Assays and technologies for developing proteolysis targeting chimera degraders
- 20 May 2020
- journal article
- review article
- Published by Future Science Ltd in Future Medicinal Chemistry
- Vol. 12 (12), 1155-1179
- https://doi.org/10.4155/fmc-2020-0073
Abstract
Targeted protein degradation by small-molecule degraders represents an emerging mode of action in drug discovery. Proteolysis targeting chimeras (PROTACs) are small molecules that can recruit an E3 ligase and a protein of interest (POI) into proximity, leading to induced ubiquitination and degradation of the POI by the proteasome system. To date, the design and optimization of PROTACs remain empirical due to the complicated mechanism of induced protein degradation. Nevertheless, it is increasingly appreciated that profiling step-by-step along the ubiquitin-proteasome degradation pathway using biochemical and biophysical assays are essential in understanding the structure–activity relationship and facilitating the rational design of PROTACs. This review aims to summarize these assays and to discuss the potential of expanding the toolbox with other new techniques.Keywords
This publication has 130 references indexed in Scilit:
- A quantitative homogeneous assay for fragile X mental retardation 1 proteinJournal of Neurodevelopmental Disorders, 2013
- Engineered Luciferase Reporter from a Deep Sea Shrimp Utilizing a Novel Imidazopyrazinone SubstrateACS Chemical Biology, 2012
- Screening for Novel LRRK2 Inhibitors Using a High-Throughput TR-FRET Cellular Assay for LRRK2 Ser935 PhosphorylationPLOS ONE, 2012
- Targeting the von Hippel–Lindau E3 Ubiquitin Ligase Using Small Molecules To Disrupt the VHL/HIF-1α InteractionJournal of the American Chemical Society, 2012
- Time-resolved Fluorescence Resonance Energy Transfer (TR-FRET) to Analyze the Disruption of EGFR/HER2 DimersJournal of Biological Chemistry, 2011
- Analysis of protein-ligand interactions by fluorescence polarizationNature Protocols, 2011
- Development of a homogeneous immunoassay for the detection of angiotensin I in plasma using AlphaLISA acceptor beads technologyAnalytical Biochemistry, 2009
- Recent applications of surface plasmon resonance biosensors for analyzing residues and contaminants in foodMonatshefte für Chemie / Chemical Monthly, 2009
- Mass Spectrometry Based Targeted Protein Quantification: Methods and ApplicationsJournal of Proteome Research, 2008
- The Use of AlphaScreen Technology in HTS: Current StatusCurrent Chemical Genomics, 2008