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Cdc2-like kinase (Clk), among a number of other kinases, phosphorylates serine/arginine-rich proteins which play a role in alternative splicing of pre-mRNA. The Clk family consists of four members, which include Clk1/Sty and Clk2-4. TG003 is a novel benzothiazole compound that demonstrates potent inhibition of Clk1/Sty and Clk4 with IC50 values of 20 and 15 nM, respectively. TG003 exhibits considerably weaker inhibition of Clk2 and Clk3 (IC50 = 200 nM and >10 µM, respectively). Through suppression of Clk-mediated phosphorylation, TG003 inhibits SF2/ASF-dependent splicing of beta-globin pre-mRNA at 1 µM in vitro. At 10 µM, TG003 rescues the embryonic defects induced by excessive Clk activity in Xenopus.