EX26

Descriptions

Biochem/physiol Actions

Ex26 is a peripherally-restricted biphenylcarboxamide derivative that acts as a highly potent and subtype-selective S1P1 antagonist (IC₅₀?= 0.93 nM against S1PR1 and >3.1 µM against S1PR2/3/4/5). Ex26 significantly elevates CpG-A-stimulated interferon (IFN) production in plasmacytoid dendritic cell culture (10 µM) and prevents S1P1?agonist-induced S1P1?receptor?internalization and polyubiquitinylation in HEK cells (0.1-1,000 nM). Ex26 induces lymphocyte sequestration (ED₅₀?= 0.06 mg/kg, i.p.) in lymph nodes and pulmonary edema (2 hr post 30 mg/kg i.p.) in mice, leading to the inhibition of lymphocyte and thymocyte egress (0.1 mg/kg/hr continuously for 3 days after a loading dose of 3 mg/kg). Ex26 has been shown to ameliorate experimental autoimmune encephalomyelitis (EAE) in a mouse MS model and elevate CpG-A-stimulated serum IFN upregulation in mice?in vivo?(30 mg/kg/d, i.p.).

Packaging

5, 25 mg in glass bottle