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Updated: Jul 12, 2025
Author Spotlight: Balancing Speed, Cost, and Accuracy in Neutrophil Function Assessment with NeutroFun Screen Protocol
Published on: February 9, 2024
The Neutrophil Dynamic Mass Redistribution Assay as a Medium throughput Primary Cell Screening Assay
Lisa A Stott1, Armand Drieu la Rochelle2, Susan Brown2
1Sosei Heptares, Steinmetz Building, Granta Park, Cambridge, United Kingdom (L.A.S., A.D.R., S.B., G.O., S.P., K.A.B., M.B.); and Independent Consultant (C.J.H.) lisa.stott@soseiheptares.com.
A new dynamic mass redistribution (DMR) assay in primary human neutrophils offers a more physiologically relevant, medium-throughput screening method for drug discovery targeting CXC chemokine receptors (CXCR1/2). This assay improves compound progression confidence for inflammatory diseases and cancer.
Area of Science:
- Pharmacology
- Cell Biology
- Drug Discovery
Background:
- G protein-coupled receptor (GPCR) drug discovery typically progresses from recombinant to primary cell assays.
- CXC chemokine receptors (CXCR1/2) are implicated in inflammatory disorders and cancer.
- Existing assays in primary cells have limitations in throughput and reproducibility.
Purpose of the Study:
- To develop a medium-throughput dynamic mass redistribution (DMR) assay using primary human neutrophils.
- To assess the utility of this assay for screening compounds targeting CXCR1 and CXCR2.
- To evaluate the assay's physiological relevance and predictive power for drug discovery.
Main Methods:
- Established a dynamic mass redistribution (DMR) assay in primary human neutrophils.
- Utilized various chemokine ligands and CXCR1/2 antagonists (small and large molecules).
- Compared pharmacological profiles with recombinant assays and validated ex vivo assays (chemotaxis, CD11b upregulation).
Main Results:
- The neutrophil DMR assay demonstrated distinct pharmacological profiles compared to recombinant assays.
- Results from the DMR assay predicted activity in neutrophil chemotaxis and CD11b upregulation assays.
- The assay showed high reproducibility and robustness, with reduced donor variability.
Conclusions:
- The primary human neutrophil DMR assay provides a more physiologically relevant and higher-throughput screening platform.
- This assay enables earlier and more confident progression of drug candidates targeting CXCR1/2.
- It addresses the challenge of receptor redundancy and coexpression in chemokine receptor drug discovery.
