Login Register Cart 0
Mini-Review Article

70 kDa核糖体蛋白S6激酶(P70S6K)抑制剂作为治疗肥胖、2型糖尿病和癌症的有效工具的研究进展

卷 27, 期 28, 2020

页: [4699 - 4719] 页: 21

弟呕挨: 10.2174/0929867327666200114113139

价格: $65

摘要

目前 ,如肥胖、Ⅱ型糖尿病和癌症等疾病带来的严重健康问题与mTOR通路密切相关。70 kDa核糖体蛋白S6激酶(p70S6K)是mTOR的重要下游效应因子，介导蛋白合成、RNA加工、葡萄糖稳态、细胞生长和凋亡。抑制p70S6K的功能可以降低肥胖的风险，有助于治疗血脂异常，提高胰岛素敏感性，延长哺乳动物的寿命。因此，p70S6K成为治疗这些疾病的潜在靶点。目前，除了辉瑞公司开发的第一个p70S6K特异性抑制剂PF-4708671和礼来公司开发的LY2584702外，所有p70S6K抑制剂均处于临床前研究阶段。本文简要介绍了p70S6K的概况，并对其近年来的抑制剂进行了综述，主要将其分为两类:天然化合物和合成化合物。特别强调了它们的抑制活性、构效关系(SARs)和机制。

关键词: p70S6K，潜在靶标、疾病、抑制剂、活性、构效关系。

« Previous Next »
[1]
Peterson, R.T.; Schreiber, S.L. Kinase phosphorylation: Keeping it all in the family. Curr. Biol., 1999, 9(14), R521-R524.
[http://dx.doi.org/10.1016/S0960-9822(99)80326-1] [PMID: 10421571]
[2]
Ziegler, W.H.; Parekh, D.B.; Le Good, J.A.; Whelan, R.D.H.; Kelly, J.J.; Frech, M.; Hemmings, B.A.; Parker, P.J. Rapamycin sensitive phosphorylation of PKC on a carboxy-terminal site by an atypical PKC complex. Curr. Biol., 1999, 9(10), 522-529.
[http://dx.doi.org/10.1016/S0960-9822(99)80236-X] [PMID: 10339425]
[3]
Brazil, D.P.; Hemmings, B.A. Ten years of protein kinase B signalling: a hard Akt to follow. Trends Biochem. Sci., 2001, 26(11), 657-664.
[http://dx.doi.org/10.1016/S0968-0004(01)01958-2] [PMID: 11701324]
[4]
Coffer, P.J.; Woodgett, J.R. Molecular cloning and characterisation of a novel putative protein-serine kinase related to the cAMP-dependent and protein kinase C families. Eur. J. Biochem., 1991, 201(2), 475-481.
[http://dx.doi.org/10.1111/j.1432-1033.1991.tb16305.x] [PMID: 1718748]
[5]
Grove, J.R.; Banerjee, P.; Balasubramanyam, A.; Coffer, P.J.; Price, D.J.; Avruch, J.; Woodgett, J.R. Cloning and expression of two human p70 S6 kinase polypeptides differing only at their amino termini. Mol. Cell. Biol., 1991, 11(11), 5541-5550.
[http://dx.doi.org/10.1128/MCB.11.11.5541] [PMID: 1922062]
[6]
Gout, I.; Minami, T.; Hara, K.; Tsujishita, Y.; Filonenko, V.; Waterfield, M.D.; Yonezawa, K. Molecular cloning and characterization of a novel p70 S6 kinase, p70 S6 kinase beta containing a proline-rich region. J. Biol. Chem., 1998, 273(46), 30061-30064.
[http://dx.doi.org/10.1074/jbc.273.46.30061] [PMID: 9804755]
[7]
Proud, C.G. Regulation of mammalian translation factors by nutrients. Eur. J. Biochem., 2002, 269(22), 5338-5349.
[http://dx.doi.org/10.1046/j.1432-1033.2002.03292.x] [PMID: 12423332]
[8]
Schmelzle, T.; Hall, M.N. TOR, a central controller of cell growth. Cell, 2000, 103(2), 253-262.
[http://dx.doi.org/10.1016/S0092-8674(00)00117-3] [PMID: 11057898]
[9]
Gassaway, B.M.; Petersen, M.C.; Surovtseva, Y.V.; Barber, K.W.; Sheetz, J.B.; Aerni, H.R.; Merkel, J.S.; Samuel, V.T.; Shulman, G.I.; Rinehart, J. PKCε contributes to lipid-induced insulin resistance through cross talk with p70S6K and through previously unknown regulators of insulin signaling. Proc. Natl. Acad. Sci. USA, 2018, 115(38), E8996-E9005.
[http://dx.doi.org/10.1073/pnas.1804379115] [PMID: 30181290]
[10]
Csibi, A.; Lee, G.; Yoon, S-O.; Tong, H.; Ilter, D.; Elia, I.; Fendt, S-M.; Roberts, T.M.; Blenis, J. The mTORC1/S6K1 pathway regulates glutamine metabolism through the eIF4B-dependent control of c-Myc translation. Curr. Biol., 2014, 24(19), 2274-2280.
