Oak Brook, IL – The September edition of SLAS Discovery is a Special Collection featuring the cover article, "Applications of Biophysics in Early Drug Discovery" by Geoffrey A. Holdgate (AstraZeneca, Macclesfield, UK) and Christian Bergsdorf, Ph.D. (Novartis Institutes for Biomedical Research, Basel, Switzerland).
This special collection seeks to illustrate the existing and developing use of biophysical methods in the identification and characterization of molecules in early drug discovery. Many of these methods can be applied to understand the binding interactions of target proteins with small molecules as well as peptides, proteins, antibodies, sugars, and nucleic acids. This issue highlights the adaptation of existing and developing technologies that have successfully identified or characterized hits including graphene bioelectronic sensing technology, the application of thermal shift assays to screen compounds, fluorescence-based methods and light utilization.
Mass spectrometry (MS) facilitates fast target enablement in drug discovery via label-free quantification of relevant analytes and until recently did not meet the time efficiency standards of established optical methods. In the article "Acoustic Ejection Mass Spectrometry: A Fully Automatable Technology for High-Throughput Screening in Drug Discovery" by Roman P. Simon, et al., the authors describe the establishment of fully automated ADE-OPI-MS, enabled by the recently commercialized Echo-MS (Sciex) device as an in-line readout strategy for HTS. In the context of the model target cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS), the authors present the identification and optimization of critical ADE-OPI-MS method parameters to enable sub-second assessment of enzymatic activity directly from incubation mixtures in 1536-well format. The article describes the integration of this innovative readout technology into a fully automated assay platform to enable the unattended assessment of small molecule-mediated enzyme inhibition at HTS-capable throughput.
This issue of SLAS Discovery also includes three articles of original research:
- A High-Content Screening Assay for Small Molecules That Stabilize Mutant Triose Phosphate Isomerase (TPI) as Treatments for TPI Deficiency
- Establishing and Validating Cellular Functional Target Engagement Assay for Selective IRAK4 Inhibitor Discovery
- Functional and Pharmacological Comparison of Human and Mouse Na+/Taurocholate Cotransporting Polypeptide (NTCP)
Other articles in the Special Collection include:
- Discovery of the SMYD3 Inhibitor BAY-6035 Using Thermal Shift Assay (TSA)-Based High-Throughput Screening
- High-Throughput Affinity Selection Mass Spectrometry Using SAMDI-MS to Identify Small-Molecule Binders of the Human Rhinovirus 3C Protease
- Luminescence Energy Transfer-Based Screening and Target Engagement Approaches for Chemical Biology and Drug Discovery
- waveRAPID—A Robust Assay for High-Throughput Kinetic Screens with the Creoptix WAVEsystem
- Bioelectronic Measurement of Target Engagement to a Membrane-Bound Transporter
- Fast Mek1 Hit Identification with TRIC Technology Correlates Well with Other Biophysical Methods
- NMR Reporter Assays for the Quantification of Weak-Affinity Receptor–Ligand Interactions
- Technical Brief: Maintaining a High-Quality Screening Collection: The GSK Experience
Access to September's SLAS Discovery issue is available at https://journals.sagepub.com/toc/jbxb/current
