TG003

TG003 is a potent inhibitor of Clk1/Sty; inhibits Clk1 and Clk4 with IC₅₀ values of 20 and 15 nM, respectively^[1]. IC50 & Target:IC50: 20 nM (Clk1), 200 nM (Clk2), >10 μM (Clk3), 15 nM (Clk4)^[1] In Vitro: TG003, shows the most potent effect on Clk1/Sty and Clk4 (IC₅₀, 15–20 nM) and lesser on Clk2 (200 nM). TG003 inhibits SF2/ASF-dependent splicing of β-globin pre-mRNA in vitro by suppression of Clk-mediated phosphorylation. It suppresses serine/arginine-rich protein phosphorylation, dissociation of nuclear speckles, and Clk1/Sty-dependent alternative splicing in mammalian cells^[1]. The small drug TG003 increases endogenous expression of p53β and p53γ protein isoforms by modulation of TP53 intron 9 alternative splicing^[2]. In Vivo: Intrathecal injection of either TG003 (1-100 pM) or IC261 (0.1-1 nM) dose-dependently decreases mechanical allodynia and thermal hyperalgesia induced by carrageenan or CFA^[3].