Journal ArticleDOI
Amide analogues of trichostatin A as inhibitors of histone deacetylase and inducers of terminal cell differentiation.
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TLDR
This is the first report that shows the correlation between HD inhibitory activity and action on cancer cells on a larger series of similar compounds, and supports the use of in vitro systems as screening tools and provides structure-activity relationships that merit further investigation of this interesting target.Abstract:
Inhibitors of histone deacetylase (HD) bear great potential as new drugs due to their ability to modulate transcription and to induce apoptosis or differentiation in cancer cells. We have described previously analogues of the complex natural HD inhibitors trapoxin B and trichostatin A with activities in the submicromolar range. Here we report structure-activity relationship analyses of further analogues of trichostatin A with respect to in vitro inhibition of maize HD-2 and their ability to induce terminal cell differentiation in Friend leukemic cells. This is the first report that shows the correlation between HD inhibitory activity and action on cancer cells on a larger series of similar compounds. Only the compounds that inhibit HD induce differentiation and/or exert antiproliferative activities in cell culture. Our studies support the use of in vitro systems as screening tools and provide structure-activity relationships that merit further investigation of this interesting target.read more
Citations
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Impact of natural products on developing new anti-cancer agents
TL;DR: This work presents a meta-analysis of the “Metagenome” of Cyanophytes and Marine Microbes, which highlights the importance of knowing the carrier and removal status of canine coronavirus, as a source of infection for other animals.
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
Fusion proteins of the retinoic acid receptor-alpha recruit histone deacetylase in promyelocytic leukaemia.
Fausto Grignani,S De Matteis,Clara Nervi,Lucia Tomassoni,Vania Gelmetti,M Cioce,M Fanelli,M Ruthardt,F F Ferrara,I Zamir,C Seiser,M A Lazar,Saverio Minucci,Pier Giuseppe Pelicci +13 more
TL;DR: It is shown that both PML–RARα and PLZF–Rarα fusion proteins recruit the nuclear co-repressor (N-CoR)–histone deacetylase complex through the RARα CoR box, which determines the differential response of APLs to RA.
Journal ArticleDOI
A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases
Victoria M. Richon,Stéphane Emiliani,Eric Verdin,Yael Webb,Ronald Breslow,Richard A. Rifkind,Paul A. Marks +6 more
TL;DR: These studies show that the second-generation HPCs, unlike HMBA, are potent inhibitors of HDAC activity, and appear to induce differentiation by different pathways.
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
The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB–binding protein
Julian Borrow,Vincent P. Stanton,J. Michael Andresen,Reinhard Becher,Frederick G. Behm,Raju S.K. Chaganti,Curt I. Civin,Christine M. Disteche,Ian D. Dubé,Anna Marie Frischauf,Doug Horsman,Felix Mitelman,Stefano Volinia,Ann E. Watmore,David E. Housman +14 more
TL;DR: It is suggested that MOZ may represent a chromatin-associated acetyltransferase, and the possibility that a dominant MOZ–CBP fusion protein could mediate leukaemogenesis via aberrant chromatin acetylation is raised.
Journal ArticleDOI
Cellular Differentiation Regulated by Gibberellin in the Arabidopsis thaliana pickle Mutant
Joe Ogas,Jin-Chen Cheng,Jin-Chen Cheng,Z. Renee Sung,Z. Renee Sung,Chris Somerville,Chris Somerville +6 more
TL;DR: In a screen for mutants, Arabidopsis plants carrying a mutation designated pickle (pkl) were isolated in which the primary root meristem retained characteristics of embryonic tissue.