RIPK1-IN-32 is an RIPK inhibitor with anti-inflammatory properties. It inhibits nitric oxide (NO) release, with an IC50 of 3.26 μM. Additionally, RIPK1-IN-32 disrupts the RIPK1/NF-κB/MAPK signaling pathway, preventing nuclear translocation of p65 and c-fos, leading to reduced expression of TNF-α and IL-6 and significantly alleviating acute liver injury related to sepsis. This compound is useful for studies on acute liver injury and sepsis.

RIPK1-IN-32 (Compound 12) significantly inhibits the thermal degradation of RIPK1 in RAW264.7 macrophages at concentrations of 0-25 μM and temperatures of 45-63 ℃. At 2.5 μM, it notably reduces the nuclear translocation of p65 and c-fos in RAW264.7 macrophages. Concentrations between 0.625-2.5 μM over 8 hours significantly decrease IL-6 and TNF-α levels in RAW 264.7 cells. Furthermore, RIPK1-IN-32 effectively inhibits the activation of the LPS-induced RIPK1/NF-κB/MAPK pathway at 0.625-2.5 μM for 8 hours.

RIPK1-IN-32 (Compound 12) administered intravenously at doses of 1.25-5 mg/kg (single dose) offers significant protection against liver, lung, and kidney damage in mice with LPS-induced sepsis.