JH-X-119-01 hydrochloride is a potent and selective inhibitor of interleukin-1 receptor-associated kinases 1 (IRAK1). It effectively alleviates lipopolysaccharide (LPS)-induced sepsis in mice.

Jh-X-119-01 (10 μM) decreases phosphorylation of NF-κB and mRNA levels of IL-6 and TNFα in LPS-treated macrophages in vitro. Jh-X-119-01 selectively inhibits IRAK1 phosphorylation[1]. Western Blot Analysis[1]Cell Line: RAW 264.7 cells and THP-1 cells Concentration: 10 μM Incubation Time: 15 minutes Result: Decreased LPS (100 ng/mL)-induced phosphorylation of IκBα and NF-κB-P65.

Jh-X-119-01 improves survival and decreases immunopathies of LPS-challenged mice. Jh-X-119-01 increases survival of mice at the dose of 5 mg/kg body weight. Survival is further improved when the dose is increased to 10 mg/kg[1]. Animal Model: C57BL/6 (20-22 g, male) mice[1]Dosage: 5 mg/kg and 10 mg/kg Administration: Intraperitoneally injected; 5 days Result: Protected mice from LPS (20 mg/kg)-induced sepsis. Survival at day 5 was 13.3% in control group where septic mice were treated by vehicle, while the values were 37.5% and 56.3% for 5 mg/kg and 10 mg/kg.