STAT3/NF-κB-IN-1 is a potent inhibitor of STAT3 and NF-κB, exhibiting IC50 values of 5.86 μM for STAT3 and 4.22 μM for NF-κB in 4 T1 cells. It induces apoptosis by upregulating key apoptotic regulators (caspases-3, 9, Bax) and downregulating Bcl-2 expression. STAT3/NF-κB-IN-1 shows significant anticancer activity against breast cancer cell lines and can reduce tumor volume in vivo. It is applicable for research in breast cancer.

NF-κB:4.22 μM

STAT3/NF-κB-IN-1 (Compound 12a) exhibits cytotoxicity against 4T1, MDA-MB-231, MDA-MB-468, and MCF-7 cells with IC50 values of 7.68, 1.53, 7.00, and 6.14 μM, respectively, after 72 hours. At a concentration of 10 μM for 24 hours, it significantly impedes the migration and invasion of 4T1 and MDA-MB-231 cells. When applied at 1-10 μM for 24-72 hours, it notably induces early apoptosis in MDA-MB-231 cells while activating caspase 3/9 and increasing Bax/Bcl-2. Additionally, at 1-5 μM for 48-96 hours, it significantly suppresses the expression of p-STAT3 and NF-κB.

In a mouse model of Ehrlich ascites carcinoma, STAT3/NF-κB-IN-1 (Compound 12a) administered subcutaneously at 40 mg/kg once daily for 12 days exhibits significant antitumor activity.