In vivo bioluminescence imaging of granzyme B activity in tumor response to cancer immunotherapy [0.03%]
肿瘤免疫治疗的瘤内粒酶B活化的体内生物发光成像研究
Min Chen,Kaixiang Zhou,Sheng-Yao Dai et al.
Min Chen et al.
Cancer immunotherapy has revolutionized the treatment of cancer, but only a small subset of patients benefits from this new treatment regime. Imaging tools are useful for early detection of tumor response to immunotherapy and probing the dy...
Target protein localization and its impact on PROTAC-mediated degradation [0.03%]
靶蛋白定位及其对PROTAC介导降解的影响
Luke M Simpson,Lorraine Glennie,Abigail Brewer et al.
Luke M Simpson et al.
Proteolysis-targeting chimeras (PROTACs) bring a protein of interest (POI) into spatial proximity of an E3 ubiquitin ligase, promoting POI ubiquitylation and proteasomal degradation. PROTACs rely on endogenous cellular machinery to mediate ...
Guangyan Du,Jie Jiang,Nathaniel J Henning et al.
Guangyan Du et al.
Targeted protein degradation (TPD) uses small molecules to recruit E3 ubiquitin ligases into the proximity of proteins of interest, inducing ubiquitination-dependent degradation. A major bottleneck in the TPD field is the lack of accessible...
In vivo drug discovery for increasing incretin-expressing cells identifies DYRK inhibitors that reinforce the enteroendocrine system [0.03%]
体内药物发现增加肠内分泌细胞中表达肠促胰素的化合物识别出增强肠内分泌系统的Dyrk抑制剂
Lianhe Chu,Michishige Terasaki,Charlotte L Mattsson et al.
Lianhe Chu et al.
Analogs of the incretin hormones Gip and Glp-1 are used to treat type 2 diabetes and obesity. Findings in experimental models suggest that manipulating several hormones simultaneously may be more effective. To identify small molecules that ...
Repurposing the repurposed: thalidomide analogs as immune stimulants to overcome T cell exhaustion [0.03%]
再利用的药物再生用：thalidomide衍生物作为免疫刺激剂以克服T细胞衰竭
Mikołaj Słabicki,Adam S Sperling
Mikołaj Słabicki
In this issue of Cell Chemical Biology, Geng and colleagues employ a novel mouse model of humanized cereblon (Crbn) to provide insights into the immunomodulatory effects of lenalidomide and provide rationale for potential therapeutic combin...
Discovery of compounds that reactivate p53 mutants in vitro and in vivo [0.03%]
用于活体和离体实验重新激活p53突变体的化合物的发现
Geetha Durairaj,Özlem Demir,Bryant Lim et al.
Geetha Durairaj et al.
The tumor suppressor p53 is the most frequently mutated protein in human cancer. The majority of these mutations are missense mutations in the DNA binding domain of p53. Restoring p53 tumor suppressor function could have a major impact on t...
Aberrant human ClpP activation disturbs mitochondrial proteome homeostasis to suppress pancreatic ductal adenocarcinoma [0.03%]
异常的人类ClpP激活会干扰线粒体蛋白质组稳态以抑制胰腺导管腺癌
Pengyu Wang,Tao Zhang,Xinjing Wang et al.
Pengyu Wang et al.
The mitochondrial caseinolytic protease P (ClpP) is a target candidate for treating leukemia; however, the effects of ClpP modulation on solid tumors have not been adequately explored. Here, we report a potent activator of ClpP with the the...
Pharmacological perturbation of thiamine metabolism sensitizes Pseudomonas aeruginosa to multiple antibacterial agents [0.03%]
药理学手段干扰硫胺素代谢使绿脓杆菌对多种抗菌剂敏感化
Hyung Jun Kim,Yingying Li,Michael Zimmermann et al.
Hyung Jun Kim et al.
New therapeutic concepts are critically needed for carbapenem-resistant Pseudomonas aeruginosa, an opportunistic pathogen particularly recalcitrant to antibiotics. The screening of around 230,000 small molecules yielded a very low hit rate ...
Native chemical ligation approach to sensitively probe tissue acyl-CoA pools [0.03%]
用于灵敏检测组织酰基-CoA的方法
Andrew M James,Abigail A I Norman,Jack W Houghton et al.
Andrew M James et al.
During metabolism, carboxylic acids are often activated by conjugation to the thiol of coenzyme A (CoA). The resulting acyl-CoAs comprise a group of ∼100 thioester-containing metabolites that could modify protein behavior through non-enzym...
Sarah van Tol,Adam Hage,Ricardo Rajsbaum
Sarah van Tol
Developing broad-spectrum, host-directed antiviral therapeutics can be adapted to combat emerging viruses. In this issue of Cell Chemical Biology, Maarifi and colleagues implement a Nano luciferase reporter-based protein complementation ass...