Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) are serious and devastating pulmonary manifestations of acute systemic inflammation with high morbidity and mortality worldwide. Currently, there are no specific effective treatments for ALI/ARDS. RIPK1, which contributes to necroptosis and inflammation, is confirmed to be a promising strategy for the treatment of ALI. Herein, 23 benzothiazole derivatives were designed to specifically target RIPK1, and SZM-1209 showed high anti-necroptotic activity (EC50 = 22.4 nM) and kinase selectivity on RIPK1 over RIPK3 (Kd,RIPK1 = 85 nM, Kd,RIPK3 > 10,000 nM). In a mTNF-α-induced systemic inflammatory response syndrome (SIRS) model, SZM-1209 could completely reverse mouse deaths with significant anti-inflammatory effects. Furthermore, in a NNK short-term intratracheal exposure-induced ALI model, SZM-1209 significantly alleviated ALI by reducing pulmonary edema and pathological damage. Collectively, activities of SZM-1209 against RIPK1, necroptosis, SIRS, and ALI warranted further investigation of optimized benzothiazoles as promising lead structures against ALI-related diseases.
文章引用产品列表
-
- EK206
- ELISA试剂盒
Mouse IL-6 ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥1,600.00 – ¥10,800.00
-
- EK206HS
- ELISA试剂盒, 高敏试剂盒
Mouse IL-6 High Sensitivity ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥2,000.00 – ¥3,400.00
-
- EK201BHS
- ELISA试剂盒, 高敏试剂盒
Mouse IL-1β High Sensitivity ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥2,000.00 – ¥3,400.00
-
- EK201B
- ELISA试剂盒
Mouse IL-1β ELISA Kit 检测试剂盒(酶联免疫吸附法)
- ¥1,600.00 – ¥10,800.00