ArticleACS medicinal chemistry letters2026
Discrete On-DNA Screening: A Frontier for Rapid Hit-to-Lead Optimization Applied to p38α.
Article in ACS medicinal chemistry letters, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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14 authors.
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Abstract
High-throughput screening (HTS) and DNA-encoded library (DEL) selection are cornerstones of drug discovery but suffer from high operational infrastructure requirements or constraints to affinity-only selections. Herein we report a robust on-DNA compound screening method that bridges this gap, enabling direct functional evaluation of DNA-linked small molecules while bypassing plate-based or selection-wash limitations. To validate this platform, a focused collection of trisubstituted benzamides was synthesized and screened directly on-DNA against p38α MAPK. This methodology rapidly prioritized advanced structures, culminating in the seamless identification of compound
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