Structure-kinetic relationship reveals the mechanism of selectivity of FAK inhibitors over PYK2 [0.03%]
结构-动力学关系揭示了FAK抑制剂选择性区别于PYK2的机制
Benedict-Tilman Berger,Marta Amaral,Daria B Kokh et al.
Benedict-Tilman Berger et al.
There is increasing evidence of a significant correlation between prolonged drug-target residence time and increased drug efficacy. Here, we report a structural rationale for kinetic selectivity between two closely related kinases: focal ad...
Development of a potent and selective chemical probe for the pleiotropic kinase CK2 [0.03%]
一种有效的多功能蛋白激酶CK2的化学探针的研究开发
Carrow I Wells,David H Drewry,Julie E Pickett et al.
Carrow I Wells et al.
Building on the pyrazolopyrimidine CK2 (casein kinase 2) inhibitor scaffold, we designed a small targeted library. Through comprehensive evaluation of inhibitor selectivity, we identified inhibitor 24 (SGC-CK2-1) as a highly potent and cell...
Nailing Down a Notoriously Elusive Cancer Target: Direct Inhibition of MYC by a Covalent Small Molecule [0.03%]
攻克 elusive 癌症靶点的MYC蛋白：共价小分子直接抑制MYC蛋白功能
Matthew J Henley,Shelby K Doyle,Angela N Koehler
Matthew J Henley
Direct inhibition of the transcription factor MYC is widely recognized as one of the thorniest challenges in cancer drug discovery. In this issue of Cell Chemical Biology, Boike et al. (2020) discover a covalent MYC inhibitor that selective...
Formation of an aminovinyl-cysteine residue in thioviridamides occurs through a path independent of known lanthionine synthetase activity [0.03%]
硫抗生素噻沃爾idine的氨基乙烯半胱氨酸残基形成过程独立于已知的lanthionine合成酶活性
Yanping Qiu,Jingyu Liu,Yuqing Li et al.
Yanping Qiu et al.
2-Aminovinyl-cysteine (AviCys) is a thioether amino acid shared by a variety of ribosomally synthesized and posttranslationally modified peptides (RiPPs). Based on investigations into the biosynthesis of thioviridamide RiPPs in Streptomyces...
Designed PKC-targeting bryostatin analogs modulate innate immunity and neuroinflammation [0.03%]
设计出靶向PKC的派莫司类似物以调节先天免疫和神经炎症反应
Efrat Abramson,Clayton Hardman,Akira J Shimizu et al.
Efrat Abramson et al.
Neuroinflammation characterizes multiple neurologic diseases, including primary inflammatory conditions such as multiple sclerosis and classical neurodegenerative diseases. Aberrant activation of the innate immune system contributes to dise...
Profiling of MicroRNA Targets Using Activity-Based Protein Profiling: Linking Enzyme Activity to MicroRNA-185 Function [0.03%]
基于活性的蛋白质组学分析法研究microRNA靶点：连接酶活性与MicroRNA-185功能之间的关联
Roxana Filip,Geneviève F Desrochers,David M Lefebvre et al.
Roxana Filip et al.
MicroRNAs (miRNAs) act as cellular signal transducers through repression of protein translation. Elucidating targets using bioinformatics and traditional quantitation methods is often insufficient to uncover global miRNA function. Herein, a...
A SUMO1-Derived Peptide Targeting SUMO-Interacting Motif Inhibits α-Synuclein Aggregation [0.03%]
一种针对SUMO-相互作用基序的SUMO1衍生多肽抑制α-突触核蛋白聚集
Zhaohui Liang,Ho Yin Edwin Chan,Marianne M Lee et al.
Zhaohui Liang et al.
The accumulation of α-synuclein amyloid fibrils in the brain is linked to Parkinson's disease and other synucleinopathies. The intermediate species in the early aggregation phase of α-synuclein are involved in the emergence of amyloid tox...
Ruth Nussinov,Hyunbum Jang,Attila Gursoy et al.
Ruth Nussinov et al.
Intuitively, functional states should be targeted; not nonfunctional ones. So why could drugging the inactive K-Ras4BG12Cwork-but drugging the inactive kinase will likely not? The reason is the distinct oncogenic mechanisms. Kinase driver m...
Re-wiring the regulation of the formicamycin biosynthetic gene cluster to enable the development of promising antibacterial compounds [0.03%]
重构蜂蚁素生物合成基因簇调控网络以开发具有前景的抗菌化合物
Rebecca Devine,Hannah P McDonald,Zhiwei Qin et al.
Rebecca Devine et al.
The formicamycins are promising antibiotics first identified in Streptomyces formicae KY5, which produces the compounds at low levels. Here, we show that by understanding the regulation of the for biosynthetic gene cluster (BGC), we can rew...
Investigating the mechanism of action of aggregation-inducing antimicrobial Pept-ins [0.03%]
研究聚集诱导抗菌肽的机制作用
Guiqin Wu,Laleh Khodaparast,Ladan Khodaparast et al.
Guiqin Wu et al.
Aggregation can be selectively induced by aggregation-prone regions (APRs) contained in the target proteins. Aggregation-inducing antimicrobial peptides (Pept-ins) contain sequences homologous to APRs of target proteins and exert their bact...