Introduction/Rationale: BKT300 is a novel small molecule with potent anti inflammatory and immune modulating activity. BKT300 is an inhibitor of Protein Regulator of Cytokinesis 1 (PRC1), a cytoskeleton associated protein mainly studied in cancer. Pan cancer analyses associate high PRC1 expression with immunosuppressive environments enriched in regulatory T cells, PMN MDSCs and Th2 cells, with reduced CD8 T cells and B cells and increased immune checkpoint expression. However, the role of PRC1 in non malignant inflammation remains poorly defined. We therefore examined whether BKT300 modulates immune cell migration and inflammatory responses.
Methods: Immune cell migration was assessed in vitro using chemotaxis assays of normal human T cells toward SDF 1 and monocytes toward MCP 1. Cytoskeletal organization was evaluated by analysis of actin filament formation and microtubule assembly. In vivo activity was examined in murine delayed type hypersensitivity (DTH) and MC903 induced atopic dermatitis models following topical, subcutaneous or oral administration.
Results: BKT300 potently inhibited migration of human T cells and monocytes at picomolar concentrations and disrupted actin filament formation and microtubule assembly, key processes for immune cell motility. In vivo, BKT300 significantly reduced inflammation in the DTH model, decreasing ear swelling, inflammatory infiltration and tissue damage after topical or subcutaneous administration, with greater efficacy than dexamethasone. In the MC903 atopic dermatitis model, BKT300 consistently reduced ear thickness and epidermal hyperplasia following topical, subcutaneous or oral administration. BKT300 was more effective than Clobetasol, remained active at low doses and showed no adverse effects on body weight or spleen size.
Conclusion: These findings indicate that BKT300 exerts anti inflammatory effects primarily by inhibiting immune cell migration through disruption of cytoskeletal dynamics and support its further development for immune mediated inflammatory disorders.
