Quinazolines as inhibitors of chromatin-associated proteins in histones View Full Text


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Article Info

DATE

2019-02-04

AUTHORS

Frida S. Herrera-Vázquez, Francisco Hernández-Luis, José L. Medina Franco

ABSTRACT

It is increasing the evidence that quinazolines are inhibitors of chromatin-associated proteins in histones. Quinazolines have a broad structural diversity among the structural classes that have been designed. Herein, we review the development of selective and potent quinazolines highlighting the current state of these molecules with an emphasis on the structural requirements for the interaction within the target. Chemical synthesis and results of the biological assays in vitro or in vivo of these compounds are also discussed. There is extensive evidence that support quinazoline derivatives as inhibitors of histone methyltransferase (G9a) and G9a-like protein (GLP). There is one quinazoline analogue that inhibits an extra-terminal bromodomain motif (BET) and that is on clinical trials as potential treatment for different chronic diseases. There is also clinical evidence that quinazolines act as dual inhibitors targeting histone deacetylases (HDACs) Zn2+-dependent and kinase receptors for the potential treatment of cancer. Additional proposals of quinazoline structures are being evaluated as inhibitors targeting two or more chromatin-associated proteins simultaneously. Therefore, further improvements in synthetic methods, computational studies, and additional biological assays in vitro and in vivo remain to be addressed. More... »

PAGES

395-416

References to SciGraph publications

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  • 2009-09-24. EVI-1 interacts with histone methyltransferases SUV39H1 and G9a for transcriptional repression and bone marrow immortalization in LEUKEMIA
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  • 2014-08-18. Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders in NATURE REVIEWS DRUG DISCOVERY
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  • 1999-09. Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors in NATURE
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  • 2006-09. Anticancer activities of histone deacetylase inhibitors in NATURE REVIEWS DRUG DISCOVERY
  • 2013-10-23. Chromatin proteins and modifications as drug targets in NATURE
  • 2011-07-10. A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells in NATURE CHEMICAL BIOLOGY
  • 2007-03-06. Cancer epigenomics: DNA methylomes and histone-modification maps in NATURE REVIEWS GENETICS
  • 2010-09-24. Selective inhibition of BET bromodomains in NATURE
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    http://scigraph.springernature.com/pub.10.1007/s00044-019-02300-0

    DOI

    http://dx.doi.org/10.1007/s00044-019-02300-0

    DIMENSIONS

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