[http://dx.doi.org/10.1016/j.cub.2014.08.007] [PMID: 25220053]
[11]
Wang, X.; Li, W.; Williams, M.; Terada, N.; Alessi, D.R.; Proud, C.G. Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase. EMBO J., 2001, 20(16), 4370-4379.
[http://dx.doi.org/10.1093/emboj/20.16.4370] [PMID: 11500364]
[12]
Harada, H.; Andersen, J.S.; Mann, M.; Terada, N.; Korsmeyer, S.J. p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD. Proc. Natl. Acad. Sci. USA, 2001, 98(17), 9666-9670.
[http://dx.doi.org/10.1073/pnas.171301998] [PMID: 11493700]
[13]
Bailey, J.; Tyson-Capper, A.J.; Gilmore, K.; Robson, S.C.; Europe-Finner, G.N. Identification of human myometrial target genes of the cAMP pathway: the role of cAMP-response element binding (CREB) and modulator (CREMalpha and CREMtau2alpha) proteins. J. Mol. Endocrinol., 2005, 34(1), 1-17.
[http://dx.doi.org/10.1677/jme.1.01594] [PMID: 15691874]
[14]
Ruvinsky, I.; Meyuhas, O. Ribosomal protein S6 phosphorylation: from protein synthesis to cell size. Trends Biochem. Sci., 2006, 31(6), 342-348.
[http://dx.doi.org/10.1016/j.tibs.2006.04.003] [PMID: 16679021]
[15]
Um, S.H.; Frigerio, F.; Watanabe, M.; Picard, F.; Joaquin, M.; Sticker, M.; Fumagalli, S.; Allegrini, P.R.; Kozma, S.C.; Auwerx, J.; Thomas, G. Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Nature, 2004, 431(7007), 485-485.
[http://dx.doi.org/10.1038/nature02979]
[16]
Berven, L.A.; Willard, F.S.; Crouch, M.F. Role of the p70(S6K) pathway in regulating the actin cytoskeleton and cell migration. Exp. Cell Res., 2004, 296(2), 183-195.
[http://dx.doi.org/10.1016/j.yexcr.2003.12.032] [PMID: 15149849]
[17]
Weng, Q.P.; Andrabi, K.; Kozlowski, M.T.; Grove, J.R.; Avruch, J. Multiple independent inputs are required for activation of the p70 S6 kinase. Mol. Cell. Biol., 1995, 15(5), 2333-2340.
[http://dx.doi.org/10.1128/MCB.15.5.2333] [PMID: 7739516]
[18]
Cheatham, L.; Monfar, M.; Chou, M.M.; Blenis, J. Structural and functional analysis of pp70S6k. Proc. Natl. Acad. Sci. USA, 1995, 92(25), 11696-11700.
[http://dx.doi.org/10.1073/pnas.92.25.11696] [PMID: 8524831]
[19]
Dennis, P.B.; Pullen, N.; Kozma, S.C.; Thomas, G. The principal rapamycin-sensitive p70(s6k) phosphorylation sites, T-229 and T-389, are differentially regulated by rapamycin-insensitive kinase kinases. Mol. Cell. Biol., 1996, 16(11), 6242-6251.
[http://dx.doi.org/10.1128/MCB.16.11.6242] [PMID: 8887654]
[20]
Pearson, R.B.; Dennis, P.B.; Han, J.W.; Williamson, N.A.; Kozma, S.C.; Wettenhall, R.E.H.; Thomas, G. The principal target of rapamycin-induced p70s6k inactivation is a novel phosphorylation site within a conserved hydrophobic domain. EMBO J., 1995, 14(21), 5279-5287.
[http://dx.doi.org/10.1002/j.1460-2075.1995.tb00212.x] [PMID: 7489717]
[21]
Weng, Q.P.; Andrabi, K.; Klippel, A.; Kozlowski, M.T.; Williams, L.T.; Avruch, J. Phosphatidylinositol 3-kinase signals activation of p70 S6 kinase in situ through site specific p70 phosphorylation. Proc. Natl. Acad. Sci. USA, 1995, 92(12), 5744-5748.
[http://dx.doi.org/10.1073/pnas.92.12.5744] [PMID: 7777579]
[22]
Kannan, N.; Haste, N.; Taylor, S.S.; Neuwald, A.F. The hallmark of AGC kinase functional divergence is its C-terminal tail, a cis-acting regulatory module. Proc. Natl. Acad. Sci. USA, 2007, 104(4), 1272-1277.
[http://dx.doi.org/10.1073/pnas.0610251104] [PMID: 17227859]
[23]
Ferrari, S.; Bannwarth, W.; Morley, S.J.; Totty, N.F.; Thomas, G. Activation of p70s6k is associated with phosphorylation of four clustered sites displaying Ser/Thr-Pro motifs. Proc. Natl. Acad. Sci. USA, 1992, 89(15), 7282-7286.
