TG003

Description

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 β-globin pre-mRNA at 1 μM in vitro. At 10 μM, TG003 rescues the embryonic defects induced by excessive Clk activity in Xenopus.

Uses

TG003 can be used as a potent CDC-2 kinase inhibitor, allowing for research into identification of signaling pathways and possible therapeutic treatments.

Uses

Cdc2-Like Kinase Inhibitor, TG003 is a benzothiazole agent that acts as a specific and ATP-competitive inhibitor of Clk family members. Reports show that TG003 modifies the regulation of alternative splicing modulated by phosphorylation of SR proteins in vitro, and rescues defects in the development of Xenopus caused by an overabundance of Clk activity.

Uses

TG003 has been used in PAC1 cell culture and in vitro kinase assays.

Biochem/physiol Actions

TG003, a CLK (cdc2-like kinase) family inhibitor is used as a drug for duchenne muscular dystrophy.

References

[1] MICHIKO MURAKI. Manipulation of alternative splicing by a newly developed inhibitor of Clks.[J]. The Journal of Biological Chemistry, 2004: 24246-24254. DOI: 10.1074/jbc.m314298200