Oak Brook, IL – Volume 40 of SLAS Discovery includes four original research articles covering innovative screening platforms and assay technologies that accelerate drug discovery across neurodegenerative disease, transporter biology and challenging protein-protein interactions.
Original Research
- High-Throughput Screening of ALS Patient iPSC-Derived Spinal Motor Neurons Identifies Novel Compounds that Increase Neurofilament Light Chain Expression
The authors engineer patient-derived induced pluripotent stem cells to generate spinal motor neurons, developing a high-throughput screening platform to screen over 6,000 compounds. l Novel candidates that increased neurofilament light chain expression in ALS (amyotrophic lateral sclerosis) models are identified and through subsequent investigations, the researchers identify a lead candidate that avoids TGF-β inhibition and demonstrates improved drug metabolism and pharmacokinetics. This approach yielded a promising new avenue for ALS therapy and highlights the utility of iPSC-derived neurons in disease modeling.
- A Versatile Acoustic Droplet Ejection Mass Spectrometry Platform Enables Drug Discovery for the Solute Carrier (SLC) Target Family
This study establishes a high-throughput assay platform using acoustic ejection mass spectrometry that can quantify a broad range of substrates transported by solute carrier (SLC) proteins, a major class of drug targets. The platform was successfully validated across multiple SLC sub-families and scaled for hit identification in a pilot screening campaign against SGLT2, positioning it as a versatile, universal tool for discovering and characterizing SLC modulators.
- Development of a Nanobit-Based High-Throughput Screening Assay for Discovery of NOS1-NOS1AP Interaction Inhibitors
Researchers develop and validate a nanobit-based luminescence complementation assay for high-throughput screening of inhibitors targeting the NOS1-NOS1AP protein-protein interaction—a pathway implicated in cardiovascular and neuropsychiatric disorders. By screening over 10,000 compounds, 19 validated hits are identified, including three with potent inhibitory activity, providing a reliable platform for discovering new therapeutics that disrupt this challenging target.
- Identification of a Small Molecule CAPON Binder Using Affinity Selection-Mass Spectrometry Screening
The authors identify the first small-molecule binder for CAPON (NOS1AP), an adaptor protein linked to Alzheimer's disease progression, using affinity selection–mass spectrometry to screen approximately 10,000 compounds. The lead compound, MA32, binds CAPON with a dissociation constant of 74 µM, revealing a druggable pocket on this previously unexplored target, providing a critical starting point for developing chemical probes and potential therapeutics.
Access to this volume of SLAS Discovery is available at https://www.slas-discovery.org/issue/S2472-5552(26)X2001-9
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