|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Discovery of a highly specific ^(18)F-labeled PET ligand for phosphodiesterase 10A enabled by novel spirocyclic iodonium ylide radiofluorination显示文摘As a member of cyclic nucleotide phosphodiesterase(PDE)enzyme family,PDE10A is in charge of the degradation of cyclic adenosine(cAMP)and guanosine monophosphates(cGMP).While PDE10A is primarily expressed in the medium spiny neurons of the striatum,it has been implicated in a variety of neurological disorders.Indeed,inhibition of PDE10A has proven to be of potential use for the treatment of central nervous system(CNS)pathologies caused by dysfunction of the basal ganglia–of which the striatum constitutes the largest component.A PDE10A-targeted positron emission tomography(PET)radioligand would enable a better assessment of the pathophysiologic role of PDE10A,as well as confirm the relationship between target occupancy and administrated dose of a given drug candidate,thus accelerating the development of effective PDE10A inhibitors.In this study,we designed and synthesized a novel ^(18)F-aryl PDE10A PET radioligand,codenamed[^(18)F]P10A-1910([^(18)F]9),in high radiochemical yield and molar activity via spirocyclic iodonium ylide-mediated radiofluorination.[^(18)F]9 possessed good in vitro binding affinity(IC_(50)=2.1 nmol/L)and selectivity towards PDE10A.Further,[^(18)F]9 exhibited reasonable lipophilicity(logD=3.50)and brain permeability(P_(app)>10×10^(−6) cm/s in MDCK-MDR1 cells).PET imaging studies of[^(18)F]9 revealed high striatal uptake and excellent in vivo specificity with reversible tracer kinetics.Preclinical studies in rodents revealed an improved plasma and brain stability of[^(18)F]9 when compared to the current reference standard for PDE10A-targeted PET,[^(18)F]MNI659.Further,dose–response experiments with a series of escalating doses of PDE10A inhibitor 1 in rhesus monkey brains confirmed the utility of[^(18)F]9 for evaluating target occupancy in vivo in higher species.In conclusion,our results indicated that[^(18)F]9 is a promising PDE10A PET radioligand for clinical translation. | Zhiwei Xiao Huiyi Wei Yi Xu Ahmed Haider Junjie Wei Shiyu Yuan Jian Rong Chunyu Zhao Guocong Li Weibin Zhang Huangcan Chen Yuefeng Li Lingling Zhang Jiyun Sun Shaojuan Zhang Hai-Bin Luo Sen Yan Qijun Cai Lu Hou Chao Che Steven H.Liang Lu Wang | 2022 | Acta Pharmaceutica Sinica B2022，12，4： | 0 |
| 2 | Secreted LRPAP1 binds and triggers IFNAR1 degradation to facilitate virus evasion from cellular innate immunity显示文摘variety of ways to antagonize host defense through eliminating IFN-signaling intracellularly for decades.However,the way by viruses target IFN-signaling extracellularly has not been discovered.Infection by both coronavirus SARS-CoV-2 and enterovirus 71(EV71 or EV-A71)can cause severe diseases such as neurological disorders and even death in children. | Huangcan Li Xiong Wang Yiran Wang Yichen Li Ying Chen Yin-Ting Wong Jufang He Ming-Liang He | 2023 | Signal Transduction and Targeted Therapy2023，8，10： | 0 |
| 3 | Stress proteins:the biological functions in virus infection,present and challenges for target-based antiviral drug development显示文摘Stress proteins(SPs)including heat-shock proteins(HSPs),RNA chaperones,and ER associated stress proteins are molecular chaperones essential for cellular homeostasis.The major functions of HSPs include chaperoning misfolded or unfolded polypeptides,protecting cells from toxic stress,and presenting immune and inflammatory cytokines.Regarded as a double-edged sword,HSPs also cooperate with numerous viruses and cancer cells to promote their survival.RNA chaperones are a group of heterogeneous nuclear ribonucleoproteins(hnRNPs),which are essential factors for manipulating both the functions and metabolisms of pre-mRNAs/hnRNAs transcribed by RNA polymerase II.hnRNPs involve in a large number of cellular processes,including chromatin remodelling,transcription regulation,RNP assembly and stabilization,RNA export,virus replication,histonelike nucleoid structuring,and even intracellular immunity.Dysregulation of stress proteins is associated with many human diseases including human cancer,cardiovascular diseases,neurodegenerative diseases(e.g.,Parkinson’s diseases,Alzheimer disease),stroke and infectious diseases.In this review,we summarized the biologic function of stress proteins,and current progress on their mechanisms related to virus reproduction and diseases caused by virus infections.As SPs also attract a great interest as potential antiviral targets(e.g.,COVID-19),we also discuss the present progress and challenges in this area of HSP-based drug development,as well as with compounds already under clinical evaluation. | Qianya Wan Dan Song Huangcan Li Ming-liang He | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 0 |
| 4 | Overview of Rattan Plantation Management显示文摘Rattans are climbing spiny plants that are regarded as an important kind of commercial non-timber forest products. Rattan resources are dwindling rapidly due to over-exploitation in the wild and the loss of tropical forest cover. These threaten the sustainable utilization of rattan resources and long-term survival of the rattan industry. The development of rattan plantation and the improvement of management technique are hence important. The major issues on plantation management are reviewed in this pap... | YANG Jinchang YIN Guangtian XU Huangcan LI Rongsheng YANG HuaResearch Institute of Tropical forestry. Chinese Academy of Forestry. Guangzhou 510520. P.R.China | 2003 | Chinese Forestry Science and Technology2003，2，3： | 0 |
您所在的机构暂未开通此部分的功能，请联系管理员