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

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

  • Long MJ 47 Pudding Gate, Bishop Burton, Beverley East Riding of Yorkshire, HU17 8QH, UK.
  • Liu X École Polytechnique Fédérale de Lausanne, Institute of Chemical Sciences and Engineering, 1015, Lausanne, Switzerland.
  • Aye Y École Polytechnique Fédérale de Lausanne, Institute of Chemical Sciences and Engineering, 1015, Lausanne, Switzerland. Electronic address: yimon.aye@epfl.ch.
  • 2019-03-27
Published in:
  • Current opinion in chemical biology. - 2019
Biological Products
Delayed-Action Preparations
Humans
Ligands
Polypharmacology
Protein Binding
Signal Transduction
English 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.
Language
  • English
Open access status
green
Identifiers
Persistent URL
https://sonar.ch/global/documents/97020
Statistics
Document views: 47 File downloads: