STAT3-IN-15 is a potent, orally bioactive STAT3 inhibitor against idiopathic pulmonary fibrosis (IPF). STAT3-IN-15 inhibits STAT3 phosphorylation. STAT3-IN-15 also inhibits TGF-β1-induced epithelial cell migration and deformation and inhibits epithelial-mesenchymal transition (EMT).

Physicochemical Properties

Molecular Formula	C20H17F3N2O3S
Molecular Weight	422.42
Appearance	Off-white to light yellow solid powder
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	STAT3
ln Vitro	Compound 10k, STAT3-IN-15, has an IC50 of 0.47 μM, which reduces the growth of NIH-3T3 cells [1]. STAT3-IN-15 resides in the pY subpocket of STAT3 and makes hydrogen bonds with Ser636 and Lys591. [1]. Inhibiting fibroblast activation and proliferation, STAT3-IN-15 (0-100 nM, 72 h) [1]. NIH-3T3 cells' activation mediated by TGF-β1 (5 ng/mL) is inhibited by STAT3-IN-15 (50 nM, 24 h) [1]. In A549 cells, TGF-β1-induced EMT (morphological alterations) is blocked by STAT3-IN-15 (200 nM, 24 hours) [1].
ln Vivo	When given by gavage, STAT3-IN-15 (Compound 10k) (30 and 60 mg/kg) reduces the lung fibrosis that Bleomycin (HY-108345) causes in mice [1].
Cell Assay	Cell Viability Assay[1] Cell Types: NIH-3T3 cells Tested Concentrations: 0, 6.25, 12.5, 25, 50, 100 nM Incubation Duration: 72 h Experimental Results: Inhibited NIH-3T3 cell viability dose-dependently. Western Blot Analysis[1] Cell Types: NIH-3T3 cells Tested Concentrations: Inhibited NIH-3T3 cell viability dose-dependently. Incubation Duration: 24 h Experimental Results: Inhibited the expression of α-SMA and collagen I and the phosphorylation of STAT3.
Animal Protocol	Animal/Disease Models: BLM-induced pulmonary fibrosis mouse model[1] Doses: 30 and 60 mg/kg Route of Administration: intragastric (po) administration Experimental Results: Recovered the lung structure and decreased the hydroxyproline content. decreased the expression of the p-Stat3Ty705 protein in the lung tissue . Improved BLM-induced imbalance of immune microenvironment.
References	[1]. Discovery of the novel Benzo[b]thiophene 1,1-dioxide derivatives as a potent STAT3 inhibitor against idiopathic pulmonary fibrosis. Eur J Med Chem. 2022 Nov 28;246:114953.

Solubility Data

Solubility (In Vitro)

DMSO :~100 mg/mL (~236.73 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.92 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.3673 mL	11.8366 mL	23.6731 mL
	5 mM	0.4735 mL	2.3673 mL	4.7346 mL
	10 mM	0.2367 mL	1.1837 mL	2.3673 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.