RIPA-56

RIPA-56 is a highly potent, selective, and metabolically stable inhibitor of receptor-interacting protein 1 (RIP1) with an IC₅₀ of 13 nM. RIPA-56 can be used for the treatment of systemic inflammatory response syndrome^[1]. IC50 & Target: IC50: 13 nM (RIP1)^[1] In Vitro: RIPA-56 shows efficient inhibition of RIP1 kinase activity, with an IC₅₀ of 13 nM and no inhibition of RIP3 kinase activity at a 10 μM concentration. RIPA-56 also demonstrates potency in protection of murine L929 cells from TNFα/z-VAD-FMK (TZ)-induced necrosis (EC₅₀=27 nM)^[1]. In Vivo: In the SIRS mice disease model, RIPA-56 efficiently reduces tumor necrosis factor alpha (TNFα)-induced mortality and multi-organ damage. Compared to known RIP1 inhibitors, RIPA-56 is potent in both human and murine cells, is much more stable in vivo, and is efficacious in animal model studies. RIPA-56 has an impressive PK profile in mice with a 3.1 h half-life, 22% oral bioavailability (P.O.), and 100% bioavailability from intraperitoneal injection (I.P.)^[1].