Abstract: Embodiments of the disclosure concern identification of suitable inhibitors of components of RNA metabolism, including those involved with splicing, such as RNA helicases. The disclosure includes in vitro screens for small molecule inhibitors that are selective for a group of RNA helicases but that are counter-selective for another group of RNA helicases. In specific embodiments, the disclosure includes a system for inhibitor analysis that includes assay development and optimization that leads to feasible screening of the intended target(s) and continued counter-selection against undesirable targets throughout the process.

Abstract: Embodiments of the disclosure include chemical, genetic, and/or computational systems, methods, and compositions for characterizing RNA helicases for targeting for inhibition, and methods of screening for inhibitors. In specific embodiments, inhibitors of RNA helicases, including RNA helicases for splicing, are identified that have selective targeting of one or more desired RNA helicases but that are also counter-selected such that the inhibitor does not target one or more RNA helicases that would result in toxicity.

Abstract: Disclosed are bifunctional compounds (degraders) that target Wee1 tyrosine kinase for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat disease.