Inhibition of Glucose Transporters and Glutaminase Synergistically Impairs Tumor Cell Growth [0.03%]
同时抑制葡萄糖转运蛋白和谷氨酰胺合成酶可协同抑制肿瘤细胞的生长
Elena S Reckzeh,George Karageorgis,Melanie Schwalfenberg et al.
Elena S Reckzeh et al.
Cancer cells sustain growth by altering their metabolism to accelerated aerobic glycolysis accompanied by increased glucose demand and employ glutamine as additional nutrient source. This metabolic adaptation induces upregulation of glucose...
Engineering Forward Genetics into Cultured Cancer Cells for Chemical Target Identification [0.03%]
工程遗传学在癌细胞培养中的应用及化学靶点鉴定
Juan Manuel Povedano,Joel Liou,David Wei et al.
Juan Manuel Povedano et al.
Target identification for biologically active small molecules remains a major barrier for drug discovery. Cancer cells exhibiting defective DNA mismatch repair (dMMR) have been used as a forward genetics system to uncover compound targets. ...
Discovery of a Novel DNA Gyrase-Targeting Antibiotic through the Chemical Perturbation of Streptomyces venezuelae Sporulation [0.03%]
通过化学干扰束状丛枝菌根放线菌孢子形成发现一类新型DNA回旋酶靶向抗生素
Scott McAuley,Alan Huynh,Alison Howells et al.
Scott McAuley et al.
Common approaches to antibiotic discovery include small-molecule screens for growth inhibition in target pathogens and screens for inhibitors of purified enzymes. These approaches have a shared intent of seeking to directly target a vital A...
Mechanistic MALDI-TOF Cell-Based Assay for the Discovery of Potent and Specific Fatty Acid Synthase Inhibitors [0.03%]
一种用于发现有效的乙酰辅酶A羧化酶抑制剂的MALDI-TOF机理细胞检测法
David Weigt,Cynthia A Parrish,Julie A Krueger et al.
David Weigt et al.
Human cancers require fatty acid synthase (FASN)-dependent de novo long-chain fatty acid synthesis for proliferation. FASN is therefore an attractive drug target, but fast technologies for reliable label-free cellular compound profiling are...
Divergent Polypharmacology-Driven Cellular Activity of Structurally Similar Multi-Kinase Inhibitors through Cumulative Effects on Individual Targets [0.03%]
结构类似多激酶抑制剂发散型多靶向活性通过针对单个靶点的累积效应产生细胞作用力
Natalia J Sumi,Claudia Ctortecka,Qianqian Hu et al.
Natalia J Sumi et al.
Despite recent successes of precision and immunotherapies there is a persisting need for novel targeted or multi-targeted approaches in complex diseases. Through a systems pharmacology approach, including phenotypic screening, chemical and ...
Analyzing Resistance to Design Selective Chemical Inhibitors for AAA Proteins [0.03%]
分析针对AAA蛋白的设计性化学抑制剂的抗性问题
Rudolf Pisa,Tommaso Cupido,Jonathan B Steinman et al.
Rudolf Pisa et al.
Drug-like inhibitors are often designed by mimicking cofactor or substrate interactions with enzymes. However, as active sites are comprised of conserved residues, it is difficult to identify the critical interactions needed to design selec...
Discovery of Druggable Host Factors Critical to Plasmodium Liver-Stage Infection [0.03%]
发现疟原虫肝期感染的药物靶点宿主因子
Rene Raphemot,Maria Toro-Moreno,Kuan-Yi Lu et al.
Rene Raphemot et al.
Plasmodium parasites undergo an obligatory and asymptomatic developmental stage within the liver before infecting red blood cells to cause malaria. The hijacked host pathways critical to parasite infection during this hepatic phase remain p...
Site-Selective Antibody Functionalization via Orthogonally Reactive Arginine and Lysine Residues [0.03%]
通过正交反应性精氨酸和赖氨酸残基进行位点选择性抗体功能化
Dobeen Hwang,Napon Nilchan,Alex R Nanna et al.
Dobeen Hwang et al.
Homogeneous antibody-drug conjugates (ADCs) that use a highly reactive buried lysine (Lys) residue embedded in a dual variable domain (DVD)-IgG1 format can be assembled with high precision and efficiency under mild conditions. Here we show ...
The Convergence of Stem Cell Technologies and Phenotypic Drug Discovery [0.03%]
干细胞技术与基于表型的药物发现间的汇聚点
Alexandra Friese,Andrei Ursu,Andreas Hochheimer et al.
Alexandra Friese et al.
Recent advances in induced pluripotent stem cell technologies and phenotypic screening shape the future of bioactive small-molecule discovery. In this review we analyze the impact of small-molecule phenotypic screens on drug discovery as we...
Discovery of Small-Molecule Selective mTORC1 Inhibitors via Direct Inhibition of Glucose Transporters [0.03%]
通过直接抑制葡萄糖转运蛋白发现雷帕霉素复合物1选择性小分子抑制剂
Seong A Kang,David J O&#x;Neill,Andreas W Machl et al.
Seong A Kang et al.
The mechanistic target of rapamycin (mTOR) is a central regulator of cellular metabolic processes. Dysregulation of this kinase complex can result in a variety of human diseases. Rapamycin and its analogs target mTORC1 directly; however, ch...