A novel indazole derivative, compound Cyy-272, attenuates LPS-induced acute lung injury by inhibiting JNK phosphorylation

Highlights: • Cyy-272, a newly synthesized indazole compound, exhibit anti-inflammatory activity in LPS-stimulated macrophage. • In vivo, Cyy-272 can relieve inflammatory reaction and improve tissue injury in LPS-induced Acute Lung Injury. • Cyy-272 exerts anti-inflammatory activity by inhibiting the LPS-induced phosphorylation of JNK. Acute lung injury (ALI) is a diffuse lung dysfunction disease characterized by high prevalence and high mortality. Thus far, no effective pharmacological treatment has been made for ALI in clinics. Inflammation is critical to the development of ALI. Therefore, anti-inflammation may be a potential therapy strategy for ALI. Indazole-containing derivatives, representing one of the most important heterocycles in drug molecules, are endowed with a broad range of biological properties, such as anti-cancer and anti-inflammation. In the current study, we investigated the biological effects of Cyy-272, a newly synthesized indazole compound, on LPS-induced ALI both in vivo and in vitro. Results show that Cyy-272 can inhibit the release of inflammatory cytokines in LPS-stimulated macrophage and alleviate LPS induced ALI. Further experiment revealed that Cyy-272 exhibit anti-inflammation activity by inhibiting JNK phosphorylation. Overall, our studies show that an indazole derivative, Cyy-272, is effective in suppressing LPS-induced JNK activation and inflammatory signaling.