STAT3-IN-3 is a novel and potent inhibitor of signal transducer and activator of transcription 3 (STAT3) with anticancer activity. STAT3-IN-3 induces apoptosis in breast cancer cells as a promising mitochondria-targeting STAT3 inhibitor for cancer.
Physicochemical Properties
| Molecular Formula | C27H26BRN3O6S |
| Molecular Weight | 600.480844974518 |
| Exact Mass | 599.072 |
| CAS # | 2361304-26-7 |
| PubChem CID | 138454793 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 3.6 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 38 |
| Complexity | 1140 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | BrC1=CC=CC2=C1C=C(C(N1CCN(C(C3C(=O)OC4C=C(C=CC=4C=3)N(CC)CC)=O)CC1)=O)S2(=O)=O |
| InChi Key | LEVMMUZFAXTJOJ-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C27H26BrN3O6S/c1-3-29(4-2)18-9-8-17-14-20(27(34)37-22(17)15-18)25(32)30-10-12-31(13-11-30)26(33)24-16-19-21(28)6-5-7-23(19)38(24,35)36/h5-9,14-16H,3-4,10-13H2,1-2H3 |
| Chemical Name | 3-(4-(4-bromo-1,1-dioxidocinnamoyl)piperazine-1-carbonyl)-7-(diethylamino)-2H-chromen-2-one |
| Synonyms | STAT3 IN 3 STAT3 IN-3STAT3-IN-3 STAT3-IN 3 |
| 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 | The phosphorylation levels of STAT1, JAK2, Src, and Erk1/2 are unaffected by STAT3-IN-3 [1]. MDA-MB-231, HCT-116, HepG2, and MCF-7 cells are inhibited from growing by STAT3-IN-3, with IC50 values of 1.43 μM, 1.89 μM, 2.88 μM, and 3.33 μM, in that order [1]. Bcl-2 and Cyclin D1 are STAT3 target genes whose expression is transcribed via STAT3-IN-3 [1]. Casein phosphate STAT3-IN-3 decreases the DNA binding activity of STAT3, and STAT3-IN-3 inhibits STAT3 [1]. STAT3-IN-3 (1-4 μM; 24 hours) detects the caspase-9, caspase-3, and PARP pathways, which results in a significant drop in mitochondrial membrane potential and an increase in reactive oxygen species [1]. |
| ln Vivo | STAT3-IN-3 (10mg/kg -20mg/kg; intraperitoneal injection; once daily; for 14 days) possesses anti-tumor activity that is effective against the growth of 4T1 breast cancers at entry [1]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: MDA -MB-231 cells, HCT-116 cells, HepG2 cells, MCF-7 cells Tested Concentrations: MTT assay Incubation Duration: 48 hrs (hours) Experimental Results: demonstrated anti-proliferative activity. Apoptosis analysis [1] Cell Types: MDA-MB-231 Cell Tested Concentrations: 0 μM, 1 μM, 2 μM, 4 μM Incubation Duration: 24 hrs (hours) Experimental Results: Dose-dependent induction of apoptosis in MDA-MB-231 cells, and Apoptosis rates. Western Blot Analysis[1] Cell Types: MDA-MB-231 Cell Tested Concentrations: 0 μM, 1 μM, 2 μM, 4 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induction of caspase-9, caspase-3 and PARP cleavage. |
| Animal Protocol |
Animal/Disease Models: Adult female balb/c (Bagg ALBino) mouse (6 weeks old) [1] Doses: 10 mg/kg, 20 mg/kg Route of Administration: intraperitoneal (ip) injection, one time/day for 14 days Experimental Results: Dramatically inhibited tumor volume . |
| References |
[1]. Discovery of fluorescent coumarin-benzo[b]thiophene 1, 1-dioxide conjugates as mitochondria-targeting antitumor STAT3 inhibitors. Eur J Med Chem. 2019 Jul 15;174:236-251. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~5 mg/mL (~8.33 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 | 1.6653 mL | 8.3267 mL | 16.6533 mL | |
| 5 mM | 0.3331 mL | 1.6653 mL | 3.3307 mL | |
| 10 mM | 0.1665 mL | 0.8327 mL | 1.6653 mL |