[http://dx.doi.org/10.1073/pnas.89.15.7282] [PMID: 1496022]
[24]
Hauge, C.; Antal, T.L.; Hirschberg, D.; Doehn, U.; Thorup, K.; Idrissova, L.; Hansen, K.; Jensen, O.N.; Jørgensen, T.J.; Biondi, R.M.; Frödin, M. Mechanism for activation of the growth factor-activated AGC kinases by turn motif phosphorylation. EMBO J., 2007, 26(9), 2251-2261.
[http://dx.doi.org/10.1038/sj.emboj.7601682] [PMID: 17446865]
[25]
Keshwani, M.M.; von Daake, S.; Newton, A.C.; Harris, T.K.; Taylor, S.S. Hydrophobic motif phosphorylation is not required for activation loop phosphorylation of p70 ribosomal protein S6 kinase 1 (S6K1). J. Biol. Chem., 2011, 286(26), 23552-23558.
[http://dx.doi.org/10.1074/jbc.M111.258004] [PMID: 21561857]
[26]
Keranen, L.M.; Dutil, E.M.; Newton, A.C. Protein kinase C is regulated in vivo by three functionally distinct phosphorylations. Curr. Biol., 1995, 5(12), 1394-1403.
[http://dx.doi.org/10.1016/S0960-9822(95)00277-6] [PMID: 8749392]
[27]
Bandarage, U.; Hare, B.; Parsons, J.; Pham, L.; Marhefka, C.; Bemis, G.; Tang, Q.; Moody, C.S.; Rodems, S.; Shah, S.; Adams, C.; Bravo, J.; Charonnet, E.; Savic, V.; Come, J.H.; Green, J. 4-(Benzimidazol-2-yl)-1,2,5-oxadiazol-3-ylamine derivatives: potent and selective p70S6 kinase inhibitors. Bioorg. Med. Chem. Lett., 2009, 19(17), 5191-5194.
[http://dx.doi.org/10.1016/j.bmcl.2009.07.022] [PMID: 19632115]
[28]
Wenlei, B.; Xiyan, H.; Xu, Z.; Yan, L.; Yuhao, C.; Yanfeng, W.; Zhigang, W. Molecular Characterization and Expression Analysis of Ribosomal Protein S6 Gene in the Cashmere Goat (Capra hircus). Asian-Australas. J. Anim. Sci., 2013, 26(11), 1644-1650.
[http://dx.doi.org/10.5713/ajas.2013.13157] [PMID: 25049753]
[29]
Raught, B.; Peiretti, F.; Gingras, A.C.; Livingstone, M.; Shahbazian, D.; Mayeur, G.L.; Polakiewicz, R.D.; Sonenberg, N.; Hershey, J.W.B. Phosphorylation of eucaryotic translation initiation factor 4B Ser422 is modulated by S6 kinases. EMBO J., 2004, 23(8), 1761-1769.
[http://dx.doi.org/10.1038/sj.emboj.7600193] [PMID: 15071500]
[30]
Montero, H.; Pérez-Gil, G.; Sampieri, C.L. Eukaryotic initiation factor 4A (eIF4A) during viral infections. Virus Genes, 2019, 55(3), 267-273.
[http://dx.doi.org/10.1007/s11262-019-01641-7] [PMID: 30796742]
[31]
Matsuhashi, S.; Manirujjaman, M.; Hamajima, H.; Ozaki, I. Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions. Int. J. Mol. Sci., 2019, 20(9) E2304
[http://dx.doi.org/10.3390/ijms20092304] [PMID: 31075975]
[32]
Wang, B.; Li, Y. Evidence for the direct involvement of βTrCP in Gli3 protein processing. Proc. Natl. Acad. Sci. USA, 2006, 103(1), 33-38.
[http://dx.doi.org/10.1073/pnas.0509927103] [PMID: 16371461]
[33]
Dorrello, N.V.; Peschiaroli, A.; Guardavaccaro, D.; Colburn, N.H.; Sherman, N.E.; Pagano, M. S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth. Science, 2006, 314(5798), 467-471.
[http://dx.doi.org/10.1126/science.1130276] [PMID: 17053147]
[34]
Bian, C-X.; Shi, Z.; Meng, Q.; Jiang, Y.; Liu, L-Z.; Jiang, B-H. P70S6K 1 regulation of angiogenesis through VEGF and HIF-1alpha expression. Biochem. Biophys. Res. Commun., 2010, 398(3), 395-399.
[http://dx.doi.org/10.1016/j.bbrc.2010.06.080] [PMID: 20599538]
[35]
Skinner, H.D.; Zheng, J.Z.; Fang, J.; Agani, F.; Jiang, B.H. Vascular endothelial growth factor transcriptional activation is mediated by hypoxia-inducible factor 1alpha, HDM2, and p70S6K1 in response to phosphatidylinositol 3-kinase/AKT signaling. J. Biol. Chem., 2004, 279(44), 45643-45651.
[http://dx.doi.org/10.1074/jbc.M404097200] [PMID: 15337760]
[36]
Ben-Hur, V.; Denichenko, P.; Siegfried, Z.; Maimon, A.; Krainer, A.; Davidson, B.; Karni, R. S6K1 alternative splicing modulates its oncogenic activity and regulates mTORC1. Cell Rep., 2013, 3(1), 103-115.
