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Mutations in RNA splicing factor genes including SF3B1, U2AF1 , SRSF2 , and ZRSR2 have been reported to contribute to development of myeloid neoplasms including myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (sAML). Chemical tools targeting cells carrying these mutant genes remain limited and underdeveloped. Among the four proteins, mutant U2AF1 (U2AF1 mut ) acquires an altered 3' splice site selection preference and co-operates with the wild-type U2AF1 (U2AF1 wt ) to change various gene isoform patterns to support MDS cells survival and proliferation. U2AF1 mutations in MDS cells are always heterozygous and the cell viability is reduced when exposed to additional insult affecting U2AF1 wt function. To investigate if the pharmacological inhibition of U2AF1 wt function can provoke drug-induced vulnerability of cells harboring U2AF1 mut , we conducted a fragment-based library screening campaign to discover compounds targeting the U2AF homology domain (UHM) in U2AF1 that is required for the formation of the U2AF1/U2AF2 complex to define the 3' splice site. The most promising hit ( SF1-8 ) selectively inhibited growth of leukemia cell lines overexpressing U2AF1 mut and human primary MDS cells carrying U2AF1 mut . RNA-seq analysis of K562-U2AF1 mut following treatment with SF1-8 further revealed alteration of isoform patterns for a set of proteins that impair or rescue pathways associated with endocytosis, intracellular vesicle transport, and secretion. Our data suggested that further optimization of SF1-8 is warranted to obtain chemical probes that can be used to evaluate the therapeutic concept of inducing lethality to U2AF1 mut cells by inhibiting the U2AF1 wt protein., Competing Interests: The authors declare no competing financial interests. Readers welcome to comment on the online version of the paper. Additional Declarations: There is NO Competing Interest.

An efficient selenylative cyclization of aryl-alkynones with diselenides in the presence of iron(III)chloride at room temperature to prepare 3-seleno-2-naphthols in good yields has been described. Furthermore, the resulting products were transformed into selenyl-naphthofuran and selenyl-1,2-naphthoquinone derivatives.