× Medicines Discovery Catapult

The February special issue of SLAS Discovery, ‘Advances in Cellular Target Engagement and Target Deconvolution,’ features 11 articles focused on multiple aspects and technologies of cellular target engagement.

Special issue editors Martin Main, Ph.D., Head of Molecular Technologies, Medicines Discovery Catapult and Andrew Zhang, Ph.D., (AstraZeneca, USA) selected articles that span a variety of relevant topics, from the direct measurement of compound-target interaction using BRET technologies to the measurement of compound-induced changes in protein stability and localisation.


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The issue also features an article titled ‘The Opportunities and Use of Imaging to Ensure Target Engagement’ authored by Dr Juliana Maynard and Dr Philippa Hart, Lead Scientists at Medicines Discovery Catapult.

Proof of target engagement is a crucial element of drug discovery. While biochemical analysis of drug-target engagement is routinely deployed in projects, the ability to directly measure target engagement in cells and tissues, providing the critical link between drug-target binding and phenotype, is still in its relative infancy. As highlighted in this issue of SLAS Discovery, methods are emerging that allow for measuring cellular target engagement in a high-throughput and miniaturized manner, amenable for application in drug discovery projects. When applied in combination, these methods can build a strong platform of evidence linking compound to target to biological response, thereby impacting project attrition and medicine discovery success.

February’s SLAS Discovery includes the following reviews and perspectives:

  • High-Throughput Implementation of the NanoBRET® Target Engagement Intracellular Kinase Assay to Reveal Differential Compound Engagement by SIK2/3 Isoforms
  • A High-Throughput BRET Cellular Target Engagement Assay Links Biochemical-to-Cellular Activity for Bruton’s Tyrosine Kinase
  • Cellular Target Engagement Approaches to Monitor Epigenetic Reader Domain Interactions
  • NanoBiT Complementation to Monitor Agonist-Induced Adenosine A1 Receptor Internalization
  • Medium-Throughput Detection of Hsp90/Cdc37 Protein–Protein Interaction Inhibitors Using a Split Renilla Luciferase-Based Assay
  • Perspective on CETSA Literature – Towards More Quantitative Data Interpretation
  • Drug Target Engagement Using Coupled Cellular Thermal Shift AssayAcoustic Reverse Phase Protein Array
  • High-Throughput Cellular Thermal Shift Assays in Research and Drug Discovery
  • Over-Expression of Comprehensive Libraries of Human Proteins in a Cellular System Provides a Biologically Relevant Platform for Target Deconvolution
  • Bioorthogonal Reporters for Detecting and Profiling Protein Acetylation and Acylation
  • The Opportunities and Use of Imaging to Measure Target Engagement

Access to this special issue of SLAS Discovery is available here.

More information on MDC’s Pre-clinical Imaging expertise is available here.

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