S6K1 Inhibitor, PF-4708671-Calbiochem

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一般描述

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 ?M, respectively, against RSK1, RSK2, and S6K2; ≤27% inhibition of the rest at 1 ?M). Shown to selectively inhibit IGF1- and PMA-stimulated S6K1 substrates phosphorylation in HEK-293 cells in a dose-dependent manner (up to 10 ?M)in vitroand alleviate heart remodeling and functional damage in a MI (myocardial infarction) model in micein vivo(75/mg/kg/daily i.p.).
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 ?M, respectively, against RSK1, RSK2, and S6K2; ≤27% inhibition of the rest at 1 ?M) and 10 lipid kinases (≤6% inhibition at 10 ?M). Inhibits IGF1-induced phosphorylation of cellular S6K1 substrates S6 (Ser^235/236and 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 Ser¹³³and GSK3α/β Ser²¹/ Ser⁹, respectively) upon PMA stimulation even at concentrations as high as 10 ?M. 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 micein 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.

包装

10 mg in Glass bottle
Packaged under inert gas

警告

Toxicity: Standard Handling (A)

重悬

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

其他说明

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

法律信息

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

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