Screening Methods to Identify RNA-Targeting Small Molecules

September 13, 2023
8:00 a.m. PDT / 11:00 a.m. EDT / 16:00 BST / 17:00 CEST - Duration: 60 Minutes


RNA molecules are promising drug targets due to their genomic prevalence, disease involvement, and druggable complex structures. Successful examples include RNA-targeting small molecule drugs for spinal muscular atrophy (SMA), with on-going efforts in other RNA-related diseases.  

Here, we present our toolbox for discovering RNA-targeting small molecules, with a focus on unique DNA-encoded libraries (DEL). Using DEL, we have identified several compounds against diverse RNA targets, including the human SMN2 (survival of motor neuron 2) mRNA. Rigorous validation using established assays such as SPR, ASMS, FID, and cellular splicing assays confirms the functionality of the DEL-selected compound in regulating SMN2 splicing. Additionally, SHAPE-MaP analysis provides insights into the compound’s potential mechanism of action.  

Our findings demonstrate the feasibility of screening RNA-targeting small molecules using DEL. Furthermore, we highlight alternative screening methods to identify RNA-targeting compounds, along with valuable downstream biophysical and biochemical validation techniques. 

Key Learning Objectives:
  • Learn how SHAPE-MaP analysis is efficient for fast RNA structure and binding site verification
  • Understand how specialized DEL, FBDD and ASMS are powerful tools to identify RNA-targeting small molecules
  • Review how various orthogonal assays can be employed to validate RNA-targeting small molecules 
Who Should Attend:
  • Industry leaders, directors, and project managers focused on drug discovery
  • Academic researchers involved in drug discovery projects
  • Biotech/Pharma scientists focused on RNA-based therapeutics
  • Scientists who are interested in new modality-based therapies

Brought to you by:
WuXi AppTec Logo


Dr. Zhifeng Yu
Director of Assay & Screen,
WuXi AppTec
Dr. Ma Zhongyao
Associate Director, Early Discovery,
WuXi AppTec
Kelly McSweeney
Contributing Editor,
C&EN Media Group


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