[http://dx.doi.org/10.1016/j.celrep.2012.11.020] [PMID: 23273915]
[37]
Heitman, J.; Movva, N.R.; Hall, M.N. Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science, 1991, 253(5022), 905-909.
[http://dx.doi.org/10.1126/science.1715094] [PMID: 1715094]
[38]
Jiang, K.; Chen, H.; Tang, K.; Guan, W.; Zhou, H.; Guo, X.; Chen, Z.; Ye, Z.; Xu, H. Puerarin inhibits bladder cancer cell proliferation through the mTOR/p70S6K signaling pathway. Oncol. Lett., 2018, 15(1), 167-174.
[PMID: 29375709]
[39]
Rosa, R.; Damiano, V.; Nappi, L.; Formisano, L.; Massari, F.; Scarpa, A.; Martignoni, G.; Bianco, R.; Tortora, G. Angiogenic and signalling proteins correlate with sensitivity to sequential treatment in renal cell cancer. Br. J. Cancer, 2013, 109(3), 686-693.
[http://dx.doi.org/10.1038/bjc.2013.360] [PMID: 23839492]
[40]
Li, S-H.; Chen, C-H.; Lu, H-I.; Huang, W-T.; Tien, W-Y.; Lan, Y-C.; Lee, C-C.; Chen, Y-H.; Huang, H-Y.; Chang, A.Y.W.; Lin, W-C. Phosphorylated p70S6K expression is an independent prognosticator for patients with esophageal squamous cell carcinoma. Surgery, 2015, 157(3), 570-580.
[http://dx.doi.org/10.1016/j.surg.2014.10.014] [PMID: 25726316]
[41]
Maruani, D.M.; Spiegel, T.N.; Harris, E.N.; Shachter, A.S.; Unger, H.A.; Herrero-González, S.; Holz, M.K. Estrogenic regulation of S6K1 expression creates a positive regulatory loop in control of breast cancer cell proliferation. Oncogene, 2012, 31(49), 5073-5080.
[http://dx.doi.org/10.1038/onc.2011.657] [PMID: 22286763]
[42]
Pérez-Tenorio, G.; Karlsson, E.; Waltersson, M.A.; Olsson, B.; Holmlund, B.; Nordenskjöld, B.; Fornander, T.; Skoog, L.; Stål, O. Clinical potential of the mTOR targets S6K1 and S6K2 in breast cancer. Breast Cancer Res. Treat., 2011, 128(3), 713-723.
[http://dx.doi.org/10.1007/s10549-010-1058-x] [PMID: 20953835]
[43]
Holz, M.K. The role of S6K1 in ER-positive breast cancer. Cell Cycle, 2012, 11(17), 3159-3165.
[http://dx.doi.org/10.4161/cc.21194] [PMID: 22895181]
[44]
Longo, M.; Zatterale, F.; Naderi, J.; Parrillo, L.; Formisano, P.; Raciti, G.A.; Beguinot, F.; Miele, C. Adipose Tissue Dysfunction as Determinant of Obesity-Associated Metabolic Complications. Int. J. Mol. Sci., 2019, 20(9) E2358
[http://dx.doi.org/10.3390/ijms20092358] [PMID: 31085992]
[45]
McLaughlin, T.; Craig, C.; Liu, L-F.; Perelman, D.; Allister, C.; Spielman, D.; Cushman, S.W. Adipose cell size and regional fat deposition as predictors of metabolic response to overfeeding in insulin-resistant and insulin-sensitive humans. Diabetes, 2016, 65(5), 1245-1254.
[http://dx.doi.org/10.2337/db15-1213] [PMID: 26884438]
[46]
Birsoy, K.; Festuccia, W.T.; Laplante, M. A comparative perspective on lipid storage in animals. J. Cell Sci., 2013, 126(Pt 7), 1541-1552.
[http://dx.doi.org/10.1242/jcs.104992] [PMID: 23658371]
[47]
Um, S.H.; Frigerio, F.; Watanabe, M.; Picard, F.; Joaquin, M.; Sticker, M.; Fumagalli, S.; Allegrini, P.R.; Kozma, S.C.; Auwerx, J.; Thomas, G. Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Nature, 2004, 431(7005), 200-205.
[http://dx.doi.org/10.1038/nature02866] [PMID: 15306821]
[48]
Tzatsos, A.; Kandror, K.V. Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation. Mol. Cell. Biol., 2006, 26(1), 63-76.
[http://dx.doi.org/10.1128/MCB.26.1.63-76.2006] [PMID: 16354680]
[49]
Chung, J.; Grammer, T.C.; Lemon, K.P.; Kazlauskas, A.; Blenis, J. PDGF- and insulin-dependent pp70S6k activation mediated by phosphatidylinositol-3-OH kinase. Nature, 1994, 370(6484), 71-75.
[http://dx.doi.org/10.1038/370071a0] [PMID: 8015612]
[50]
Cross, D.A.E.; Alessi, D.R.; Cohen, P.; Andjelkovich, M.; Hemmings, B.A. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature, 1995, 378(6559), 785-789.
