The Cdc2-like kinases (Clk’s) and the dual-specificity tyrosine phosphorylation-regulated kinases (Dyrk’s) have specified roles in gene splicing. Specifically, the Clk class of enzymes has been shown to phosphorylate the serine- and arginine-rich (SR) proteins, which are a major component of the spliceosome. Dyrk1A has been shown to accumulate in nuclear speckles, where it interacts and activates splicing factors. It has been hypothesized that inhibition of these targets may offer a mechanism to control splicing. This probe represents our continued examination of substituted 6-arylquinazolin-4-amines as Clk/Dyrk inhibitors. Several of the most potent inhibitors, including ML167 (CID 44968231) were validated as being highly selective within a comprehensive kinome scan. Appropriate aqueous solubility and stability were found for this agent.