STAT3-IN-1

STAT3-IN-1 (compound 7d) is an excellent, selective and orally active STAT3 inhibitor, with IC50 values of 1.82 μM and 2.14 μM in HT29 and MDA-MB 231 cells, respectively. STAT3-IN-1 (compound 7d) induces tumor apoptosis[1].

Signaling Pathways >> Stem Cell/Wnt >> STAT

Research Areas >> Cancer

Signaling Pathways >> JAK/STAT Signaling >> STAT

IC50: 1.82 μM (STAT3 in HT29 cells), 2.14 μM (STAT3 in MDA-MB 231 cells)[1].

STAT3-IN-1 (compound 7d: 0-10 μM, 48 h) inhibits the STAT3 acetylation at lysine 685 and affected its specific genes expressions[1]. STAT3-IN-1 (compound 7d: 0-10 μM, 48 h) induces tumor cells apoptosis in MDA-MB-231 cells[1]. Apoptosis Analysis[1] Cell Line: MDA-MB-231 cell lines. Concentration: 0-10 μM. Incubation Time: 48 hours. Result: The induced apoptosis rates (early and late apoptosis) at 1, 2, 5, 8 and 10 mM were 9.0%, 11.2%, 20.9%, 43.3% and 85.2% versus control 3.0%. Western Blot Analysis[1] Cell Line: MDA-MB-231 and HT-29 cell lines. Concentration: 0-10 μM. Incubation Time: 48 hours. Result: Inhibited STAT3 acetylation and STAT3 tyrosine phosphorylation in MDA-MB-231 cells. Increased the expressions of these tumor-suppressor genes (PTPN6 (SHP-1), CDKN2A and DLEC1) which were related to STAT3 acetylation at Lys685.

STAT3-IN-1 (compound 7d: 10, 20 mg/kg, two weeks) arrests tumor growth with low toxicity in mouse-xenograft model[1]. Animal Model: Mouse-xenograft model bearing inoculation of mice breast cancer 4T1 cells[1]. Dosage: 10, 20 mg/kg. Administration: Oral administration once every other day for two weeks. Result: Arrested tumor growth with no obvious body weight loss.

[1]. Li S, et al. Discovery of oral-available resveratrol-caffeic acid based hybrids inhibiting acetylated and phosphorylated STAT3 protein. Eur J Med Chem. 2016 Nov 29;124:1006-1018.