TG003

"目录号: HY-15338

Cell Cycle/DNA Damage-

TG003是高效的Clk1/Sty抑制剂，抑制Clk1 和Clk4的IC50值分别为20和15 nM。

CDK

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生物活性

Description

TG003 is a potent inhibitor ofClk1/Sty; inhibits Clk1 and Clk4 withIC50values of 20 and 15 nM, respectively.

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-mRNAin vitroby 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].

References

[1].Muraki M, et al. Manipulation of alternative splicing by a newly developed inhibitor of Clks. J Biol Chem. 2004 Jun 4;279(23):24246-54.

[2].Marcel V, et al. Modulation of p53β and p53γ expression by regulating the alternative splicing of TP53 gene modifies cellular response. Cell Death Differ. 2014 Sep;21(9):1377-87.

[3].Kurihara T, et al. Alleviation of behavioral hypersensitivity in mouse models of inflammatory pain with two structurally different casein kinase 1 (CK1) inhibitors. Mol Pain. 2014 Mar 10;10:17.