TG003

Description: TG003 is a novel, potent, selective and ATP-competitive Cdc2-like kinase (Clk) inhibitor with IC50 of 20 nM, 200 nM, and 15 nM for Clk1, Clk2, and Clk4, respectively. It shows no inhibitory effect on Clk3, SRPK1, SRPK2, or PKC. TG003 competed with ATP with Ki value of 0.01 uM on Clk1/Sty. In HeLa cytosolic S100 extract, TG003 inhibited Clk1/Sty-mediated phosphorylation of SF2/ASF, which played an important role in alternative splicing. TG003 inhibited SF2/ASF-dependent splicing of beta-globin pre-mRNA in vitro by suppression of Clk-mediated phosphorylation. TG003 also suppressed serine/arginine-rich protein phosphorylation, dissociation of nuclear speckles, and Clk1/Sty-dependent alternative splicing in mammalian cells. Consistently, administration of TG003 rescued the embryonic defects induced by excessive Clk activity in Xenopus.

References: J Biol Chem. 2004 Jun 4; 279(23):24246-54; PLoS One. 2013; 8(1):e53268.