Publication

Genie in a bottle: controlled release helps tame natural polypharmacology?

Yimon Aye, Xuyu Liu
2019
Reviews

Abstract

Ability to faithfully report drug-target interactions constitutes a major critical parameter in preclinical/clinical settings. Yet the assessment of target engagement remains challenging, particularly for promiscuous and/or polypharmacologic ligands. Drawing from our improved insights into native electrophile signaling and emerging technologies that profile and interrogate these non-enzyme-assisted signaling subsystems, we posit that ‘trained’ polypharmocologic covalent inhibitors can be designed. Accumulating evidence indicates that electrophile-modified states at fractional occupancy can alter cell fate. Thus, by understanding sensing preferences and ligandable regions favored by the natural electrophilic signals at individual protein–ligand resolution, we can better evaluate target engagement and develop a function-guided understanding of polypharmacology.

Official source

https://infoscience.epfl.ch/entities/publication/8309315d-499b-44a6-b360-941eb0560ddb

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Yimon Aye, Xuyu Liu
2019
Reviews

Abstract

Official source

https://infoscience.epfl.ch/entities/publication/8309315d-499b-44a6-b360-941eb0560ddb

About this result

Related concepts (16)

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In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate, the binding site, and residues that catalyse a reaction of that substrate, the catalytic site. Although the active site occupies only ~10–20% of the volume of an enzyme, it is the most important part as it directly catalyzes the chemical reaction.

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