Precision Retargeting: A Selective Covalent Inhibitor Illuminates CDK7 Biology [0.03%]
精准重定位：一个选择性的共价抑制剂揭示CDK7生物学特性
Lyn H Jones
Lyn H Jones
In this issue of Cell Chemical Biology, Olson et al. (2019) develop the first selective CDK7 irreversible inhibitor. Elegant cell-based studies using a CDK7 mutant that is not covalently engaged by the probe helped decipher the effects of i...
6-Phosphogluconate Dehydrogenase Links Cytosolic Carbohydrate Metabolism to Protein Secretion via Modulation of Glutathione Levels [0.03%]
6-磷酸葡萄糖酸脱氢酶通过调节谷胱甘肽水平将细胞溶质碳水化合物代谢与蛋白质分泌联系起来
Haoxin Li,Maria Ericsson,Bokang Rabasha et al.
Haoxin Li et al.
The proteinaceous extracellular matrix (ECM) is vital for the survival, proliferation, migration, and differentiation of many types of cancer. However, little is known regarding metabolic pathways required for ECM secretion. By using an unb...
Toxic Activation of an AAA+ Protease by the Antibacterial Drug Cyclomarin A [0.03%]
环素菌素A通过活化一个细菌蛋白酶从而发挥抗菌作用
Michael Maurer,Daniela Linder,Kamila B Franke et al.
Michael Maurer et al.
ATP-driven bacterial AAA+ proteases have been recognized as drug targets. They possess an AAA+ protein (e.g., ClpC), which threads substrate proteins into an associated peptidase (e.g., ClpP). ATPase activity and substrate selection of AAA+...
Quinoline Derivatives Kill Mycobacterium tuberculosis by Activating Glutamate Kinase [0.03%]
咔啉衍生物通过激活谷氨酸激酶杀灭结核杆菌
Gaelle G Makafe,Muzammal Hussain,Goverdhan Surineni et al.
Gaelle G Makafe et al.
There is a great need for identification and development of new anti-tuberculosis drugs with novel targets. Recent drug-discovery efforts typically focus on identifying inhibitors but not activators that perturb metabolic enzymes' functions...
A Systems Pharmacology Approach Uncovers Wogonoside as an Angiogenesis Inhibitor of Triple-Negative Breast Cancer by Targeting Hedgehog Signaling [0.03%]
基于系统药理学的黄酮 glucoside通过作用于Hh信号通路抑制三阴性乳腺癌血管生成
Yujie Huang,Jiansong Fang,Weiqiang Lu et al.
Yujie Huang et al.
Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous disease that lacks clinically actionable genetic alterations that limit targeted therapies. Here we explore a systems pharmacology approach that integrates drug-target ...
Multiomics Profiling Establishes the Polypharmacology of FDA-Approved CDK4/6 Inhibitors and the Potential for Differential Clinical Activity [0.03%]
多组学谱分析确定了美国食品药品监督管理局批准的CDK4/6抑制剂的多种药物作用机制及其不同的临床活性潜力
Marc Hafner,Caitlin E Mills,Kartik Subramanian et al.
Marc Hafner et al.
The target profiles of many drugs are established early in their development and are not systematically revisited at the time of FDA approval. Thus, it is often unclear whether therapeutics with the same nominal targets but different chemic...
Binding between G Quadruplexes at the Homodimer Interface of the Corn RNA Aptamer Strongly Activates Thioflavin T Fluorescence [0.03%]
玉米RNA适配体同二聚体界面的G四联体相互作用强烈激活硫黄素T荧光
Ljiljana Sjekloća,Adrian R Ferré-D&#x;Amaré
Ljiljana Sjekloća
Thioflavin T (ThT) is widely used for the detection of amyloids. Many unrelated DNAs and RNAs that contain G-quadruplex motifs also bind ThT and strongly activate its fluorescence. To elucidate the structural basis of ThT binding to G quadr...
Small-Molecule-Targeting Hairpin Loop of hTERT Promoter G-Quadruplex Induces Cancer Cell Death [0.03%]
小分子诱导的端粒酶倒重复序列G四链体结构变化引起肿瘤细胞凋亡
Jin H Song,Hyun-Jin Kang,Libia A Luevano et al.
Jin H Song et al.
Increased telomerase activity is associated with malignancy and poor prognosis in human cancer, but the development of targeted agents has not yet provided clinical benefit. Here we report that, instead of targeting the telomerase enzyme di...
The Natural Product Butylcycloheptyl Prodiginine Binds Pre-miR-21, Inhibits Dicer-Mediated Processing of Pre-miR-21, and Blocks Cellular Proliferation [0.03%]
天然产物正丁基环庚基prodiginine结合于pre-miR-21，抑制Dicer介导的加工及细胞增殖
Joe S Matarlo,Lauren R H Krumpe,William F Heinz et al.
Joe S Matarlo et al.
Identification of RNA-interacting pharmacophores could provide chemical probes and, potentially, small molecules for RNA-based therapeutics. Using a high-throughput differential scanning fluorimetry assay, we identified small-molecule natur...
Synthesis and Characterization of Specific Reverse Transcriptase Inhibitors for Mammalian LINE-1 Retrotransposons [0.03%]
用于哺乳动物LINE-1逆转录转座子的特异性逆转录酶抑制剂的设计、合成及表征
Guillermo Banuelos-Sanchez,Laura Sanchez,Maria Benitez-Guijarro et al.
Guillermo Banuelos-Sanchez et al.
Retrotransposons are a type of transposable element (TE) that have amplified to astonishing numbers in mammalian genomes, comprising more than a third of the human and mouse genomes. Long interspersed element class 1 (LINE-1 or L1) retrotra...