559273

S6K1 Inhibitor, PF-4708671

The S6K1 Inhibitor, PF-4708671 controls the biological activity of S6K1. This small molecule/inhibitor is primarily used for Cancer applications.

• Synonym(s): S6K1 Inhibitor, PF-4708671, (2-((4-(5-Ethylpyrimidin-4-yl)piperazin-1-yl)methyl)-5-(trifluoromethyl)-1H-benzo[d]imidazole, p70 Ribosomal S6 Kinase 1 Inhibitor
• Empirical Formula (Hill Notation): C₁₉H₂₁F₃N₆
• Molecular Weight: 390.41
• MDL number: MFCD18086922
• UNSPSC Code: 12352200
• NACRES: NA.28

Properties

• Quality Level: 100
• Assay: ≥98% (HPLC)
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: off-white
• solubility: DMSO: 50 mg/mL, pale yellow
• shipped in: ambient
• storage temp.: 2-8°C

Description

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 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.).

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.

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

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

Other Notes

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

Legal Information

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

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable