Small molecule targeting of transcription-replication conflict for selective chemotherapy [0.03%]
小分子靶向转录-复制冲突的化疗药物筛选
Long Gu,Min Li,Caroline M Li et al.
Long Gu et al.
Targeting transcription replication conflicts, a major source of endogenous DNA double-stranded breaks and genomic instability could have important anticancer therapeutic implications. Proliferating cell nuclear antigen (PCNA) is critical t...
Catalytic inhibitor of Protein Phosphatase 5 activates the extrinsic apoptotic pathway by disrupting complex II in kidney cancer [0.03%]
蛋白磷酸酶5催化抑制剂通过破坏II型复合物激活肾癌的外源性凋亡途径
Elham F Ahanin,Rebecca A Sager,Sarah J Backe et al.
Elham F Ahanin et al.
Serine/threonine protein phosphatase-5 (PP5) is involved in tumor progression and survival, making it an attractive therapeutic target. Specific inhibition of protein phosphatases has remained challenging because of their conserved catalyti...
Paralog-dependent isogenic cell assay cascade generates highly selective SLC16A3 inhibitors [0.03%]
基于旁系同源物的同基因细胞测定级联生成高选择性的SLC16A3抑制剂
Vojtech Dvorak,Andrea Casiraghi,Claire Colas et al.
Vojtech Dvorak et al.
Despite being considered druggable and attractive therapeutic targets, most of the solute carrier (SLC) membrane transporters remain pharmacologically underexploited. One of the reasons for this is a lack of reliable chemical screening assa...
CLK2 and CLK4 are regulators of DNA damage-induced NF-κB targeted by novel small molecule inhibitors [0.03%]
CLK2和CLK4是DNA损伤诱导的NF-κB信号通路调节因子并可被新型小分子抑制剂靶向作用
Patrick Mucka,Peter Lindemann,Bartolomeo Bosco et al.
Patrick Mucka et al.
Transcription factor NF-κB potently activates anti-apoptotic genes, and its inactivation significantly reduces tumor cell survival following genotoxic stresses. We identified two structurally distinct lead compounds that selectively inhibi...
High-resolution photocatalytic mapping of SARS-CoV-2 spike interactions on the cell surface [0.03%]
SARS-CoV-2刺突蛋白与细胞表面受体高分辨率光催化相互作用图谱
Suprama Datta,Da-Yuan Chen,Alexander H Tavares et al.
Suprama Datta et al.
Identifying virus-host interactions on the cell surface can improve our understanding of viral entry and pathogenesis. SARS-CoV-2, the causative agent of the COVID-19 disease, uses ACE2 as a receptor to enter cells. Yet the full repertoire ...
Mingxing Teng,Nathanael S Gray
Mingxing Teng
The cancer genomics revolution has served up a plethora of promising and challenging targets for the drug discovery community. The field of targeted protein degradation (TPD) uses small molecules to reprogram the protein homeostasis system ...
DELs enable the development of BRET probes for target engagement studies in cells [0.03%]
DEL技术助力开发细胞内作用靶点研究的BRET探针技術
Kelly A Teske,Wenji Su,Cesear R Corona et al.
Kelly A Teske et al.
DNA-encoded libraries (DELs) provide unmatched chemical diversity and starting points for novel drug modalities. Here, we describe a workflow that exploits the bifunctional attributes of DEL ligands as a platform to generate BRET probes for...
S-Nitrosylation-mediated dysfunction of TCA cycle enzymes in synucleinopathy studied in postmortem human brains and hiPSC-derived neurons [0.03%]
SNITRIC氧化修饰诱导的多巴胺能神经元三羧酸循环酶功能障碍与帕金森病病理的关系研究
Paschalis-Thomas Doulias,Hongmei Yang,Alexander Y Andreyev et al.
Paschalis-Thomas Doulias et al.
A causal relationship between mitochondrial metabolic dysfunction and neurodegeneration has been implicated in synucleinopathies, including Parkinson disease (PD) and Lewy body dementia (LBD), but underlying mechanisms are not fully underst...
Agnieszka Grelska,Deepti Sharan,Samuel H Light
Agnieszka Grelska
Elevated bloodstream levels of uric acid, a mammalian purine degradation product, are associated with several noncommunicable diseases. Recent studies by Kasahara et al. and Liu et al. define purine-degrading activities of the gut microbiot...
Xiaolan Deng,Ying Qing,Jianjun Chen
Xiaolan Deng
Immunosuppression contributes to tumor-radiotherapy failure, but the mechanism remains elusive. Wang et al.1 reported that ionizing radiation (IR) induces YTHDF2 expression in myeloid-derived suppressor cells (MDSCs) via an IR-YTHDF2-NF-κB...