Pilot Screening of TREM1 Inhibitors in Cell-Based Reporter Assays Reflecting TREM1/DAP12 Receptor Assembly and Functionality.

ABSTRACT: Proinflammatory TREM1 receptors expressed on myeloid-derived cells have recently been recognized as a new oncogenic target in cancer, including gliomas. They are established chemotherapeutic targets in neurodegenerative Parkinson's and Alzheimer's diseases, and they also contribute to stroke and sepsis severities. TREM1 activation requires the TREM1/DAP12 interaction for receptor clustering and signal transduction coordinated by TREM1 ligands. Here, we established the quantitative cell-based high-throughput split luciferase assays of DAP12 dimerization, TREM1 dimerization, and TREM1/DAP12 interaction that allow screening of the inhibitory compounds with quantitative dose-responses, IC₅₀ values, and specificity evaluation. The assays are based on the reconstitution of firefly luc

SUBMITTER: Filippova N 

PROVIDER: S-EPMC12927207 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature