Synthesis of hybrid anticancer agents based on kinase and histone deacetylase inhibitors

Hiren Patel; Irina Chuckowree; Peter Coxhead; Matthew Guille; Minghua Wang; Alexandra Zuckermann; Robin S. B. Williams; Mariangela Librizzi; Ronald M. Paranal; James E. Bradner; John Spencer

doi:10.1039/C4MD00211C

Synthesis of hybrid anticancer agents based on kinase and histone deacetylase inhibitors

Hiren Patel, Irina Chuckowree, Peter Coxhead, Matthew Guille, Minghua Wang, Alexandra Zuckermann, Robin S. B. Williams, Mariangela Librizzi, Ronald M. Paranal, James E. Bradner, John Spencer

Research output: Contribution to journal › Article › peer-review

Abstract

Fragments based on the VEGFR2i Semaxanib (SU5416, (vascular endothelial growth factor receptor-2 inhibitor) and the HDACi (histone deacetylase inhibitor) SAHA (suberanilohydroxamic acid) have been merged to form a range of low molecular weight dual action hybrids. Vindication of this approach is provided by SAR, docking studies, in vitro cancer cell line and biochemical enzyme inhibition data as well as in vivo Xenopus data for the lead molecule (Z)-N1-(3-((1H-pyrrol-2-yl)methylene)-2-oxoindolin-5-yl)-N8-hydroxyoctanediamide 6.

Original language	English
Pages (from-to)	1829-1833
Journal	MedChemComm
Volume	5
Early online date	18 Jun 2014
DOIs	https://doi.org/10.1039/C4MD00211C
Publication status	Published - 1 Dec 2014

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title = "Synthesis of hybrid anticancer agents based on kinase and histone deacetylase inhibitors",

abstract = "Fragments based on the VEGFR2i Semaxanib (SU5416, (vascular endothelial growth factor receptor-2 inhibitor) and the HDACi (histone deacetylase inhibitor) SAHA (suberanilohydroxamic acid) have been merged to form a range of low molecular weight dual action hybrids. Vindication of this approach is provided by SAR, docking studies, in vitro cancer cell line and biochemical enzyme inhibition data as well as in vivo Xenopus data for the lead molecule (Z)-N1-(3-((1H-pyrrol-2-yl)methylene)-2-oxoindolin-5-yl)-N8-hydroxyoctanediamide 6.",

author = "Hiren Patel and Irina Chuckowree and Peter Coxhead and Matthew Guille and Minghua Wang and Alexandra Zuckermann and Williams, {Robin S. B.} and Mariangela Librizzi and Paranal, {Ronald M.} and Bradner, {James E.} and John Spencer",

note = "Can we validate without post-print as an early one.",

year = "2014",

month = dec,

day = "1",

doi = "10.1039/C4MD00211C",

language = "English",

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journal = "MedChemComm",

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T1 - Synthesis of hybrid anticancer agents based on kinase and histone deacetylase inhibitors

AU - Patel, Hiren

AU - Chuckowree, Irina

AU - Coxhead, Peter

AU - Guille, Matthew

AU - Wang, Minghua

AU - Zuckermann, Alexandra

AU - Williams, Robin S. B.

AU - Librizzi, Mariangela

AU - Paranal, Ronald M.

AU - Bradner, James E.

AU - Spencer, John

N1 - Can we validate without post-print as an early one.

PY - 2014/12/1

Y1 - 2014/12/1

N2 - Fragments based on the VEGFR2i Semaxanib (SU5416, (vascular endothelial growth factor receptor-2 inhibitor) and the HDACi (histone deacetylase inhibitor) SAHA (suberanilohydroxamic acid) have been merged to form a range of low molecular weight dual action hybrids. Vindication of this approach is provided by SAR, docking studies, in vitro cancer cell line and biochemical enzyme inhibition data as well as in vivo Xenopus data for the lead molecule (Z)-N1-(3-((1H-pyrrol-2-yl)methylene)-2-oxoindolin-5-yl)-N8-hydroxyoctanediamide 6.

AB - Fragments based on the VEGFR2i Semaxanib (SU5416, (vascular endothelial growth factor receptor-2 inhibitor) and the HDACi (histone deacetylase inhibitor) SAHA (suberanilohydroxamic acid) have been merged to form a range of low molecular weight dual action hybrids. Vindication of this approach is provided by SAR, docking studies, in vitro cancer cell line and biochemical enzyme inhibition data as well as in vivo Xenopus data for the lead molecule (Z)-N1-(3-((1H-pyrrol-2-yl)methylene)-2-oxoindolin-5-yl)-N8-hydroxyoctanediamide 6.

U2 - 10.1039/C4MD00211C

DO - 10.1039/C4MD00211C

M3 - Article

SN - 2040-2503

VL - 5

SP - 1829

EP - 1833

JO - MedChemComm

JF - MedChemComm

ER -

Synthesis of hybrid anticancer agents based on kinase and histone deacetylase inhibitors

Abstract

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