The beginning of a new era:pioneering direct screens for RNA modulators  

作　　者：F.X.Reymond Sutandy Rebecca George Tharyan Christian Münch 

机构地区：[1]Institute of Biochemistry II,Goethe University Frankfurt,Faculty of Medicine,Frankfurt am Main,Germany [2]Frankfurt Cancer Institute,Frankfurt am Main,Germany [3]CardioPulmonary Institute,Frankfurt am Main,Germany

出　　处：《Signal Transduction and Targeted Therapy》2022年第8期2660-2661,共2页信号转导与靶向治疗（英文）

基　　金：supported by grants from the European Research Council(ERC StG 803565);the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)Project-ID 390339347(Emmy Noether Programme);the EnABLE consortium funded by the Hessian Ministry for Arts and Sciences.

摘　　要：In a recent study published in Nature,1 Aguilar et al.describe the small molecule X1 that targets the long non-coding RNA Xist.Upon X1 binding,Xist changes its structure,which prevents its role in X-chromosome inactivation(XCI).The vast majority of small molecule screens in drug discovery focus on targeting proteins.2,3 However,protein coding sequences merely constitute~1.5%of the human genome and only a small fraction of these proteins are currently targetable.2 In contrast,90%of the human genome is transcribed into RNA in different forms,which makes RNAs compelling targets for small molecule drugs.3 Modulating mRNAs with small molecules could be an alternative route to change the levels of the corresponding protein products and their activities,especially for currently undruggable proteins.Considering the diverse functions carried out by different classes of RNAs in cells,altering RNAs would provide a broad range of potential drug targets in the human genome.While modulating RNAs with small molecules carries a number of advantages,identifying RNA-targeting small molecules has proven difficult;previous compounds had been identified indirectly by phenotypic screens.1–3 Systematic approaches to screen for RNAtargeting compounds had been lacking.

关 键 词：DRUGS SCREEN currently 

分 类 号：R96[医药卫生—药理学]