Chlorcyclizine Inhibits Viral Fusion of Hepatitis C Virus Entry by Directly Targeting HCV Envelope Glycoprotein 1 [0.03%]
氯环嗪通过直接靶向HCV包膜糖蛋白1抑制丙型肝炎病毒的融合和进入病毒感染细胞的过程中枢置病毒生命周期中的关键事件。
Zongyi Hu,Adam Rolt,Xin Hu et al.
Zongyi Hu et al.
Chlorcyclizine (CCZ) is a potent hepatitis C virus (HCV) entry inhibitor, but its molecular mechanism is unknown. Here, we show that CCZ directly targets the fusion peptide of HCV E1 and interferes with the fusion process. Generation of CCZ...
Blockade of Oncogenic NOTCH1 with the SERCA Inhibitor CAD204520 in T Cell Acute Lymphoblastic Leukemia [0.03%]
钙离子ATP酶抑制剂CAD204通过阻断NOTCH1致癌信号治疗T细胞急性淋巴细胞白血病
Matteo Marchesini,Andrea Gherli,Anna Montanaro et al.
Matteo Marchesini et al.
The identification of SERCA (sarco/endoplasmic reticulum calcium ATPase) as a target for modulating gain-of-function NOTCH1 mutations in Notch-dependent cancers has spurred the development of this compound class for cancer therapeutics. Des...
Specific Knockdown of α-Synuclein by Peptide-Directed Proteasome Degradation Rescued Its Associated Neurotoxicity [0.03%]
肽导向的蛋白酶体降解特异性敲低α-突触核蛋白可缓解其相关神经毒性
Jing Qu,Xiaoxi Ren,Fenqin Xue et al.
Jing Qu et al.
α-Synuclein (α-syn) overload is strongly associated with Parkinson disease (PD), and reduction of the α-syn level by targeting the peptide-based system through the autophagy-lysosomal pathway (ALP) is a promising strategy to delay PD pro...
Inhibition of Resistance-Refractory P. falciparum Kinase PKG Delivers Prophylactic, Blood Stage, and Transmission-Blocking Antiplasmodial Activity [0.03%]
PKG蛋白酶活性抑制剂抗疟药物的研发及其作用机制研究
Manu Vanaerschot,James M Murithi,Charisse Flerida A Pasaje et al.
Manu Vanaerschot et al.
The search for antimalarial chemotypes with modes of action unrelated to existing drugs has intensified with the recent failure of first-line therapies across Southeast Asia. Here, we show that the trisubstituted imidazole MMV030084 potentl...
Plasmodium vivax Liver and Blood Stages Recruit the Druggable Host Membrane Channel Aquaporin-3 [0.03%]
间日疟原虫肝期和血症期劫持宿主Aquaporin-3通道蛋白的作用机制研究
Dora Posfai,Steven P Maher,Camille Roesch et al.
Dora Posfai et al.
Plasmodium vivax infects hepatocytes to form schizonts that cause blood infection, or dormant hypnozoites that can persist for months in the liver before leading to relapsing blood infections. The molecular processes that drive P. vivax sch...
Combined Omics Approach Identifies Gambogic Acid and Related Xanthones as Covalent Inhibitors of the Serine Palmitoyltransferase Complex [0.03%]
结合组学方法鉴定出 gambogic acid 及相关类黄酮作为丝氨酸 palmitoyltransferase 复合物共价抑制剂
Dominic G Hoch,Daniel Abegg,J Thomas Hannich et al.
Dominic G Hoch et al.
In this study, we identify the natural product gambogic acid as well as structurally related synthetic xanthones as first-in-class covalent inhibitors of the de novo sphingolipid biosynthesis. We apply chemoproteomics to determine that gamb...
Simultaneous Control of Endogenous and User-Defined Genetic Pathways Using Unique ecDHFR Pharmacological Chaperones [0.03%]
利用独特的ecDHFR药理学伴侣同时控制内源性和用户定义的基因通路
Prerana Ramadurgum,DaNae R Woodard,Steffi Daniel et al.
Prerana Ramadurgum et al.
Destabilizing domains (DDs), such as a mutated form of Escherichia coli dihydrofolate reductase (ecDHFR), confer instability and promote protein degradation. However, when combined with small-molecule stabilizers (e.g., the antibiotic trime...
Progress in Understanding Ferroptosis and Challenges in Its Targeting for Therapeutic Benefit [0.03%]
铁死亡研究进展及其作为治疗手段所面临的挑战
Yilong Zou,Stuart L Schreiber
Yilong Zou
Ferroptosis is an iron-dependent cell-death modality driven by oxidative phospholipid damage. In contrast to apoptosis, which enables organisms to eliminate targeted cells purposefully at specific times, ferroptosis appears to be a vulnerab...
Alexia Belavgeni,Claudia Meyer,Julian Stumpf et al.
Alexia Belavgeni et al.
In the last decade, the role of apoptosis in the pathophysiology of acute kidney injury (AKI) and AKI to chronic kidney disease (CKD) progression has been revisited as our understanding of ferroptosis and necroptosis has emerged. A growing ...
The Role of Chemical Biology in the Discovery and Understanding of Ferroptosis [0.03%]
化学生物学在铁死亡发现和作用机制研究中的重要作用
Mishtu Dey,Bridget Wagner
Mishtu Dey