STAT3-IN-46 is a selective, orally active inhibitor of the signal transducer and activator of transcription 3 (STAT3), with a KD value of 323.3 nM. It binds directly to the SH2 domain of STAT3, inhibiting the IL-6/JAK/STAT3 signaling pathway with an IC50 value of 0.87 μM, and decreases levels of c-Myc and Bcl-2. STAT3-IN-46 is applicable in cancer research, including studies on triple-negative breast cancer.

STAT3:323.3 nM (Kd)

STAT3-IN-46 (Compound W36) exhibits anti-proliferative activity in MDA-MB-231 and MDA-MB-468 cells with IC50 values of 0.61 and 0.65 μM, respectively. It shows minimal cytotoxic effects in HEK293 and HK2 cells, with IC50 values of 1.87 and 1.73 μM. STAT3-IN-46 inhibits the IL-6/JAK/STAT3 signaling pathway in HEK-Blue-IL-6 cells, with an IC50 of 0.87 μM. Additionally, STAT3-IN-46 (2.5-10 μM, 6-12 h) reduces phosphorylation levels of STAT3 in MDA-MB-231 and MDA-MB-468 cells. Furthermore, STAT3-IN-46 (2.5-10 μM, 24 h) downregulates c-Myc and Bcl-2 levels in MDA-MB-231 and MDA-MB-468 cells.

STAT3-IN-46 (Compound W36) effectively inhibits tumor growth in an MDA-MB-231 xenograft mouse model when administered via intraperitoneal injection at doses of 7.5-10 mg/kg or orally at 100 mg/kg, once daily for a duration of 16 days.