Oak Brook, IL – Volume 38 of SLAS Discovery includes one review, three original research articles, and the editorial of the recently published Special Issue, Protocols in 3D Biology: Technologies and Methodologies Reshaping 3D Cell Culture.

Review

From Large to Small Cytokine Receptor Antagonists

This review traces the evolution from biological drugs to small molecule cytokine antagonists, drawing on lessons from TNFα and IL-17 as key case studies. It looks ahead to emerging modalities, including extracellular degraders and oral peptides, that could unlock small molecule treatments for additional clinically validated cytokine targets, such as TSLP and TL1A.

Original Research An ELISA for Discovering Protein-Protein Interaction Inhibitors: Blocking Lysinoalanine Crosslinking Between Subunits of the Spirochete Flagellar Hook as a Test Case

This study introduces a versatile enzyme-linked immunosorbent assay (ELISA) platform for high-throughput screening of small molecule protein-protein interaction inhibitors. Screening ~700 compounds confirmed the action of a known inhibitor and uncovered two new candidates, honokiol and zafirlukast, demonstrating the assay’s broad utility for drug discovery.

Streamlining Cellular Thermal Shift Assay for Ultra-High Throughput Screening

This article presents two key cellular thermal shift assay innovations: an isothermal 1536-well uHTS platform with controlled thermal ramp-up and luminescence detection, and a Gradient Peltier Device enabling full melt curve analysis in a single plate. Together, these innovations overcome longstanding limitations in throughput and data quality. Both methods showed strong correlation with a fluorescence polarization assay using the androgen receptor as a benchmark, validating their potential for identifying true drug-target binders at scale.

MICRO-TAG Enzyme Complementation Enables Quantification of Cellular Drug-Target Engagement in Temperature Series

MICRO-TAG is a fluorescence-based split-RNase S complementation method that quantifies drug-target engagement directly in cells across programmable temperature series, mirroring conventional thermal shift assays rather than relying on a single melting point. Demonstrated across MAPK1, KRAS, and UBE2N targets, the approach offers a sensitive, scalable alternative to acellular biophysical methods for early-stage drug discovery.

Special Issue

All active SLAS Discovery and SLAS Technology call for papers are available at: https://www.slas.org/publications/call-for-papers/

Access to this volume of SLAS Discovery is available at https://www.slas-discovery.org/issue/S2472-5552(25)X0009-5

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