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].
STAT3-IN-1 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Bone marrow-derived MDSCs
1μM
48 h
To evaluate the effect of STAT3-IN-1 on MDSCs-mediated suppression of CD8+ T cell activation and proliferation, results showed that STAT3-IN-1 enhanced CD8+ T cell activation and proliferation.
Theranostics. 2022 Jan 1;12(2):842-858.
Gr-1+ cells
1μM
48 h
To evaluate the effect of STAT3-IN-1 on GM-CSF-induced ROS and PD-L1 expression in Gr-1+ cells, results showed that STAT3-IN-1 inhibited ROS and PD-L1 expression.
Theranostics. 2022 Jan 1;12(2):842-858.
Bone marrow cells
1μM
48 h
To evaluate the effect of STAT3-IN-1 on GM-CSF-induced MDSCs expansion, results showed that STAT3-IN-1 inhibited MDSCs expansion.
Theranostics. 2022 Jan 1;12(2):842-858.
mEB8-ER cells
5 μM
5 days
Inhibition of STAT3 decreases mEB8-ER cell differentiation into neutrophils while promoting differentiation into monocytes/macrophages.
Cell Death Discov. 2023 Jul 28;9(1):274.
porcine chondrocytes
5 μM
4 days
To investigate the effect of STAT3-IN-1 on CDKN2A expression in porcine chondrocytes, results showed that STAT3-IN-1 reduced CDKN2A expression.
Front Immunol. 2025 Jan 14;15:1470907.
STAT3-IN-1 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
MC38 tumor model
Intraperitoneal injection
0.2 mg/kg
Every 3 days for 21 days
To evaluate the effect of Mithramycin A combined with gemcitabine on tumor growth, results showed that the combination treatment significantly suppressed tumor growth and reduced MDSCs infiltration.
Theranostics. 2022 Jan 1;12(2):842-858.
Mice
6-week-old male mice
Intraperitoneal injection
10 mg/kg
Every 2 days for 7 days
STAT3-IN-1 treatment reduced the number of neutrophils in the peripheral blood of mice while increasing the number of macrophages.
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