The polypharmacology strategy of multi-targeting drugs acting on different biological pathways is capturing the researchers' attention, particularly in cancer. The simultaneous inhibition of two or more targets by drug combination or by a single 'hybrid molecule' can provide improved therapeutic efficacy when compared to the one-target inhibitors. In this regard, because of their multiple anticancer effects, histone deacetylase inhibitors have become a privileged tool for the development of hybrid drugs. The clinical trials of two multi-acting chimeras, HDAC/EGFR/HER2 and HDAC/PI3K inhibitors, encouraged the design of novel hybrids, such as compounds 22a (LSD1/HDAC) and 16a (CDK4/JAK1/HDAC), which showed superior anticancer effects than single-targeting agents or their combination both in cellular and mouse models.

Histone deacetylases as an epigenetic pillar for the development of hybrid inhibitors in cancer / Stazi, Giulia; Fioravanti, Rossella; Mai, Antonello; Mattevi, Andrea; Valente, Sergio. - In: CURRENT OPINION IN CHEMICAL BIOLOGY. - ISSN 1367-5931. - 50:(2019), pp. 89-100. [10.1016/j.cbpa.2019.03.002]

Histone deacetylases as an epigenetic pillar for the development of hybrid inhibitors in cancer

Giulia Stazi;Rossella Fioravanti;Antonello Mai
;
Sergio Valente
2019

Abstract

The polypharmacology strategy of multi-targeting drugs acting on different biological pathways is capturing the researchers' attention, particularly in cancer. The simultaneous inhibition of two or more targets by drug combination or by a single 'hybrid molecule' can provide improved therapeutic efficacy when compared to the one-target inhibitors. In this regard, because of their multiple anticancer effects, histone deacetylase inhibitors have become a privileged tool for the development of hybrid drugs. The clinical trials of two multi-acting chimeras, HDAC/EGFR/HER2 and HDAC/PI3K inhibitors, encouraged the design of novel hybrids, such as compounds 22a (LSD1/HDAC) and 16a (CDK4/JAK1/HDAC), which showed superior anticancer effects than single-targeting agents or their combination both in cellular and mouse models.
2019
epigenetic; hydroxamic acid-derivatives; dual inhibitors; in-vitro; biological evaluation; hdac inhibitors; pathway inhibition; rational design; combination; discovery; vorinostat
01 Pubblicazione su rivista::01g Articolo di rassegna (Review)
Histone deacetylases as an epigenetic pillar for the development of hybrid inhibitors in cancer / Stazi, Giulia; Fioravanti, Rossella; Mai, Antonello; Mattevi, Andrea; Valente, Sergio. - In: CURRENT OPINION IN CHEMICAL BIOLOGY. - ISSN 1367-5931. - 50:(2019), pp. 89-100. [10.1016/j.cbpa.2019.03.002]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1416968
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