A Definitive Synthesis of D‐myo‐Inositol 1,4,5,6‐Tetrakisphosphate and Its Enantiomer D‐myo‐Inositol 3,4,5,6‐Tetrakisphosphate from a Novel Butane‐2,3‐diacetal‐Protected Inositol.

Mills, Stephen; Riley, Andrew M.; Liu, Changsheng; Mahon, Mary F.; Potter, Barry V. L.

doi:10.1002/chin.200413165

Cited by 1 publication

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“…Ins(1,4,5,6)P 4 (25) and Ins(1,3,4,5,6)P 5 (24) were synthesized as previously reported. Each compound was purified to homogeneity by ion-exchange chromatography on Q-Sepharose Fast Flow resin and used as the triethylammonium salt, which was fully characterized by 31 P and 1 H spectroscopy, and accurately quantified by total phosphate assay.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of the Phosphatidylinositol 3-Kinase/Akt Pathway by Inositol Pentakisphosphate Results in Antiangiogenic and Antitumor Effects

Maffucci

Piccolo²,

Cumashi³

et al. 2005

Cancer Research

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The purpose of this study was to investigate the antiangiogenic and in vivo properties of the recently identified phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor Inositol(1,3,4,5,6) pentakisphosphate [Ins(1,3,4,5,6)P 5 ]. Because activation of the PI3K/Akt pathway is a crucial step in some of the events leading to angiogenesis, the effect of Ins(1,3,4,5,6)P 5 on basic fibroblast growth factor (FGF-2)-induced Akt phosphorylation, cell survival, motility, and tubulogenesis in vitro was tested in human umbilical vein endothelial cells (HUVEC). The effect of Ins(1,3,4,5,6)P 5 on FGF-2-induced angiogenesis in vivo was evaluated using s.c. implanted Matrigel in mice. In addition, the effect of Ins(1,3,4,5,6)P 5 on growth of ovarian carcinoma SKOV-3 xenograft was tested. Here, we show that FGF-2 induces Akt phosphorylation in HUVEC resulting in antiapoptotic effect in serum-deprived cells and increase in cellular motility. Ins(1,3,4,5,6)P 5 blocks FGF-2-mediated Akt phosphorylation and inhibits both survival and migration in HUVEC. Moreover, Ins(1,3,4,5,6)P 5 inhibits the FGF-2-mediated capillary tube formation of HUVEC plated on Matrigel and the FGF-2-induced angiogenic reaction in BALB/c mice. Finally, Ins(1,3,4,5,6)P 5 blocks the s.c. growth of SKOV-3 xenografted in nude mice to the same extent than cisplatin and it completely inhibits Akt phosphorylation in vivo. These data definitively identify the Akt inhibitor Ins(1,3,4,5,6)P 5 as a specific antiangiogenic and antitumor factor. Inappropriate activation of the PI3K/Akt pathway has been linked to the development of several diseases, including cancer, making this pathway an attractive target for therapeutic strategies. In this respect, Ins(1,3,4,5,6)P 5 , a water-soluble, natural compound with specific proapoptotic and antiangiogenic properties, might result in successful anticancer therapeutic strategies. (Cancer Res 2005; 65(18): 8339-49)

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Section: Methodsmentioning

confidence: 99%

Inhibition of the Phosphatidylinositol 3-Kinase/Akt Pathway by Inositol Pentakisphosphate Results in Antiangiogenic and Antitumor Effects

Maffucci

Piccolo²,

Cumashi³

et al. 2005

Cancer Research

Self Cite

120

133

View full text Add to dashboard Cite

show abstract

A Definitive Synthesis of D‐myo‐Inositol 1,4,5,6‐Tetrakisphosphate and Its Enantiomer D‐myo‐Inositol 3,4,5,6‐Tetrakisphosphate from a Novel Butane‐2,3‐diacetal‐Protected Inositol.

Abstract: A Definitive Synthesis of D-myo-Inositol 1,4,5,6-Tetrakisphosphate and Its Enantiomer D-myo-Inositol 3,4,5,6-Tetrakisphosphate from a Novel Butane-2,3-diacetal-Protected Inositol. -(MILLS, S. J.; RILEY, A. M.; LIU, C.; MAHON, M. F.; POTTER*, B. V. L.; Chem. Eur.

Cited by 1 publication

References 1 publication

Inhibition of the Phosphatidylinositol 3-Kinase/Akt Pathway by Inositol Pentakisphosphate Results in Antiangiogenic and Antitumor Effects

Inhibition of the Phosphatidylinositol 3-Kinase/Akt Pathway by Inositol Pentakisphosphate Results in Antiangiogenic and Antitumor Effects

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