Albert A Antolin,Paul A Clarke,Ian Collins et al.
Albert A Antolin et al.
Most small molecules interact with several target proteins but this polypharmacology is seldom comprehensively investigated or explicitly exploited during drug discovery. Here, we use computational and experimental methods to identify and s...
Rodrigo A Gama-Brambila,Jie Chen,Jun Zhou et al.
Rodrigo A Gama-Brambila et al.
The proteolysis-targeting chimeras (PROTACs) are a new technology to degrade target proteins. However, their clinical application is limited currently by lack of chemical binders to target proteins. For instance, it is still unknown whether...
Toxoplasma gondii serine hydrolases regulate parasite lipid mobilization during growth and replication within the host [0.03%]
托氏子孢子虫丝氨酸水解酶在宿主体内生长和自我复制过程中调节寄生脂质动员
Ouma Onguka,Brett M Babin,Markus Lakemeyer et al.
Ouma Onguka et al.
The intracellular protozoan parasite Toxoplasma gondii must scavenge cholesterol and other lipids from the host to facilitate intracellular growth and replication. Enzymes responsible for neutral lipid synthesis have been identified but the...
Probing the binding of interleukin-23 to individual receptor components and the IL-23 heteromeric receptor complex in living cells using NanoBRET [0.03%]
应用NanoBRET技术研究活细胞中IL-23与其受体单个组分和异源二聚体复合物的结合动力学
Charles S Lay,Angela Bridges,Joelle Goulding et al.
Charles S Lay et al.
Interleukin-23 (IL-23) is a pro-inflammatory cytokine involved in the host defense against pathogens but is also implicated in the development of several autoimmune disorders. The IL-23 receptor has become a key target for drug discovery, b...
Exploiting ubiquitin ligase cereblon as a target for small-molecule compounds in medicine and chemical biology [0.03%]
利用泛素连接酶cereblon作为医药和化学生物学中的小分子化合物靶点
Takumi Ito,Yuki Yamaguchi,Hiroshi Handa
Takumi Ito
Cereblon (CRBN), originally identified as a gene associated with intellectual disability, was identified as primary target of thalidomide. Accumulating evidence has shown that CRBN is a substrate receptor of Cullin Ring E3 ubiquitin ligase ...
Rebecca L Myers,Peter S Klein
Rebecca L Myers
In this issue of Cell Chemical Biology, Cheng et al. (2021) identify a class of drugs that activate a mitotic stress-dependent signaling cascade, which culminates in p53 activation and Wnt pathway inhibition (PAWI). PAWI compounds may there...
Christine S C Ng,Steven M Banik
Christine S C Ng
Transcription factors play central roles in numerous diseases yet are notoriously challenging targets for drug development. In this issue of Cell Chemical Biology, Samarasinghe et al. (2021) describe a modular approach to targeting transcri...
Akiko Hata,Giorgio Lagna
Akiko Hata
SMAD4 mutations that disrupt its interaction with SMAD3 and attenuate tumor suppression by TGF-β are major oncogenic drivers. Tang et al. (2020) report the discovery of small molecules that restore the SMAD4:SMAD3 complex and its cytostati...
Targeting allostery in the Dynein motor domain with small molecule inhibitors [0.03%]
靶向动力蛋白motor域的allostery并用小分子抑制剂阻止其活性
Cristina C Santarossa,Keith J Mickolajczyk,Jonathan B Steinman et al.
Cristina C Santarossa et al.
Cytoplasmic dyneins are AAA (ATPase associated with diverse cellular activities) motor proteins responsible for microtubule minus-end-directed intracellular transport. Dynein's unusually large size, four distinct nucleotide-binding sites, a...
Naturally occurring three-way junctions can be repurposed as genetically encoded RNA-based sensors [0.03%]
天然三向接头可以被重新设计为基于RNA的遗传传感器
Jared D Moon,Jiahui Wu,Sourav K Dey et al.
Jared D Moon et al.
Small molecules can be imaged in living cells using biosensors composed of RNA. However, RNA-based devices are difficult to design. Here, we describe a versatile platform for designing RNA-based fluorescent small-molecule sensors using natu...