XY-280

XY-280 is a novel, brain-penetrant small-molecule inhibitor of the ST2 receptor (interleukin-1 receptor like-1, IL-1RL1). Developed to target the IL-33/ST2 signaling axis, it aims to mitigate neuroinflammation and brain damage associated with status epilepticus and epilepsy. In preclinical studies, XY-280 demonstrated a high brain-to-plasma ratio (up to 29.7) and a plasma half-life of approximately 11.9 hours. Treatment with the compound significantly reduced inflammatory cytokines, chemokines, and reactive gliosis in mouse models of LPS-induced neuroinflammation and pilocarpine-induced status epilepticus, suggesting potential as a disease-modifying therapy for epilepsy and other neuroinflammatory conditions.