SLAS Discovery’s August Special Collection “Approaches for Prioritizing High-Quality Chemical Matter in Chemical Probe and Drug Discovery” Now Available

 

Oak Brook, IL – The August edition of SLAS Discovery is a Special Collection featuring the cover article, “Approaches for Prioritizing High-Quality Chemical Matter in Chemical Probe and Drug Discovery” by Jayme L. Dahlin, M.D., Ph.D. (Brigham and Women’s Hospital, Boston, MA, USA).

In drug discovery, drug binding to the target is a critical measurement for optimizing new therapeutics and for testing their efficacy and safety. This measurement is based on classical pharmacological theory. When pharmacology theory was developed in the mid-20th Century, assay conditions were very different from today – moderately active natural products were tested at low target density on tissues in high volume organ baths. Today testing is done on highly potent compounds at high target density in low volume microtiter plates. These new conditions can invalidate two assumptions of classical pharmacology analysis still used to analyze the data today: low target density and rapid binding kinetics.

“The Problems of Applying Classical Pharmacology Analysis to 835 Modern In Vitro Drug Discovery Assays: Slow Binding Kinetics and High Target Concentration” by Sam R. J. Hoare, Ph.D., (Pharmechanics, LLC, Owego, NY, USA) describes what happens when these conditions are infringed in modern assays. Drug potency can be dramatically underestimated, affecting lead optimization and prediction of human dosing. HTS assays ideally suited to find initial leads often profoundly distort potency measurements of high affinity candidates. These problems are readily identifiable if investigators are aware of them. In the review, the assays and compound potency ranges susceptible to target density and equilibration artifacts are described. Methods and diagnostic observations to detect the artifacts are also described. The review enables scientists to evaluate, manage and minimize target density and equilibration artifacts to improve quantification of drug-target interaction and therefore maximize the chance of success in their drug discovery project.

 

The August issue of SLAS Discovery includes six articles of original research.

These include:

• In Vitro Ubiquitination Platform Identifies Methyl Ellipticiniums as Ubiquitin Ligase Inhibitors
• A Phenotypic Approach for the Identification of New Molecules for Targeted Protein Degradation Applications
• Discovery of Novel HCN4 Blockers with Unique Blocking Kinetics and Binding Properties
• Epithelial Barrier Integrity Profiling: Combined Approach Using Cellular Junctional Complex Imaging and Transepithelial Electrical Resistance
• Sensitivity of Oncogenic KRAS-Expressing Cells to CDK9 Inhibition
• Development of a High-Throughput, Compound-Multiplexed Fluorescence Polarization Assay to Identify ATG5–ATG16L1 Protein–Protein Interaction Inhibitors

 

Other articles include:

• Approaches for Prioritizing High-Quality Chemical Matter in Chemical Probe and Drug Discovery
• The Problems of Applying Classical Pharmacology Analysis to Modern In Vitro Drug Discovery Assays: Slow Binding Kinetics and High Target Concentration
• Brief Guide: Experimental Strategies for High-Quality Hit Selection from Small-Molecule Screening Campaigns
• The Use of Informer Sets in Screening: Perspectives on an Efficient Strategy to Identify New Probes
• The Communication of Hit Quality Using Natural History Visualizations (NHVs)

Access to August’s SLAS Discovery issue is available at https://journals.sagepub.com/toc/jbxb/current. For more information about SLAS and its journals, visit https://www.slas.org/publications/slas-discovery/ Access a “behind the scenes” look at the latest issue with SLAS Discovery Author Insights podcast. Tune in by visiting https://www.buzzsprout.com/1099559.

 

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SLAS (Society for Laboratory Automation and Screening) is an international professional society of academic, industry and government life sciences researchers and the developers and providers of laboratory automation technology. The SLAS mission is to bring together researchers in academia, industry and government to advance life sciences discovery and technology via education, knowledge exchange and global community building.

 

SLAS Discovery: Advancing the Science of Drug Discovery, 2019 Impact Factor 2.918. Editor-in-Chief Robert M. Campbell, Ph.D., Twentyeight-Seven Therapeutics, Boston, MA (USA).

 

SLAS Technology: Translating Life Sciences Innovation, 2019 Impact Factor 3.047. Editor-in-Chief Edward Kai-Hua Chow, Ph.D., National University of Singapore (Singapore).

 

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