Journal ArticleDOI
Synthesis and Histone Deacetylase Inhibitory Activity of New Benzamide Derivatives
Tsuneji Suzuki,Tomoyuki Ando,Katsutoshi Tsuchiya,Nobuyuki Fukazawa,Akiko Saito,Yukiyasu Mariko,Takashi Yamashita,Osamu Nakanishi +7 more
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TLDR
In this paper, new synthesized benzamide derivatives were evaluated for their inhibitory activity against histone deacetylase, and the IC50 values of the active compounds were in the range of 2−50 μM.Abstract:
Newly synthesized benzamide derivatives were evaluated for their inhibitory activity against histone deacetylase. The structure of these derivatives was unrelated to the known inhibitors, and IC50 values of the active compounds were in the range of 2−50 μM. Structure−activity relationship on the benzanilide moiety showed that the 2‘-substituent, an amino or hydroxy group, was indispensable for inhibitory activity. Although the electronic influence of the substituent in the anilide moiety showed only a small effect on inhibitory activity, the steric factor in the anilide moiety, especially at positions 3‘and 4‘, played an important role in interaction with the enzyme. Among these benzamide derivatives, MS-275 (1), which showed significant antitumor activity in vivo, has been selected for further investigation.read more
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Journal ArticleDOI
Histone deacetylases and cancer: causes and therapies.
Paul A. Marks,Richard A. Rifkind,Victoria M. Richon,Ronald Breslow,Thomas E. Miller,William Kevin Kelly +5 more
TL;DR: Together, histone acetyltransferases and histone deacetylases determine the acetylation status of histones, and inhibitors of HDACs have been found to cause growth arrest, differentiation and/or apoptosis of many tumours cells by altering the transcription of a small number of genes.
Journal ArticleDOI
Histone deacetylase inhibitors.
TL;DR: Design of a second generation ofHDACs was based upon data affording potent HDACs such as LAQ824 and PDX101 currently under phase I clinical trials, and two of them, MS-275 and CI-994, have reached phase II and I clinical Trials, respectively.
PatentDOI
Histone deacetylase inhibitors
TL;DR: This review encompasses the medicinal chemistry and structureactivity relationships (SAR) underlying advances in HDAC class I/II inhibitor discovery, design, and optimization.
Journal ArticleDOI
Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention
Fumin Chang,Linda S. Steelman,John T. Lee,John G. Shelton,Patrick M. Navolanic,William L. Blalock,William L. Blalock,Richard A. Franklin,James A. McCubrey +8 more
TL;DR: The current understanding of the Ras/Raf/MEK/ERK signal transduction pathway and the downstream transcription factors is summarized and the prospects of targeting this pathway for therapeutic intervention in leukemia and other cancers will be evaluated.
Patent
Inhibitors of histone deacetylase
Oscar Moradei,Isabelle Paquin,Silvana Leit,Sylvie Frechette,Arkadii Vaisburg,Jeffrey M. Besterman,Pierre Tessier,Tammy C. Mallais +7 more
TL;DR: In this article, the authors provide compounds and methods for inhibiting histone deacetylase enzymatic activity and also provide compositions for treating cell proliferative diseases and conditions.
References
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Journal ArticleDOI
Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A.
TL;DR: Results clearly indicate that TSA is a potent and specific inhibitor of the histone deacetylase and that the in vivo effect of TSA on cell proliferation and differentiation can be attributed to the inhibition of the enzyme.
Journal ArticleDOI
Effects of sodium butyrate, a new pharmacological agent, on cells in culture
TL;DR: Sodium butyrate, at millimolar concentrations, when added to cell cultures produces many morphological and biochemical modifications in a reversible manner that concern regulatory mechanisms of gene expression and cell growth.
Journal ArticleDOI
A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors
Akiko Saito,Takashi Yamashita,Yukiyasu Mariko,Yasuhito Nosaka,Katsutoshi Tsuchiya,Tomoyuki Ando,Tsuneji Suzuki,Takashi Tsuruo,Osamu Nakanishi +8 more
TL;DR: Results suggest that MS-27-275 acts as an antitumor agent through HDA inhibition and may provide a novel chemotherapeutic strategy for cancers insensitive to traditional antitumors.
Journal ArticleDOI
Trapoxin, an antitumor cyclic tetrapeptide, is an irreversible inhibitor of mammalian histone deacetylase.
TL;DR: The results strongly suggest that the in vivo effects commonly induced by these agents can be attributed to histone hyperacetylation resulting from the inhibition of histone deacetylase.
Journal ArticleDOI
Histone acetylation: chromatin in action
TL;DR: Active roles in the transcription and assembly of chromatin have been discovered for histone acetyltransferases and deacetylases and their significance for the maintenance of cell differentiation is discussed.