Identification of covalent inhibitors that disrupt M. tuberculosis growth by targeting multiple serine hydrolases involved in lipid metabolism [0.03%]
识别共价抑制剂通过作用于多个参与脂质代谢的丝氨酸水解酶来破坏结核分枝杆菌生长
Brett M Babin,Laura J Keller,Yishay Pinto et al.
Brett M Babin et al.
The increasing incidence of antibiotic-resistant Mycobacterium tuberculosis infections is a global health threat necessitating the development of new antibiotics. Serine hydrolases (SHs) are a promising class of targets because of their imp...
Identification of cell wall synthesis inhibitors active against Mycobacterium tuberculosis by competitive activity-based protein profiling [0.03%]
通过竞争性活性基于蛋白谱分析识别抑制结核分枝杆菌细胞壁合成的抑制剂
Michael Li,Hiren V Patel,Armand B Cognetta rd et al.
Michael Li et al.
The identification and validation of a small molecule's targets is a major bottleneck in the discovery process for tuberculosis antibiotics. Activity-based protein profiling (ABPP) is an efficient tool for determining a small molecule's tar...
Stella M K Glasauer,Therese Triemer,Anne B Neef et al.
Stella M K Glasauer et al.
Asymmetric inheritance of sister chromatids has long been predicted to be linked to discordant fates of daughter cells and even hypothesized to minimize accumulation of mutations in stem cells. Here, we use (2'S)-2'-deoxy-2'-fluoro-5-ethyny...
Identification of a PCSK9-LDLR disruptor peptide with in vivo function [0.03%]
具有体内功能的PCSK9-LDLR抑制肽的识别
Margaret E Brousseau,Kevin B Clairmont,Glen Spraggon et al.
Margaret E Brousseau et al.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates plasma low-density lipoprotein cholesterol (LDL-C) levels by promoting hepatic LDL receptor (LDLR) degradation. Therapeutic antibodies that disrupt PCSK9-LDLR binding reduce LD...
Hypoxia-activated KDAC inhibitor: Taking a breath from untargeted therapy [0.03%]
缺氧激活的KDAC抑制剂：从无针对性治疗中解脱出来
Maximilian Staudt,Manfred Jung
Maximilian Staudt
Use of hypoxia-activated prodrugs has emerged as a strategy for selectively targeting tumors in hypoxic conditions harboring reductive environments. In this issue of Cell Chemical Biology, Skwarska et al. (2021) report a hypoxia-activated p...
Break Away: FKBP12 sequestration as a target for increasing BMP activity [0.03%]
脱离：将FKBP12隔离以增加BMP活性为目标
Martha C Taubert,Felix Hausch
Martha C Taubert
Bone morphogenetic protein (BMP) signaling contributes to acute kidney injury (AKI), a common disease without adequate treatment options. In this issue of Cell Chemical Biology, Larraufie, Gao and colleagues (Larraufie et al., 2021) show th...
Control of topoisomerase II activity and chemotherapeutic inhibition by TCA cycle metabolites [0.03%]
三羧酸循环代谢物对拓扑异构酶II活性及其化学抑制的控制
Joyce H Lee,Eric P Mosher,Young-Sam Lee et al.
Joyce H Lee et al.
Topoisomerase II (topo II) is essential for disentangling newly replicated chromosomes. DNA unlinking involves the physical passage of one duplex through another and depends on the transient formation of double-stranded DNA breaks, a step e...
Synergistic PIM kinase and proteasome inhibition as a therapeutic strategy for MYC-overexpressing triple-negative breast cancer [0.03%]
PIM激酶和蛋白酶体抑制的联合应用作为治疗MYC过表达的三阴性乳腺癌的策略
Ratika Kunder,Michelle Velyunskiy,Sara F Dunne et al.
Ratika Kunder et al.
Triple-negative breast cancer (TNBC) is the breast cancer subtype with the poorest clinical outcome. The PIM family of kinases has emerged as a factor that is both overexpressed in TNBC and associated with poor outcomes. Preclinical data su...
Development of an intracellular quantitative assay to measure compound binding kinetics [0.03%]
开发用于测量化合物结合动力学的细胞内定量检测方法
Charles S Lay,Daniel A Thomas,John P Evans et al.
Charles S Lay et al.
Contemporary drug discovery typically quantifies the effect of a molecule on a biological target using the equilibrium-derived measurements of IC50, EC50, or KD. Kinetic descriptors of drug binding are frequently linked with the effectivene...
Targeted epigenetic induction of mitochondrial biogenesis enhances antitumor immunity in mouse model [0.03%]
靶向表观遗传诱导线粒体生物发生可增强小鼠模型的抗肿瘤免疫反应
Madhu Malinee,Ganesh Namasivayam Pandian,Hiroshi Sugiyama
Madhu Malinee
Considering the potential of combinatorial therapies in overcoming existing limitations of cancer immunotherapy, there is an increasing need to identify small-molecule modulators of immune cells capable of augmenting the effect of programme...