[http://dx.doi.org/10.1038/378785a0] [PMID: 8524413]
[51]
Harrington, L.S.; Findlay, G.M.; Gray, A.; Tolkacheva, T.; Wigfield, S.; Rebholz, H.; Barnett, J.; Leslie, N.R.; Cheng, S.; Shepherd, P.R.; Gout, I.; Downes, C.P.; Lamb, R.F. The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J. Cell Biol., 2004, 166(2), 213-223.
[http://dx.doi.org/10.1083/jcb.200403069] [PMID: 15249583]
[52]
Piedfer, M.; Bouchet, S.; Tang, R.; Billard, C.; Dauzonne, D.; Bauvois, B. p70S6 kinase is a target of the novel proteasome inhibitor 3,3′-diamino-4′-methoxyflavone during apoptosis in human myeloid tumor cells. Biochim. Biophys. Acta, 2013, 1833(6), 1316-1328.
[http://dx.doi.org/10.1016/j.bbamcr.2013.02.016] [PMID: 23481040]
[53]
Arai, Y.; Watanabe, S.; Kimira, M.; Shimoi, K.; Mochizuki, R.; Kinae, N. Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration. J. Nutr., 2000, 130(9), 2243-2250.
[http://dx.doi.org/10.1093/jn/130.9.2243] [PMID: 10958819]
[54]
Syed, D.N.; Afaq, F.; Maddodi, N.; Johnson, J.J.; Sarfaraz, S.; Ahmad, A.; Setaluri, V.; Mukhtar, H. Inhibition of human melanoma cell growth by the dietary flavonoid fisetin is associated with disruption of Wnt/β-catenin signaling and decreased Mitf levels. J. Invest. Dermatol., 2011, 131(6), 1291-1299.
[http://dx.doi.org/10.1038/jid.2011.6] [PMID: 21346776]
[55]
Sechi, M.; Lall, R.K.; Afolabi, S.O.; Singh, A.; Joshi, D.C.; Chiu, S-Y.; Mukhtar, H.; Syed, D.N. Fisetin targets YB-1/RSK axis independent of its effect on ERK signaling: insights from in vitro and in vivo melanoma models. Sci. Rep., 2018, 8(1), 15726.
[http://dx.doi.org/10.1038/s41598-018-33879-w] [PMID: 30356079]
[56]
Syed, D.N.; Chamcheu, J-C.; Khan, M.I.; Sechi, M.; Lall, R.K.; Adhami, V.M.; Mukhtar, H. Fisetin inhibits human melanoma cell growth through direct binding to p70S6K and mTOR: findings from 3-D melanoma skin equivalents and computational modeling. Biochem. Pharmacol., 2014, 89(3), 349-360.
[http://dx.doi.org/10.1016/j.bcp.2014.03.007] [PMID: 24675012]
[57]
Jang, M.; Cai, L.; Udeani, G.O.; Slowing, K.V.; Thomas, C.F.; Beecher, C.W.W.; Fong, H.H.S.; Farnsworth, N.R.; Kinghorn, A.D.; Mehta, R.G.; Moon, R.C.; Pezzuto, J.M. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science, 1997, 275(5297), 218-220.
[http://dx.doi.org/10.1126/science.275.5297.218] [PMID: 8985016]
[58]
Alkhalaf, M. Resveratrol-induced apoptosis is associated with activation of p53 and inhibition of protein translation in T47D human breast cancer cells. Pharmacology, 2007, 80(2-3), 134-143.
[http://dx.doi.org/10.1159/000103253] [PMID: 17534123]
[59]
Thiyagarajan, V.; Lee, K-W.; Leong, M.K.; Weng, C-F. Potential natural mTOR inhibitors screened by in silico approach and suppress hepatic stellate cells activation. J. Biomol. Struct. Dyn., 2018, 36(16), 4220-4234.
[http://dx.doi.org/10.1080/07391102.2017.1411295] [PMID: 29183268]
[60]
Yu, C-C.; Chiang, P-C.; Lu, P-H.; Kuo, M-T.; Wen, W-C.; Chen, P.; Guh, J-H. Antroquinonol, a natural ubiquinone derivative, induces a cross talk between apoptosis, autophagy and senescence in human pancreatic carcinoma cells. J. Nutr. Biochem., 2012, 23(8), 900-907.
[http://dx.doi.org/10.1016/j.jnutbio.2011.04.015] [PMID: 21840189]
[61]
Lee, M.S.; Cha, E.Y.; Sul, J.Y.; Song, I.S.; Kim, J.Y. Chrysophanic acid blocks proliferation of colon cancer cells by inhibiting EGFR/mTOR pathway. Phytother. Res., 2011, 25(6), 833-837.
[http://dx.doi.org/10.1002/ptr.3323] [PMID: 21089180]
[62]
Zhang, B.; Huang, H.; Xie, J.; Xu, C.; Chen, M.; Wang, C.; Yang, A.; Yin, Q. Cucurmosin induces apoptosis of BxPC-3 human pancreatic cancer cells via inactivation of the EGFR signaling pathway. Oncol. Rep., 2012, 27(3), 891-897.
