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 .
Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic protein that plays important roles in oncogenic signaling pathways. STAT3-IN-1 (compound 7d) is a potent, 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. Exposing MDA-MB-231 cells to STAT3-IN-1 (1-5 μM) for 48 h led to dose-dependent inhibition of STAT3 acetylation at Lys685 residue. STAT3-IN-1 increased the expressions of the tumor-suppressor genes which were related to STAT3 acetylation at Lys685, thereby further demonstrated that STAT3-IN-1 inhibited STAT3 acetylation. In MDA-MB-231 cancer cells, STAT3-IN-1 (1-5 μM for 48 hr) markedly decreased the phospho-Tyr705 STAT3 in a dose-dependent manner without affecting the total STAT3, indicating that STAT3-IN-1 selectively decreased the level of p-STAT3. STAT3-IN-1 (1-10 μM for 48 hr) dose-dependently inhibited the proliferation of STAT3 dependent MDA-MB-231 cells. STAT3-IN-1 (10 mg/kg, 20 mg/kg) significantly inhibited tumor growth as reflected in decreased tumor weight. And the level of p-STAT3 (Y705) was also inhibited in tumor tissues from mice treated with STAT3-IN-1[2].
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