STAT3-IN-10 (A11) is an inhibitor of STAT3 that directly binds to STAT3 SH2 domain, inhibits tumor cell growth and induces apoptosis in cancer cells (IC 50 = 5.18 μM) [1].

STAT3:5.18 μM

STAT3-IN-10 (A11) has been evaluated for its anticancer efficacy, demonstrated by IC50 values of 0.67 μM, 0.77 μM, and 1.24 μM against breast cancer cell lines MDA-MB-231 and MDA-MB-468, and human liver carcinoma cell line HepG2, respectively, over a 48-hour period. It directly interacts with the STAT3 SH2 domain, inhibiting STAT3 phosphorylation and the activity of downstream proteins while maintaining selectivity against the tumor suppressor STAT1. Furthermore, at concentrations ranging from 0 to 4 μM over a 24-hour exposure, STAT3-IN-10 (A11) promotes apoptosis in cancer cells and induces a significant S phase arrest specifically in MDA-MB-231 cells. Analysis methods used include Cell Viability Assay and Western Blot Analysis, which showed a decrease in STAT3-Y705 phosphorylation and reduced expression of target genes like C-Myc and Cyclin D1, with minimal impact on STAT1 levels. Apoptosis and Cell Cycle Analysis confirmed induction of apoptosis and cell cycle arrest in a dose-dependent manner.

STAT3-IN-10 (A11) administered intraperitoneally (IP) at doses of 5 and 10 mg/kg once daily for 21 days effectively inhibited the growth of human xenograft tumors in vivo, as demonstrated in a study using five-week-old female BALB/c nude mice (16–18g) implanted with human breast cancer cells MDA-MB-231. The treatment did not result in significant body weight loss in the treated mice and also reduced the levels of phosphorylated STAT3 (p-STAT3) in the tumor tissues.