期刊文献+
共找到4篇文章
< 1 >
每页显示 20 50 100
Chemical screening links disulfiram with cardiac protection after ischemic injury 被引量:1
1
作者 Yuanyuan Chen Jianyong Du +5 位作者 Lixia Zheng Zihao Wang Zongwang Zhang Zhengyuan Wu Xiaojun Zhu Jing-Wei Xiong 《Cell Regeneration》 CAS 2023年第1期163-173,共11页
Ischemia-reperfusion injury occurs after reperfusion treatment for patients suffering myocardial infarction,however the underlying mechanisms are incompletely understood and effective pharmacological interventions are... Ischemia-reperfusion injury occurs after reperfusion treatment for patients suffering myocardial infarction,however the underlying mechanisms are incompletely understood and effective pharmacological interventions are limited.Here,we report the identification and characterization of the FDA-approved drug disulfiram(DSF)as a cardioprotective compound.By applying high-throughput chemical screening,we found that DSF decreased H_(2)O_(2)-induced cardiomyocyte death by inhibiting Gasdermin D,but not ALDH1,in cardiomyocytes.Oral gavage of DSF decreased myocardial infarct size and improved heart function after myocardial ischemia-reperfusion injury in rats.Therefore,this work reveals DSF as a potential therapeutic compound for the treatment of ischemic heart disease. 展开更多
关键词 Small molecule High-throughput chemical screening DISULFIRAM Gasdermin D Ischemia/reperfusion injury Rat cardiomyocytes
原文传递
Identification and Preliminary Characterization of a New Chemical Affecting Glucosyltransferase Activities Involved in Plant Cell Wall Biosynthesis 被引量:1
2
作者 Olga Zabotina Erik Maim +2 位作者 Georgia Drakakaki Vincent Bulone Natasha Raikhel 《Molecular Plant》 SCIE CAS CSCD 北大核心 2008年第6期977-989,共13页
Chemical genetics as a part of chemical genomics is a powerful and fast developing approach to dissect biological processes that may be difficult to characterize using conventional genetics because of gene redundancy ... Chemical genetics as a part of chemical genomics is a powerful and fast developing approach to dissect biological processes that may be difficult to characterize using conventional genetics because of gene redundancy or lethality and, in the case of polysaccharide biosynthesis, plant flexibility. Polysaccharide synthetic enzymes are located in two main compartments--the Golgi apparatus and plasma membrane-and can be studied in vitro using membrane fractions. Here, we first developed a high-throughput assay that allowed the screening of a library of chemicals with a potential effect on glycosyltransferase activities. Out of the 4800 chemicals screened for their effect on Golgi glucosyltransferases, 66 compounds from the primary screen had an effect on carbohydrate biosynthesis. Ten of these compounds were confirmed to inhibit glucose incorporation after a second screen. One compound exhibiting a strong inhibition effect (ID 6240780 named chemical A) was selected and further studied. It reversibly inhibits the transfer of glucose from UDP-glucose by Golgi membranes, but activates the plasma membrane-bound callose synthase. The inhibition effect is dependent on the chemical structure of the compound, which does not affect endomembrane morphology of the plant cells, but causes changes in cell wall composition. Chemical A represents a novel drug with a great potential for the study of the mechanisms of Golgi and plasma membrane-bound glucosyltransferases. 展开更多
关键词 cell walls callose synthase chemical screening and identification GLYCOSYLTRANSFERASE GOLGI plasma membrane
原文传递
Chemical screen identifies shikonin as a broad DNA damage response inhibitor that enhances chemotherapy through inhibiting ATM and ATR 被引量:1
3
作者 Fangfang Wang Sora Jin +6 位作者 Franklin Mayca Pozo Danmei Tian Xiyang Tang Yi Dai Xinsheng Yao Jinshan Tang Youwei Zhang 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2022年第3期1339-1350,共12页
DNA damage response(DDR)is a highly conserved genome surveillance mechanism that preserves cell viability in the presence of chemotherapeutic drugs.Hence,small molecules that inhibit DDR are expected to enhance the an... DNA damage response(DDR)is a highly conserved genome surveillance mechanism that preserves cell viability in the presence of chemotherapeutic drugs.Hence,small molecules that inhibit DDR are expected to enhance the anti-cancer effect of chemotherapy.Through a recent chemical library screen,we identified shikonin as an inhibitor that strongly suppressed DDR activated by various chemotherapeutic drugs in cancer cell lines derived from different origins.Mechanistically,shikonin inhibited the activation of ataxia telangiectasia mutated(ATM),and to a lesser degree ATM and RAD3-related(ATR),two master upstream regulators of the DDR signal,through inducing degradation of ATM and ATR-interacting protein(ATRIP),an obligate associating protein of ATR,respectively.As a result of DDR inhibition,shikonin enhanced the anti-cancer effect of chemotherapeutic drugs in both cell cultures and in mouse models.While degradation of ATRIP is proteasome dependent,that of ATM depends on caspase-and lysosome-,but not proteasome.Overexpression of ATM significantly mitigated DDR inhibition and cell death induced by shikonin and chemotherapeutic drugs.These novel findings reveal shikonin as a pan DDR inhibitor and identify ATM as a primary factor in determining the chemo sensitizing effect of shikonin.Our data may facilitate the development of shikonin and its derivatives as potential chemotherapy sensitizers through inducing ATM degradation. 展开更多
关键词 chemical screen SHIKONIN DNA damage Response ATM ATR ATRIP Protein degradation Chemo sensitizing
原文传递
An Integrated Systems Biology Approach Identifies ZIKV and DENV Replication
4
作者 Guang Song Emily M.Lee +22 位作者 Jianbo Pan Miao Xu Hee-Sool Rho Yichen Cheng Nadia Whitt Shu Yang Jennifer Kouznetsova Carleen Klumpp-Thomas Samuel G.Michael Cedric Moore Ki-Jun Yoon Kimberly M.Christian Anton Simeonov Wenwei Huang Menghang Xia Ruili Huang Madhu Lal-Nag Hengli Tang Wei Zheng Jiang Qian Hongjun Song Guo-li Ming Heng Zhu 《Genomics, Proteomics & Bioinformatics》 SCIE CAS CSCD 2021年第1期108-122,共15页
The Zika virus(ZIKV)and dengue virus(DENV)flaviviruses exhibit similar replicative processes but have distinct clinical outcomes.A systematic understanding of virus–host protein–protein interaction networks can reve... The Zika virus(ZIKV)and dengue virus(DENV)flaviviruses exhibit similar replicative processes but have distinct clinical outcomes.A systematic understanding of virus–host protein–protein interaction networks can reveal cellular pathways critical to viral replication and disease pathogenesis.Here we employed three independent systems biology approaches toward this goal.First,protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and20,240 human proteins revealed multiple conserved cellular pathways and protein complexes,including proteasome complexes.Second,an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this process.Third,high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds,including six proteasome inhibitors that suppress both ZIKV and DENV replication.Integrative analyses of these orthogonal datasets pinpoint proteasomes as critical host machinery for ZIKV/DENV replication.Our study provides multi-omics datasets for further studies of flavivirus–host interactions,disease pathogenesis,and new drug targets. 展开更多
关键词 Protein–protein interaction RNAi screening chemical genetics screening Multi-omics
原文传递
上一页 1 下一页 到第
使用帮助 返回顶部