CKD-712

CKD-712 is an orally active multi-target tetrahydroisoquinoline derivatived and a potent inhibitor of the NF-κB pathway^[2]. CKD-712 selectively inhibits MMP-9 with no effect on MMP-2, downregulates the expression of TNF-α, IL-6, cyclin A, cyclin B, CDK-1 and other proteins, and activates the PI3K/Akt signaling pathway^[1][2]. CKD-712 blocks the activation and nuclear translocation of NF-κB, downregulates inflammatory factors and pro-tumor metastatic proteins, and induces G2/M phase arrest in tumor cells and thereby inhibits the invasion of cancer cells^[1][2]. CKD-712 can be used for the research of sepsis, myocardial ischemia-reperfusion injury and non-small cell lung cancer^[1][2][3]. In Vitro:CKD-712 (5-30 μg/mL; 48 h) dose-dependently suppresses proliferation of A549 human lung adenocarcinoma cells, with 30 μg/mL inhibiting proliferation by 60% without inducing cell death^[2].
CKD-712 (30-50 µg/ml; 48 h) induces G2/M cell cycle arrest in A549 cells^[2].
CKD-712 (30 µg/ml; 48 h) suppresses cyclin A, cyclin B and CDK-1 expression in A549 human lung cancer cells^[2].
CKD-712 (30 µg/ml; 48 h) dose-dependently inhibits mitosis in A549 human lung carcinoma cells^[2].
CKD-712 (20 µg/ml; 12 h, 24 h) inhibits adenocarcinoma cell growth^[2].
CKD-712 (10 µg/ml; 1 h; pre-incubation) inhibits TNF-α-induced NF-κB activation in A549 human lung carcinoma cells^[2].
CKD-712 (5-30 µg/ml; 24 h) suppressed proteins involved in proliferation, anti-apoptosis, and angiogenesis in A549 human lung carcinoma cells^[2].
CKD-712 (30 µg/ml; 48 h) dose-dependently inhibits MMP-9 activity in A549 human lung carcinoma cells without affecting MMP-2 activity^[2].
In Vivo:CKD-712 (1-20 mg/kg; i.p.; single dose; 30 min pre-LPS) dose-dependently prevents LPS-induced hypothermia in mice, maintaining significantly higher body temperatures at 5 and 7 hours post-LPS challenge^[1].
CKD-712 (1-3 mg/kg/day; i.p.; once daily; 4 total doses) improves survival in CLP-induced polymicrobial septic mice, with a 50% survival rate observed at 1 mg/kg/day administered over 4 days^[1].
CKD-712 (2.5-20 mg/kg; i.p.; two doses (24 hours and 1 hour pre-LPS)) dose-dependently reduces markers of liver and kidney injury in LPS-induced DIC rats, with the greatest reduction in GOT (117.8 U/L) and BUN (11.8 mg/dL) observed at 20 mg/kg^[1].
CKD-712 (20 mg/kg; i.p.; two doses (24 hours and 1 hour pre-LPS)) protects against LPS-induced histological damage to the liver and lung in DIC rats, reducing inflammatory cell infiltration and tissue necrosis^[1].
CKD-712 (1-20 mg/kg; i.p.; single dose) dose-dependently improves survival in LPS-induced septic mice, with up to 92% survival observed at 5 and 10 mg/kg when administered 30 minutes pre-LPS^[1].
CKD-712 (5-20 mg/kg; i.p.; single dose; 30 min pre-zymosan) improves survival in zymosan-induced septic mice, with a 67% survival rate observed at 20 mg/kg when administered 30 minutes pre-zymosan^[1].
CKD-712 (2.5-20 mg/kg; i.p.; two doses (24 hours and 1 hour pre-LPS)) dose-dependently suppresses LPS-induced systemic inflammation in DIC rats, with the greatest reduction in TNF-α (85.5 pg/mL) observed at 10 mg/kg^[1].
CKD-712 (20 mg/kg; i.p.; two doses (24 hours and 1 hour pre-LPS)) inhibits LPS-induced NF-κB translocation to the nucleus in lung pneumocytes of DIC rats, reducing pro-inflammatory signaling^[1].