Oak Brook, IL - The April edition of SLAS Discovery is a special issue on advances in protein degradation curated by guest editors M. Paola Castaldi, Ph.D., and Stewart L. Fisher, Ph.D.
Targeted protein degradation has generated interest within the drug discovery arena due to the inhibition of one particular function of a protein not often delivering the successful results that comes from whole-protein depletion. The pharmacology of PROTACs present challenges, however, namely for the development of orally bioavailable drugs. In the article "Target Validation Using PROTACs: Applying the Four Pillars Framework" authors Rados?aw P. Nowak, Ph.D., and Lyn H. Jones, Ph.D., describe the application of a translational pharmacology framework (the four pillars) to expedite PROTAC development by informing pharmacokinetic-pharmacodynamic (PKPD) understanding and helping clarify structure-activity relationships. Nowak and Jones hope that the four pillars will serve as a useful guideline to those developing targeted protein degraders and help establish PROTAC molecules as target validation chemical probes.
The April issue of SLAS Discovery includes three articles of original research.
These include:
Exploring the Biology of Degraders -- Simultaneous Detection of Protein Target Engagement and Functional Readout for In-Depth Characterization of Targeted Protein Degraders
A Method for Determining the Kinetics of Small Molecule Induced Ubiquitination
CDK Family PROTAC Degradation Profiling Reveals Differential Family Member Responses and Cell-Cycle Dependent Degradation of CDK
Other articles include:
Target Validation Using PROTACs: Applying the Four Pillars Framework
E3 Ligase Ligands for PROTACs: How They Were Found and How to Discover New Ones
Delivering Best Practice PROTACs Projects -- Lessons from AZ Experience.
High-Throughput Assay Technologies for Accelerating the Discovery and Optimization of Targeted Protein Degradation Therapeutics
The Vital Role of Proteomics in Characterizing Novel Protein Degraders
Non PROTAC Small Molecule Degraders -- An Exciting Novel Modality?
Development of a Novel SNAP-Epitope Tag/Near Infrared Imaging Assay to Quantify G Protein-Coupled Receptor Degradation in Human Cells