1.
ACS Med Chem Lett
; 13(9): 1500-1509, 2022 Sep 08.
Artículo
en Inglés
| MEDLINE
| ID: mdl-36110386
RESUMEN
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.