Ponesimod CAS# 854107-55-4 珀奈莫德

Ponesimod (ACT-128800) is a selective, orally active sphingosine-1-phosphate receptor 1 (S1P₁) modulator. In preclinical studies, it bound human S1P₁ with high affinity (Ki ~2.5 nM) and showed >10,000-fold selectivity over S1P₂–S1P₅ receptors. Ponesimod induced dose-dependent internalization and functional antagonism of S1P₁, leading to reversible lymphocyte sequestration. In rodent models of autoimmune disease, including experimental autoimmune encephalomyelitis, ponesimod significantly reduced disease severity and CNS inflammation. Pharmacokinetic studies demonstrated rapid absorption, good oral bioavailability, and dose-proportional exposure. Lymphocyte counts normalized after drug withdrawal, confirming its reversible mechanism. These findings supported its development for multiple sclerosis and immune-mediated disorders.