[PMID: 22139427]
[63]
Jeong, J-H.; Jeong, Y-J.; Cho, H-J.; Shin, J-M.; Kang, J-H.; Park, K-K.; Park, Y-Y.; Chung, I-K.; Chang, H-W.; Magae, J.; Kang, S-S.; Chang, Y-C. Ascochlorin inhibits growth factor-induced HIF-1α activation and tumor-angiogenesis through the suppression of EGFR/ERK/p70S6K signaling pathway in human cervical carcinoma cells. J. Cell. Biochem., 2012, 113(4), 1302-1313.
[http://dx.doi.org/10.1002/jcb.24001] [PMID: 22109717]
[64]
Shin, J-M.; Jeong, Y-J.; Cho, H-J.; Magae, J.; Bae, Y-S.; Chang, Y-C. Suppression of c-Myc induces apoptosis via an AMPK/mTOR-dependent pathway by 4-O-methyl ascochlorin in leukemia cells (vol 21, pg 657, 2016). Apoptosis, 2016, 21(5), 669-670.
[http://dx.doi.org/10.1007/s10495-016-1239-0] [PMID: 27030036]
[65]
Pearce, L.R.; Alton, G.R.; Richter, D.T.; Kath, J.C.; Lingardo, L.; Chapman, J.; Hwang, C.; Alessi, D.R. Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1). Biochem. J., 2010, 431(2), 245-255.
[http://dx.doi.org/10.1042/BJ20101024] [PMID: 20704563]
[66]
Holz, M.K.; Blenis, J. Identification of S6 kinase 1 as a novel mammalian target of rapamycin (mTOR)-phosphorylating kinase. J. Biol. Chem., 2005, 280(28), 26089-26093.
[http://dx.doi.org/10.1074/jbc.M504045200] [PMID: 15905173]
[67]
Treins, C.; Warne, P.H.; Magnuson, M.A.; Pende, M.; Downward, J. Rictor is a novel target of p70 S6 kinase-1. Oncogene, 2010, 29(7), 1003-1016.
[http://dx.doi.org/10.1038/onc.2009.401] [PMID: 19935711]
[68]
Wang, J.; Zhong, C.; Wang, F.; Qu, F.; Ding, J. Crystal structures of S6K1 provide insights into the regulation mechanism of S6K1 by the hydrophobic motif. Biochem. J., 2013, 454(1), 39-47.
[http://dx.doi.org/10.1042/BJ20121863] [PMID: 23731517]
[69]
Sunami, T.; Byrne, N.; Diehl, R.E.; Funabashi, K.; Hall, D.L.; Ikuta, M.; Patel, S.B.; Shipman, J.M.; Smith, R.F.; Takahashi, I.; Zugay-Murphy, J.; Iwasawa, Y.; Lumb, K.J.; Munshi, S.K.; Sharma, S. Structural basis of human p70 ribosomal S6 kinase-1 regulation by activation loop phosphorylation. J. Biol. Chem., 2010, 285(7), 4587-4594.
[http://dx.doi.org/10.1074/jbc.M109.040667] [PMID: 19864428]
[70]
Qiu, Z-X.; Sun, R-F.; Mo, X-M.; Li, W-M. The p70S6K Specific Inhibitor PF-4708671 Impedes Non-Small Cell Lung Cancer Growth. PLoS One, 2016, 11(1) e0147185
[http://dx.doi.org/10.1371/journal.pone.0147185] [PMID: 26771549]
[71]
Shum, M.; Bellmann, K.; St-Pierre, P.; Marette, A. Pharmacological inhibition of S6K1 increases glucose metabolism and Akt signalling in vitro and in diet-induced obese mice. Diabetologia, 2016, 59(3), 592-603.
[http://dx.doi.org/10.1007/s00125-015-3839-6] [PMID: 26733005]
[72]
Shum, M.; Houde, V.P.; Bellemare, V.; Junges Moreira, R.; Bellmann, K.; St-Pierre, P.; Viollet, B.; Foretz, M.; Marette, A. Inhibition of mitochondrial complex 1 by the S6K1 inhibitor PF-4708671 partly contributes to its glucose metabolic effects in muscle and liver cells. J. Biol. Chem., 2019, 294(32), 12250-12260.
[http://dx.doi.org/10.1074/jbc.RA119.008488] [PMID: 31243102]
[73]
Lee-Fruman, K.K.; Kuo, C.J.; Lippincott, J.; Terada, N.; Blenis, J. Characterization of S6K2, a novel kinase homologous to S6K1. Oncogene, 1999, 18(36), 5108-5114.
[http://dx.doi.org/10.1038/sj.onc.1202894] [PMID: 10490847]
[74]
Bradshaw, D.; Hill, C.H.; Nixon, J.S.; Wilkinson, S.E. Therapeutic potential of protein kinase C inhibitors. Agents Actions, 1993, 38(1-2), 135-147.
[http://dx.doi.org/10.1007/BF02027225] [PMID: 8480534]
[75]
Roberts, N.A.; Marber, M.S.; Avkiran, M. Specificity of action of bisindolylmaleimide protein kinase C inhibitors: do they inhibit the 70kDa ribosomal S6 kinase in cardiac myocytes? Biochem. Pharmacol., 2004, 68(10), 1923-1928.
