyl}-4-(4-f...