TG003 (719277-26-6) is a potent, ATP-competitive inhibitor of Clk-family kinases (IC50‘s = 15, 20 and 200 nM for mClk4, 1 and 2 respectively and >10 μM for mClk3).1?Also inhibits DYRK1A/B (IC50‘s = 24 and 34 nM respectively).2 Suppresses serine/arginine-rich protein phosphorylation, dissociation of nuclear speckles and Clk1/Sty-dependent alternative splicing in mammalian cells.1?TG003 affects the regulation of alternative splicing by phosphorylation of SR protein both in vitro and in vivo. Promotes skipping of exon 31 in the endogenous dystrophin gene.3 TG003 increases levels of Clk1/4 mature mRNAs by promoting splicing of the intron-retaining RNAs.4
