General description

A cell-permeable piperazinyl-pyrimidine compound that acts as an inhibitor against S6K1 (K_i = 20 nM; IC₅₀ = 160 nM) and MSK1 (IC₅₀ = 950 nM) kinase activity, exhibiting little or much reduced potency against a panel of 75 other protein kinases (IC₅₀ = 4.7, 9.2, 65 µM, respectively, against RSK1, RSK2, and S6K2; ≤27% inhibition of the rest at 1 µM) and 10 lipid kinases (≤6% inhibition at 10 µM). Inhibits IGF1-induced phosphorylation of cellular S6K1 substrates S6 (Ser^235/236 and Ser^240/244), mTOR (Ser²⁴⁴⁸), and Rictor (Thr¹¹³⁵) in serum-starved HEK-293 cultures, but not the phoshorylation of MSK or RSK cellular substrates (CREB Ser¹³³ and GSK3α/β Ser²¹/ Ser⁹, respectively) upon PMA stimulation even at concentrations as high as 10 µM. Inhibition of S6K1 activation by rapamycin (Cat. Nos. 553210, 553211, & 553212) or S6K1 activity by PF-4708671 (75/mg/kg/daily i.p.) are both shown to alleviate heart remodeling and functional damage following left coronary artery ligation-induced MI (myocardial infarction) in mice in vivo. Cellular PF-4708671 treatment is also reported to result in increased S6K1 phosphorylation, likely due to a blockage of down-stream negative feedback mechanism.

A cell-permeable piperazinyl-pyrimidine compound that acts as an inhibitor against S6K1 (K_i = 20 nM; IC₅₀ = 160 nM) and MSK1 (IC₅₀ = 950 nM) kinase activity, exhibiting little or much reduced potency against 85 other protein and lipid kinases (IC₅₀ = 4.7, 9.2, 65 µM, respectively, against RSK1, RSK2, and S6K2; ≤27% inhibition of the rest at 1 µM). Shown to selectively inhibit IGF1- and PMA-stimulated S6K1 substrates phosphorylation in HEK-293 cells in a dose-dependent manner (up to 10 µM) in vitro and alleviate heart remodeling and functional damage in a MI (myocardial infarction) model in mice in vivo (75/mg/kg/daily i.p.).

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

Di, R., et al. 2012. Biochem. J.441, 199.Pearce, L.R., et al. 2010. Biochem. J.431, 245.

Packaging

Packaged under inert gas

10 mg in Glass bottle

Reconstitution

Following reconstitution, aliquot and freeze (-20°C.) Stock solutions are stable for up to 6 months at -20°C.

Warning

Toxicity: Standard Handling (A)