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

Jh-X-119-01 at a concentration of 10 μM effectively reduces NF-κB phosphorylation and decreases the mRNA expression levels of IL-6 and TNFα in LPS-stimulated macrophages in vitro, demonstrating its anti-inflammatory properties. This compound also specifically targets and inhibits IRAK1 phosphorylation. Employing Western Blot analysis in both RAW 264.7 and THP-1 cell lines, it was observed that a 15-minute incubation with Jh-X-119-01 significantly diminished LPS (100 ng/mL)-induced phosphorylation of IκBα and NF-κB-P65, further confirming its mechanism of action.

Jh-X-119-01 enhances survival rates and reduces immunological pathologies in LPS-challenged mice, with efficacy depending on dosage. Administered intraperitoneally to C57BL/6 male mice weighing 20-22 grams, a 5 mg/kg dose significantly increases survival, with further improvements seen at 10 mg/kg. This compound provides protection against LPS-induced sepsis; control mice treated with vehicle experienced a survival rate of 13.3% after 5 days, whereas survival rates for mice treated with 5 mg/kg and 10 mg/kg of Jh-X-119-01 were 37.5% and 56.3%, respectively.