High-Throughput Phenotypic Screen to Identify FoxP3 Regulators in Primary T Cells

T cells, using an automated liquid handling pipeline. Selected hit candidates from the screening were validated and assessed through functional analyses. From screening a library of approved drugs, we identified several candidates that regulate Treg functions through FoxP3. Seventeen chemical analogs of one hit compound were identified and characterized in cell-based assays, revealing structure-activity relationships and identifying compounds with more potent effects on the regulation of FoxP3 levels and Treg function. We conclude that this novel screening method could successfully identify FoxP3 regulators with an effect on Treg functions.