Identification and Characterization of Small Molecule Inhibitors of a Class I Histone Deacetylase from Plasmodium falciparum

[Image: see text] A library of approximately 2000 small molecules biased toward inhibition of histone deacetylases was assayed for antimalarial activity in a high-throughput P. falciparum viability assay. Active compounds were cross-analyzed for induction of histone hyperacetylation in a human myelo...

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Autores principales: Patel, Vishal, Mazitschek, Ralph, Coleman, Bradley, Nguyen, Cokey, Urgaonkar, Sameer, Cortese, Joseph, Barker, Robert H., Greenberg, Edward, Tang, Weiping, Bradner, James E., Schreiber, Stuart L., Duraisingh, Manoj T., Wirth, Dyann F., Clardy, Jon
Formato: Texto
Lenguaje:English
Publicado: American Chemical Society 2009
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669731/
https://www.ncbi.nlm.nih.gov/pubmed/19317450
http://dx.doi.org/10.1021/jm801654y
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author Patel, Vishal
Mazitschek, Ralph
Coleman, Bradley
Nguyen, Cokey
Urgaonkar, Sameer
Cortese, Joseph
Barker, Robert H.
Greenberg, Edward
Tang, Weiping
Bradner, James E.
Schreiber, Stuart L.
Duraisingh, Manoj T.
Wirth, Dyann F.
Clardy, Jon
author_facet Patel, Vishal
Mazitschek, Ralph
Coleman, Bradley
Nguyen, Cokey
Urgaonkar, Sameer
Cortese, Joseph
Barker, Robert H.
Greenberg, Edward
Tang, Weiping
Bradner, James E.
Schreiber, Stuart L.
Duraisingh, Manoj T.
Wirth, Dyann F.
Clardy, Jon
author_sort Patel, Vishal
collection PubMed
description [Image: see text] A library of approximately 2000 small molecules biased toward inhibition of histone deacetylases was assayed for antimalarial activity in a high-throughput P. falciparum viability assay. Active compounds were cross-analyzed for induction of histone hyperacetylation in a human myeloma cell line to identify HDAC inhibitors with selectivity for P. falciparum over the human host. To verify on-target selectivity, pfHDAC-1 was expressed and purified and a biochemical assay for pfHDAC-1 activity was established.
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spelling pubmed-26697312009-04-16 Identification and Characterization of Small Molecule Inhibitors of a Class I Histone Deacetylase from Plasmodium falciparum Patel, Vishal Mazitschek, Ralph Coleman, Bradley Nguyen, Cokey Urgaonkar, Sameer Cortese, Joseph Barker, Robert H. Greenberg, Edward Tang, Weiping Bradner, James E. Schreiber, Stuart L. Duraisingh, Manoj T. Wirth, Dyann F. Clardy, Jon J Med Chem [Image: see text] A library of approximately 2000 small molecules biased toward inhibition of histone deacetylases was assayed for antimalarial activity in a high-throughput P. falciparum viability assay. Active compounds were cross-analyzed for induction of histone hyperacetylation in a human myeloma cell line to identify HDAC inhibitors with selectivity for P. falciparum over the human host. To verify on-target selectivity, pfHDAC-1 was expressed and purified and a biochemical assay for pfHDAC-1 activity was established. American Chemical Society 2009-03-24 2009-04-23 /pmc/articles/PMC2669731/ /pubmed/19317450 http://dx.doi.org/10.1021/jm801654y Text en Copyright © 2009 American Chemical Society http://pubs.acs.org This is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org. 40.75
spellingShingle Patel, Vishal
Mazitschek, Ralph
Coleman, Bradley
Nguyen, Cokey
Urgaonkar, Sameer
Cortese, Joseph
Barker, Robert H.
Greenberg, Edward
Tang, Weiping
Bradner, James E.
Schreiber, Stuart L.
Duraisingh, Manoj T.
Wirth, Dyann F.
Clardy, Jon
Identification and Characterization of Small Molecule Inhibitors of a Class I Histone Deacetylase from Plasmodium falciparum
title Identification and Characterization of Small Molecule Inhibitors of a Class I Histone Deacetylase from Plasmodium falciparum
title_full Identification and Characterization of Small Molecule Inhibitors of a Class I Histone Deacetylase from Plasmodium falciparum
title_fullStr Identification and Characterization of Small Molecule Inhibitors of a Class I Histone Deacetylase from Plasmodium falciparum
title_full_unstemmed Identification and Characterization of Small Molecule Inhibitors of a Class I Histone Deacetylase from Plasmodium falciparum
title_short Identification and Characterization of Small Molecule Inhibitors of a Class I Histone Deacetylase from Plasmodium falciparum
title_sort identification and characterization of small molecule inhibitors of a class i histone deacetylase from plasmodium falciparum
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669731/
https://www.ncbi.nlm.nih.gov/pubmed/19317450
http://dx.doi.org/10.1021/jm801654y
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