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10.1124/pr.120.019554

http://scihub22266oqcxt.onion/10.1124/pr.120.019554
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32929000!7495341!32929000
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suck abstract from ncbi


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pmid32929000      Pharmacol+Rev 2020 ; 72 (4): 862-898
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  • RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges #MMPMID32929000
  • Yu AM; Choi YH; Tu MJ
  • Pharmacol Rev 2020[Oct]; 72 (4): 862-898 PMID32929000show ga
  • RNA-based therapies, including RNA molecules as drugs and RNA-targeted small molecules, offer unique opportunities to expand the range of therapeutic targets. Various forms of RNAs may be used to selectively act on proteins, transcripts, and genes that cannot be targeted by conventional small molecules or proteins. Although development of RNA drugs faces unparalleled challenges, many strategies have been developed to improve RNA metabolic stability and intracellular delivery. A number of RNA drugs have been approved for medical use, including aptamers (e.g., pegaptanib) that mechanistically act on protein target and small interfering RNAs (e.g., patisiran and givosiran) and antisense oligonucleotides (e.g., inotersen and golodirsen) that directly interfere with RNA targets. Furthermore, guide RNAs are essential components of novel gene editing modalities, and mRNA therapeutics are under development for protein replacement therapy or vaccination, including those against unprecedented severe acute respiratory syndrome coronavirus pandemic. Moreover, functional RNAs or RNA motifs are highly structured to form binding pockets or clefts that are accessible by small molecules. Many natural, semisynthetic, or synthetic antibiotics (e.g., aminoglycosides, tetracyclines, macrolides, oxazolidinones, and phenicols) can directly bind to ribosomal RNAs to achieve the inhibition of bacterial infections. Therefore, there is growing interest in developing RNA-targeted small-molecule drugs amenable to oral administration, and some (e.g., risdiplam and branaplam) have entered clinical trials. Here, we review the pharmacology of novel RNA drugs and RNA-targeted small-molecule medications, with a focus on recent progresses and strategies. Challenges in the development of novel druggable RNA entities and identification of viable RNA targets and selective small-molecule binders are discussed. SIGNIFICANCE STATEMENT: With the understanding of RNA functions and critical roles in diseases, as well as the development of RNA-related technologies, there is growing interest in developing novel RNA-based therapeutics. This comprehensive review presents pharmacology of both RNA drugs and RNA-targeted small-molecule medications, focusing on novel mechanisms of action, the most recent progress, and existing challenges.
  • |Aptamers, Nucleotide/pharmacology/therapeutic use[MESH]
  • |Betacoronavirus[MESH]
  • |COVID-19[MESH]
  • |Chemistry Techniques, Analytical/methods/standards[MESH]
  • |Clustered Regularly Interspaced Short Palindromic Repeats[MESH]
  • |Coronavirus Infections/drug therapy[MESH]
  • |Drug Delivery Systems/methods[MESH]
  • |Drug Development/organization & administration[MESH]
  • |Drug Discovery[MESH]
  • |Humans[MESH]
  • |MicroRNAs/pharmacology/therapeutic use[MESH]
  • |Oligonucleotides, Antisense/pharmacology/therapeutic use[MESH]
  • |Pandemics[MESH]
  • |Pneumonia, Viral/drug therapy[MESH]
  • |RNA, Antisense/pharmacology/therapeutic use[MESH]
  • |RNA, Messenger/drug effects/pharmacology[MESH]
  • |RNA, Ribosomal/drug effects/pharmacology[MESH]
  • |RNA, Small Interfering/pharmacology/therapeutic use[MESH]
  • |RNA, Viral/drug effects[MESH]
  • |RNA/adverse effects/*drug effects/*pharmacology[MESH]
  • |Ribonucleases/metabolism[MESH]
  • |Riboswitch/drug effects[MESH]


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