Molecular glues to stabilise protein–protein interactions

Targeting protein–protein interactions (PPIs) has become a common approach to tackle various diseases whose pathobiology is driven by their mis-regulation in important signalling pathways. Modulating PPIs has tremendous untapped therapeutic potential and different approaches can be used to modulate...

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Bibliographic Details
Published in:Current opinion in chemical biology Vol. 69; p. 102169
Main Authors: Soini, Lorenzo, Leysen, Seppe, Davis, Jeremy, Ottmann, Christian
Format: Journal Article
Language:English
Published: Elsevier Ltd 01.08.2022
ISSN:1367-5931, 1879-0402, 1879-0402
Online Access:Get full text
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Summary:Targeting protein–protein interactions (PPIs) has become a common approach to tackle various diseases whose pathobiology is driven by their mis-regulation in important signalling pathways. Modulating PPIs has tremendous untapped therapeutic potential and different approaches can be used to modulate PPIs. Initially, therapeutic effects were mostly sought by inhibiting PPIs. However, by gaining insight in the mode of action of certain therapeutic compounds, it became clear that stabilising (i.e. enhancing) PPIs can also be useful. The latter strategy is recently gaining a lot of attention, as stabilising physiologic, or even inducing novel interactions of a target protein with E3 ubiquitin ligases forms the basis of the targeted protein degradation (TPD) approach. An emerging additional example for drug discovery based on PPI stabilisation are the 14-3-3 proteins, a family of regulatory proteins, which engages in many protein–protein interactions, some of which might become therapeutical targets.
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ISSN:1367-5931
1879-0402
1879-0402
DOI:10.1016/j.cbpa.2022.102169