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S6 Kinase Ribosomal Protein S6 Kinase

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S6 Kinase Inhibitors (5)

water-soluble

Cat.No. Product Name Information Product Citations Customer Reviews
S2843 BI-D1870 BI-D1870 is an ATP-competitive inhibitor of ribosomal S6 for RSK1, RSK2, RSK3 and RSK4 with IC50 of 31 nM, 24 nM, 18 nM and 15 nM, respectively.
S1582 H 89 2HCl H 89 2HCl is a mutiple-targeted inhibitor for S6K1, MSK1, PKA, ROCKII, PKBα and MAPKAP-K1b with IC50 of 80 nM, 120 nM, 135 nM, 270 nM, 2600 nM and 2800 nM, respectively.
S2163 PF-4708671 PF-4708671 is a cell-permeable inhibitor of p70 ribosomal S6 kinase (S6K1 isoform) with Ki of 20 nM and IC50 of 160 nM.
S7064 FMK FMK is a potent, highly specific and irreversible inhibitor of p90 ribosomal protein S6 kinase RSK1and RSK2.
S1558 AT7867 AT7867 is a potent ATP-competitive inhibitor of Akt1/2/3 and S6K with IC50 of 32 nM/17 n/47 nM and 85 nM, respectively.
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All S6 Kinase Inhibitors

The 70 kDa ribosomal protein S6 kinase (p70 S6K) is a serine/threonine kinase. There are two highly homologous members in S6K family, which are named as S6K1 and S6K2, respectively. Both S6Ks belong to the AGC family of serine/threonine kinases and they could be activated in response to many stimulus, like growth factors, insulin and cytokines. In turn, S6Ks phosphorylate its substrates including the ribosomal protein S6, elF4B, and SKAR. It was found that the activity of S6Ks could be controlled by mammalian target of rapamycin (mTOR) [2]. And then, direct phosphorylation of S6K1 by mTOR was confirmed [3; 4]. Therefore, the activity of S6K presented sensitive to rapamycin [8]. However, the sensitivity of S6Ks to rapamycin was found always changing. S6Ks became insensitive to rapamycin when the site T412 was phosphorylated [9]. Until recently, raptor has been proved to be responsible for T412 phosphorylation [6]. Besides, S6K−/− animals showed short-lived and were much smaller than wild type animals. A study suggested that this phenomenon was due to the control of S6K on cell growth rather than proliferation [5]. To date, S6Ks are also related to many serious diseases. For example, S6K1 showed overexpression in breast cancer patients [1]. With the understanding of the importance of S6K in human diseases, the demand for S6K-specific inhibitors increased rapidly. Fortunately, a novel inhibitor specific for S6K1, PF-4708671, was developed to facilitate the study of the functions of S6K1, at the same time, and S6K2 [7].

References

[1] Barlund M, Monni O, Kononen J, Cornelison R, Torhorst J, Sauter G, Kallioniemi O-P, Kallioniemi A. Multiple genes at 17q23 undergo amplification and overexpression in breast cancer. Cancer Res 2000;60(19):5340-5344.
[2] Brown EJ, Beal PA, Keith CT, Chen J, Shin TB, Schreiber SL. Control of p70 s6 kinase by kinase activity of FRAP in vivo. Nature 1995;377(6548):441-446.
[3] Burnett PE, Barrow RK, Cohen NA, Snyder SH, Sabatini DM. RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1. Proc Natl Acad Sci U S A 1998;95(4):1432-1437.
[4] Isotani S, Hara K, Tokunaga C, Inoue H, Avruch J, Yonezawa K. Immunopurified mammalian target of rapamycin phosphorylates and activates p70 S6 kinase alpha in vitro. J Biol Chem 1999;274(48):34493-34498.
[5] Montagne J, Stewart MJ, Stocker H, Hafen E, Kozma SC, Thomas G. Drosophila S6 kinase: a regulator of cell size. Science 1999;285(5436):2126-2129.
[6] Nojima H, Tokunaga C, Eguchi S, Oshiro N, Hidayat S, Yoshino K, Hara K, Tanaka N, Avruch J, Yonezawa K. The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif. J Biol Chem 2003;278(18):15461-15464.
[7] Pearce LR, Alton GR, Richter DT, Kath JC, Lingardo L, Chapman J, Hwang C, Alessi DR. Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1). Biochem J 2010;431(2):245-255.
[8] Price DJ, Grove JR, Calvo V, Avruch J, Bierer BE. Rapamycin-induced inhibition of the 70-kilodalton S6 protein kinase. Science 1992;257(5072):973-977.
[9] Weng QP, Kozlowski M, Belham C, Zhang A, Comb MJ, Avruch J. Regulation of the p70 S6 kinase by phosphorylation in vivo. Analysis using site-specific anti-phosphopeptide antibodies. J Biol Chem 1998;273(26):16621-16629.

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