ST2825

Orally active peptidomimetic MyD88 homodimerization inhibitor with in vitro and in vivo efficacy against IL-1R and TLR9-dependent processes.

ST2825 is an orally active peptidomimetic of a heptapeptide structure in the MyD88 TIR BB-loop. ST2825 prevents IL-1beta-mediated activation of NF-kappaB by blocking MyD88 homodimerization and thereby the recruitment of IL-1 receptor-associated kinases IRAK1/4. ST2825 at 10 µg/mL completely suppresses 2.5 µg/mL TLR9 ligand ODN 2006-induced B-cell plasma cell differentation and antibodies production from PBMCs. ST2825 inhibits IL-1β-induced IL-6 production in mice (100 & 200 mg/kg p.o. prior to 20 µg/kg IL-1β i.p.) and protects against left ventricular (LV) dilatation and hypertrophy (25 mg/kg/day i.p.) in a murine model of nonreperfused acute myocardial infarction (AMI) in vivo.