STAT3-IN-7 is a model of sorafenib that effectively inhibits STAT3 phosphorylation. STAT3-IN-7 causes apoptosis (apoptosis) through SHP-1-dependent STAT3 inactivation, does not regulate switch activity, and has anti-neoplastic activities.

Physicochemical Properties

Molecular Formula	C21H13CLF3N3O2
Molecular Weight	431.80
Exact Mass	431.064
CAS #	1313019-65-6
PubChem CID	53327725
Appearance	White to off-white solid powder
LogP	6
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	4
Heavy Atom Count	30
Complexity	623
Defined Atom Stereocenter Count	0
SMILES	ClC1C=CC(NC(=O)NC2C=CC(OC3C=CC(C#N)=CC=3)=CC=2)=CC=1C(F)(F)F
InChi Key	HVPZDXDXIQZKHU-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H13ClF3N3O2/c22-19-10-5-15(11-18(19)21(23,24)25)28-20(29)27-14-3-8-17(9-4-14)30-16-6-1-13(12-26)2-7-16/h1-11H,(H2,27,28,29)
Chemical Name	1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[4-(4-cyanophenoxy)phenyl]urea
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

ln Vitro	All evaluated breast cancer cells exhibited a dose-dependent decrease of cell survival following treatment with STAT3-IN-7 (SC-1; 1–10 μM; 48 hours) [1]. Strong apoptotic activity is induced when breast cancer cells are treated with STAT3-IN-7 (SC-1; 1–10 μM; 36 hours) [1]. In breast cancer cell lines, STAT3-IN-7 (SC-1; 1-10 μM; 36 hours) treatment demonstrated dose-dependent downregulation of p-STAT3 and its downstream proteins, cyclin D1 and survivin [1].
ln Vivo	STAT3-IN-7 (10 mg/kg; oral gavage; daily; for 28 days; female NCr athymic nude mice) therapy revealed substantial anticancer efficacy and p-STAT3 in MDA-MB-468 xenograft tumors Downregulation[1].
Cell Assay	Cell viability assay[1] Cell Types: HCC-1937, MDA-MB-231, MDA-MB-468, MDA-MB-453, SK-BR3 and MCF-7 Cell Tested Concentrations: 1 μM, 2 μM, 5 μM, 7.5 μM, 10 μM Incubation Duration: 48 hrs (hours) Experimental Results: Dose-dependent inhibition of cell viability was shown in all breast cancer cells tested. Apoptosis analysis[1] Cell Types: HCC-1937, MDA-MB-231, MDA-MB-468, MDA-MB-453, SK-BR3 and MCF-7 Cell Tested Concentrations: 1 μM, 2 μM, 5 μM , 7.5 μM, 10 μM Incubation Duration: 36 hrs (hours) Experimental Results: Induces effective apoptotic activity. Western Blot Analysis[1] Cell Types: HCC-1937, MDA-MB-231, MDA-MB-468, MDA-MB-453, SK-BR3 and MCF-7 Cell Tested Concentrations: 1 μM, 2 μM, 5 μM, 7.5 μM, 10 μM Incubation Duration: 36 hrs (hours) Experimental Results: p-STAT3 and its downstream proteins cyclin D1 and survivin were downregulated in a dose-dependent manner in breast cancer cell lines.
Animal Protocol	Animal/Disease Models: Female NCr athymic nude mice (4-6 weeks old) were injected with breast cancer cells [1] Doses: 10 mg/kg Route of Administration: po (oral gavage); daily; lasted for 28 days. Experimental Results: In MDA-MB- 468 demonstrated potent antitumor activity and p-STAT3 downregulation in xenograft tumors.
References	[1]. Novel sorafenib analogues induce apoptosis through SHP-1 dependent STAT3 inactivation in human breast cancer cells. Breast Cancer Res. 2013;15(4):R63.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~578.97 mM)

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.3159 mL	11.5794 mL	23.1589 mL
	5 mM	0.4632 mL	2.3159 mL	4.6318 mL
	10 mM	0.2316 mL	1.1579 mL	2.3159 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.