[http://dx.doi.org/10.1016/j.bcp.2004.07.040] [PMID: 15476663]
[76]
Alessi, D.R. The protein kinase C inhibitors Ro 318220 and GF 109203X are equally potent inhibitors of MAPKAP kinase-1beta (Rsk-2) and p70 S6 kinase. FEBS Lett., 1997, 402(2-3), 121-123.
[http://dx.doi.org/10.1016/S0014-5793(96)01510-4] [PMID: 9037179]
[77]
Marmy-Conus, N.; Hannan, K.M.; Pearson, R.B. Ro 31-6045, the inactive analogue of the protein kinase C inhibitor Ro 31-8220, blocks in vivo activation of p70(s6k)/p85(s6k): implications for the analysis of S6K signalling. FEBS Lett., 2002, 519(1-3), 135-140.
[http://dx.doi.org/10.1016/S0014-5793(02)02738-2] [PMID: 12023032]
[78]
Davies, S.P.; Reddy, H.; Caivano, M.; Cohen, P. Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem. J., 2000, 351(Pt 1), 95-105.
[http://dx.doi.org/10.1042/bj3510095] [PMID: 10998351]
[79]
Pinner, S.; Sahai, E. PDK1 regulates cancer cell motility by antagonising inhibition of ROCK1 by RhoE. Nat. Cell Biol., 2008, 10(2), 127-137.
[http://dx.doi.org/10.1038/ncb1675] [PMID: 18204440]
[80]
Couty, S.; Westwood, I.M.; Kalusa, A.; Cano, C.; Travers, J.; Boxall, K.; Chow, C.L.; Burns, S.; Schmitt, J.; Pickard, L.; Barillari, C.; McAndrew, P.C.; Clarke, P.A.; Linardopoulos, S.; Griffin, R.J.; Aherne, G.W.; Raynaud, F.I.; Workman, P.; Jones, K.; van Montfort, R.L.M. The discovery of potent ribosomal S6 kinase inhibitors by high-throughput screening and structure-guided drug design. Oncotarget, 2013, 4(10), 1647-1661.
[http://dx.doi.org/10.18632/oncotarget.1255] [PMID: 24072592]
[81]
Stavenger, R.A.; Cui, H.; Dowdell, S.E.; Franz, R.G.; Gaitanopoulos, D.E.; Goodman, K.B.; Hilfiker, M.A.; Ivy, R.L.; Leber, J.D.; Marino, J.P., Jr; Oh, H.J.; Viet, A.Q.; Xu, W.; Ye, G.; Zhang, D.; Zhao, Y.; Jolivette, L.J.; Head, M.S.; Semus, S.F.; Elkins, P.A.; Kirkpatrick, R.B.; Dul, E.; Khandekar, S.S.; Yi, T.; Jung, D.K.; Wright, L.L.; Smith, G.K.; Behm, D.J.; Doe, C.P.; Bentley, R.; Chen, Z.X.; Hu, E.; Lee, D. Discovery of aminofurazan-azabenzimidazoles as inhibitors of Rho-kinase with high kinase selectivity and antihypertensive activity. J. Med. Chem., 2007, 50(1), 2-5.
[http://dx.doi.org/10.1021/jm060873p] [PMID: 17201404]
[82]
Bussenius, J.; Anand, N.K.; Blazey, C.M.; Bowles, O.J.; Bannen, L.C.; Chan, D.S.M.; Chen, B.; Co, E.W.; Costanzo, S.; DeFina, S.C.; Dubenko, L.; Engst, S.; Franzini, M.; Huang, P.; Jammalamadaka, V.; Khoury, R.G.; Kim, M.H.; Klein, R.R.; Laird, D.; Le, D.T.; Mac, M.B.; Matthews, D.J.; Markby, D.; Miller, N.; Nuss, J.M.; Parks, J.J.; Tsang, T.H.; Tsuhako, A.L.; Wang, Y.; Xu, W.; Rice, K.D. Design and evaluation of a series of pyrazolopyrimidines as p70S6K inhibitors. Bioorg. Med. Chem. Lett., 2012, 22(6), 2283-2286.
[http://dx.doi.org/10.1016/j.bmcl.2012.01.105] [PMID: 22342124]
[83]
Tolcher, A.; Goldman, J.; Patnaik, A.; Papadopoulos, K.P.; Westwood, P.; Kelly, C.S.; Bumgardner, W.; Sams, L.; Geeganage, S.; Wang, T.; Capen, A.R.; Huang, J.; Joseph, S.; Miller, J.; Benhadji, K.A.; Brail, L.H.; Rosen, L.S. A phase I trial of LY2584702 tosylate, a p70 S6 kinase inhibitor, in patients with advanced solid tumours. Eur. J. Cancer, 2014, 50(5), 867-875.
[http://dx.doi.org/10.1016/j.ejca.2013.11.039] [PMID: 24440085]
[84]
Leohr, J.K.; Luffer-Atlas, D.; Luo, M.J.; DeBrota, D.J.; Green, C.; Mabry, T.E.; Suico, J.G. Serum Lipid and Protein Changes in Healthy Dyslipidemic Subjects Given a Selective Inhibitor of p70 S6 Kinase-1. J. Clin. Pharmacol., 2018, 58(4), 412-424.
