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Design, Synthesis and Inhibitory Activity of Photoswitchable RET Kinase Inhibitors.

Rubén Ferreira (Institutionen för kemi och kemiteknik) ; Jesper Nilsson (Institutionen för kemi och kemiteknik, Fysikalisk kemi) ; Carlos Solano ; Joakim Andréasson (Institutionen för kemi och kemiteknik, Fysikalisk kemi) ; Morten Grøtli
Scientific reports (2045-2322). Vol. 5 (2015), p. artikel nr 9769.
[Artikel, refereegranskad vetenskaplig]

REarranged during Transfection (RET) is a transmembrane receptor tyrosine kinase required for normal development and maintenance of neurons of the central and peripheral nervous systems. Deregulation of RET and hyperactivity of the RET kinase is intimately connected to several types of human cancers, most notably thyroid cancers, making it an attractive therapeutic target for small-molecule kinase inhibitors. Novel approaches, allowing external control of the activity of RET, would be key additions to the signal transduction toolbox. In this work, photoswitchable RET kinase inhibitors based on azo-functionalized pyrazolopyrimidines were developed, enabling photonic control of RET activity. The most promising compound displays excellent switching properties and stability with good inhibitory effect towards RET in cell-free as well as live-cell assays and a significant difference in inhibitory activity between its two photoisomeric forms. As the first reported photoswitchable small-molecule kinase inhibitor, we consider the herein presented effector to be a significant step forward in the development of tools for kinase signal transduction studies with spatiotemporal control over inhibitor concentration in situ.



Denna post skapades 2015-05-28. Senast ändrad 2016-10-24.
CPL Pubid: 217693

 

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Institutioner (Chalmers)

Institutionen för kemi och kemiteknik
Institutionen för kemi och kemiteknik, Fysikalisk kemi
Institutionen för kemi och molekylärbiologi (GU)

Ämnesområden

Kemi

Chalmers infrastruktur

 


Projekt

Denna publikation är ett resultat av följande projekt:


Photochromic systems for solid state molecular electronic devices and light-activated cancer drugs (PHOTOCHROMES) (EC/FP7/203952)