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ID: ALA5143763

Journal: ACS Med Chem Lett

Title: Fragment Ligands of the m6A-RNA Reader YTHDF2.

Authors: Nai F, Nachawati R, Zálešák F, Wang X, Li Y, Caflisch A.

Abstract: We report 17 small-molecule ligands that compete with N6-methyladenosine (m6A) for binding to the m6A-reader domain of YTHDF2 (YT521-B homology domain family 2). We determined their binding mode at high resolution by X-ray crystallography and quantified their affinity by a fluorescence-based binding assay. 6-Cyclopropyluracil and a pyrazolopyrimidine derivative have favorable ligand efficiencies of 0.47 and 0.38 kcal mol-1 per non-hydrogen atom, respectively. They represent useful starting points for hit optimization.

CiteXplore: 36110386

DOI: 10.1021/acsmedchemlett.2c00303