[http://dx.doi.org/10.1002/jcph.1032] [PMID: 29178617]
[85]
Hollebecque, A.; Houédé, N.; Cohen, E.E.W.; Massard, C.; Italiano, A.; Westwood, P.; Bumgardner, W.; Miller, J.; Brail, L.H.; Benhadji, K.A.; Soria, J.C. A phase Ib trial of LY2584702 tosylate, a p70 S6 inhibitor, in combination with erlotinib or everolimus in patients with solid tumours. Eur. J. Cancer, 2014, 50(5), 876-884.
[http://dx.doi.org/10.1016/j.ejca.2013.12.006] [PMID: 24456794]
[86]
Qin, J.; Rajaratnam, R.; Feng, L.; Salami, J.; Barber-Rotenberg, J.S.; Domsic, J.; Reyes-Uribe, P.; Liu, H.; Dang, W.; Berger, S.L.; Villanueva, J.; Meggers, E.; Marmorstein, R. Development of organometallic S6K1 inhibitors. J. Med. Chem., 2015, 58(1), 305-314.
[http://dx.doi.org/10.1021/jm5011868] [PMID: 25356520]
[87]
Bae, E.J.; Yang, Y.M.; Kim, J.W.; Kim, S.G. Identification of a novel class of dithiolethiones that prevent hepatic insulin resistance via the adenosine monophosphate-activated protein kinase-p70 ribosomal S6 kinase-1 pathway. Hepatology, 2007, 46(3), 730-739.
[http://dx.doi.org/10.1002/hep.21769] [PMID: 17668885]
[88]
Shin, S.M.; Kim, S.G. Inhibition of arachidonic acid and iron-induced mitochondrial dysfunction and apoptosis by oltipraz and novel 1,2-dithiole-3-thione congeners. Mol. Pharmacol., 2009, 75(1), 242-253.
[http://dx.doi.org/10.1124/mol.108.051128] [PMID: 18945820]
[89]
Moore, W.R., Jr; Springman, E.; Michelotti, E. Preparation of heteroarylaryl ureas as inhibitors of protein kinases. WO2006062984A2. 2006.
[90]
Ye, P.; Kuhn, C.; Juan, M.; Sharma, R.; Connolly, B.; Alton, G.; Liu, H.; Stanton, R.; Kablaoui, N.M. Potent and selective thiophene urea-templated inhibitors of S6K. Bioorg. Med. Chem. Lett., 2011, 21(2), 849-852.
[http://dx.doi.org/10.1016/j.bmcl.2010.11.069] [PMID: 21185721]
[91]
Quastel, J.H.; Cantero, A. Inhibition of tumour growth by D-glucosamine. Nature, 1953, 171(4345), 252-254.
[http://dx.doi.org/10.1038/171252a0] [PMID: 13036842]
[92]
Bekesi, J.G.; Molnar, Z.; Winzler, R.J. Inhibitory effect of d-glucosamine and other sugar analogs on the viability and transplantability of ascites tumor cells. Cancer Res., 1969, 29(2), 353-359.
[PMID: 5765417]
[93]
Bekesi, J.G.; Winzler, R.J. Inhibitory effects of D-glucosamine on the growth of Walker 256 carcinosarcoma and on protein, RNA, and DNA synthesis. Cancer Res., 1970, 30(12), 2905-2912.
[PMID: 5494575]
[94]
Friedman, S.J.; Skehan, P. Membrane-active drugs potentiate the killing of tumor cells by D-glucosamine. Proc. Natl. Acad. Sci. USA, 1980, 77(2), 1172-1176.
[http://dx.doi.org/10.1073/pnas.77.2.1172] [PMID: 6928667]
[95]
Oh, H-J.; Lee, J.S.; Song, D-K.; Shin, D-H.; Jang, B-C.; Suh, S-I.; Park, J-W.; Suh, M-H.; Baek, W-K. D-glucosamine inhibits proliferation of human cancer cells through inhibition of p70S6K. Biochem. Biophys. Res. Commun., 2007, 360(4), 840-845.
[http://dx.doi.org/10.1016/j.bbrc.2007.06.137] [PMID: 17624310]
[96]
Radimerski, T.; Montagne, J.; Rintelen, F.; Stocker, H.; van der Kaay, J.; Downes, C.P.; Hafen, E.; Thomas, G. dS6K-regulated cell growth is dPKB/dPI(3)K-independent, but requires dPDK1. Nat. Cell Biol., 2002, 4(3), 251-255.
[http://dx.doi.org/10.1038/ncb763] [PMID: 11862217]
[97]
Hornstein, E.; Tang, H.; Meyuhas, O. Mitogenic and nutritional signals are transduced into translational efficiency of TOP mRNAs. Cold Spring Harb. Symp. Quant. Biol., 2001, 66, 477-484.
[http://dx.doi.org/10.1101/sqb.2001.66.477] [PMID: 12762050]

Rights & Permissions Print Cite
Article Metrics
60
5
World Chagas Disease
© 2024 Bentham Science Publishers | Privacy Policy