Newswise — Oak Brook, IL – Volume 43 of SLAS Discovery includes one review, seven original research articles and two entries from the Special Issue, High-Content Imaging and Informatics: 4th Joint Special Issue with the Society for Biomolecular Imaging & Informatics.
Review
Original Research
- A Hybrid Experimental and in silico Platform for ITPK1 Chemical Probe Discovery
Researchers combined a miniaturized 1,536-well high-throughput screen of approximately 19,000 compounds with machine learning and pharmacophore modeling to virtually screen an additional 120,000 compounds, identifying two novel ITPK1 inhibitor candidates with the help of a co-crystal structure and a novel target engagement assay. This integrated experimental and computational workflow—incorporating selectivity screening against the closely related PPIP5K2—offers an efficient, scalable strategy for drug discovery targeting inositol phosphate pathway-linked diseases.
- Three High Throughput Compatible Cell-Based Assays for Identifying Small Molecule JAG1 Upregulators for Alagille Syndrome The authors developed and benchmarked three high-throughput cell-based assays, RNA FISH, immunofluorescence and a HiBiT luminescence assay, to detect small-molecule upregulators of JAG1, the gene most frequently mutated in Alagille syndrome. All three assays identified overlapping active compounds, with the homogeneous HiBiT assay showing the most favorable screening statistics, providing a flexible platform for drug discovery targeting haploinsufficiency diseases.
- A High Throughput Screening Platform for Label-Free Identification and Characterization of GPCR Ligands Using Impedance-Based Real-Time Cellular Analysis
Researchers integrated the xCELLigence RTCA HT impedance-based biosensor system into a fully automated high-throughput screening platform, enabling label-free, kinetic monitoring of integrated GPCR cellular responses for large-scale agonist discovery. A proof-of-concept pilot HTS campaign demonstrated that real-time cell analysis is compatible with robotic screening workflows, highlighting its potential for identifying ligands for understudied and orphan GPCRs. - AI-Driven Identification of Zika Virus Inhibitors
Researchers combined a miniaturized 1,536-well Zika virus cytopathic effect assay with an ultra-high-throughput imager and two AI platforms—AVIA, which uses deep convolutional neural networks, and AutoHCS, which performs segmentation-free phenotypic profiling—to screen 1,280 unique compounds. AVIA distinguished infected from uninfected cells as early as 40 hours post-infection, and the combined AI approach identified 12 of 20 known hits while flagging false positives without additional counter-screens, demonstrating a cost- and time-effective route to antiviral discovery. - Forecasting a Clear Vision: How QSAR Modeling Catalyzes Small Molecule Discovery in the Field of Corneal Endothelial Regeneration
Researchers developed a weighted voting-based QSAR model to virtually screen a 460,160-compound library for small molecules that promote corneal endothelial regeneration, then validated the top four predicted compounds in vitro. All enhanced cell proliferation at nanomolar concentrations comparable to the ROCK inhibitor Y-27,632. This in silico-to-in vitro pipeline demonstrates a promising pharmacological alternative to donor tissue transplantation for corneal endothelial dysfunction, while providing new data to refine the predictive model. - Acoustic Ejection Native Mass Spectrometry for High-Throughput Protein-Ligand Screening
Researchers demonstrate that acoustic ejection mass spectrometry (AEMS) coupled to a high-resolution QTOF instrument enables high-throughput native mass spectrometry screening, using SARS-CoV-2 main protease (Mpro) as a model to simultaneously detect ligand binding, stoichiometry, and changes in oligomeric state. The authors analyzed a 1,536-well screening plate in about one hour, at 2.5 seconds per well, with excellent reproducibility, establishing acoustic ejection nMS as a practical platform for direct, information-rich screening of compound libraries. - Development of Diversified HTS Cell-Based Assays for Solute Carrier Drug Discovery
As part of the RESOLUTE consortium, researchers developed and miniaturized cell-based functional assays for five underexplored solute carrier (SLC) transporters—MFSD2A, MFSD2B, CRTR, NHA2, and NKCC1—implicated in various diseases but still lacking specific drugs. These HTS-compatible assays provide a valuable platform for rapidly and efficiently screening compound libraries to identify novel therapeutic modulators targeting this under-investigated class of membrane proteins.
Special Issue
Access to this volume of SLAS Discovery is available at https://www.slas-discovery.org/issue/S2472-5552(26)X2004-4
All active SLAS Discovery and SLAS Technology calls for papers are available at: https://www.slas.org/publications/call-for-papers/
*****
SLAS Discovery reports how scientists develop and use novel technologies and/or approaches to provide and characterize computational, chemical and biological tools to understand and treat human disease. The journal focuses on drug discovery sciences with a strong record of scientific rigor and impact, reporting on research that:
- Enables and improves target validation
- Shares and/or compare novel methods for medium- or high-throughput screening
- Evaluates current drug discovery technologies
- Provides novel research tools
- Incorporates research approaches that enhance depth of knowledge and drug discovery success
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, 2025 Impact Factor 3.3. Editor-in-Chief Robert M. Campbell, PhD, Grove Biopharma, Inc., Chicago, IL (USA)
###