Structure guided discovery of small molecule ligands targeting the oncomiR-1 NPSL2 hairpin.

ABSTRACT: NPSL2 is a stem loop element within the oncomiR-1 polycistronic primary microRNA (miRNA) cluster. NPSL2 is predicted to mediate conformational rearrangements within oncomiR-1 to regulate the biogenesis of certain miRNA elements within the cluster. The regulatory role of NPSL2 makes it a promising target for small molecule ligands, which we explored through structure-based small molecule ligand discovery. Starting with an NMR-derived ensemble of NPSL2 structures, we identified ligandable cavities within NPSL2 using RNACavityMiner. We then used molecular docking to screen the ZINC library against these cavities to identify potential small molecule hits. A sampling of commercially available compounds from the initial hits were purchased for experimental characterization by saturation transfer

SUBMITTER: Arhin G 

PROVIDER: S-EPMC12354814 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature