ArticleACS chemical biology2025
Chemical Probe Discovery for DEAD-Box RNA-Binding Protein DDX21 Using Small-Molecule Microarrays.
Article in ACS chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
- Identification and optimization of first-in-class RNA helicase inhibitors of DDX1, LGP2, and MDA5.European journal of medicinal chemistry · 2026Article
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3 authors.
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Abstract
The DEAD-box family of ATPases plays a critical role in nearly all stages of RNA metabolism, from transcription to degradation, and serves as a major regulator of biomolecular condensates. Dysregulation of DEAD-box proteins is well-established in a variety of diseases, including cancer and neurodegenerative disorders, making them attractive therapeutic targets. However, their classification as "undruggable" has historically hindered small-molecule-based modulation. In this study, we focus on DDX21, a member of the DEAD-box family involved in ribosome biogenesis and transcription regulation. As a proof of concept for targeting such RNA-binding proteins, we developed a lysate-based small-molecule microarray platform to identify compounds that directly bind DDX21. This screen led to the discovery of KI-DX-014, a small-molecule compound capable of inhibiting the interaction of DDX21 with RNA. KI-DX-014 modulated the RNA-dependent functions of DDX21, including its ATPase activity and biomolecular condensate formation. Furthermore, KI-DX-014 attenuated the DDX21-dependent release of P-TEFb from the 7SK snRNP complex
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