The cdc2-like kinases (CLKs; EC 2.7.12.1) are CMGC group (cyclin-dependent kinases (CDKs), mitogen-activated protein kinases (MAP kinases), glycogen synthase kinases (GSK) and CDK-like kinases) dual-specificity kinases, capable of autophosphorylation at tyrosine residues while phosphorylating substrates at serine and threonine residues. They make up an essential and typically large group of kinases found in all eukaryotes. Four isoforms, CLK1–CLK4 are known to date, which impact mRNA splicing by phosphorylating the serine- and arginine-rich (SR) family of splicing proteins. The first selective small-molecule inhibitor of the CLK kinases, benzothiazole TG 003 (Axon 1765) is a potent inhibitor of CLK1 (20 nM) and CLK4 (15 nM), exhibits modest activity against CLK2 (200 nM), and is inactive against CLK3[1].