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  Pyrido- and benzisothiazolones as inhibitors of histone acetyltransferases (HATs)

Furdas, S. D., Hoffmann, I., Robaa, D., Herquel, B., Malinka, W., Świątek, P., et al. (2014). Pyrido- and benzisothiazolones as inhibitors of histone acetyltransferases (HATs). Medicinal Chemistry Communications, 5, 1856-1862. doi:10.1039/C4MD00245H.

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Furdas et al. 2014.pdf (Publisher version), 298KB
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Furdas et al. 2014.pdf
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2014
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The Royal Society of Chemistry

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 Creators:
Furdas, S. D.1, Author
Hoffmann, I.1, Author
Robaa, D.1, Author
Herquel, Benjamin2, Author
Malinka, W.1, Author
Świątek, P.1, Author
Akhtar, Asifa2, Author              
Sippl, W.1, Author
Jung, M.1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243643              

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 Abstract: Histone acetyltransferases (HATs) are interesting targets for the treatment of cancer and HIV infections but reports on selective inhibitors are very limited. Here we report structure–activity studies of pyrido- and benzisothiazolones in the in vitro inhibition of histone acetyltransferases, namely PCAF, CBP, Gcn5 and p300 using a heterogeneous assay with antibody mediated quantitation of the acetylation of a peptidic substrate. Dependent on the chemical structure distinct subtype selectivity profiles can be obtained. While N-aryl derivatives usually are rather pan-HAT inhibitors, N-alkyl derivatives show mostly a preference for CBP/p300. Selected compounds were also shown to be inhibitors of MOF. The best inhibitors show submicromolar inhibition of CBP. Selected compounds affect growth of HL-60 leukemic cells and LNCaP prostate carcinoma cells with higher potency on the leukemic cells. Target engagement was shown with reduction of histone acetylation in LNCaP cells.

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Language(s): eng - English
 Dates: 2014-08-11
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1039/C4MD00245H
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Title: Medicinal Chemistry Communications
  Abbreviation : MedChemComm
Source Genre: Journal
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Publ. Info: (United Kingdom : Royal Society of Chemistry
Pages: - Volume / Issue: 5 Sequence Number: - Start / End Page: 1856 - 1862 Identifier: ISSN: 2040-2503
CoNE: https://pure.mpg.de/cone/journals/resource/2040-2503