| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
S3I-201 (also called S3I201; NSC74859; S3I 201; NSC-74859) is a cell permeable and selective Stat3 inhibitor with potential anticancer activity. It inhibits Stat3 with an IC50 of 86±33 μM. S3I-201 shows potent inhibition of STAT3 DNA-binding activity with IC50 of 86 μM in cell-free assays, and exhibits low activity towards STAT1 and STAT5. In the in vitro Stat3 DNA-binding assay, S3I-201 showed potent inhibition of the Stat3 DNA-binding activity with an average IC50 of 86 μM. In the EMSA assay, S3I-201 selectively inhibited Stat3 DNA-binding activity over that of Stat1 and Stat5. It suppressed the complex formation of Stat1-Stat3 and Stat1-Stat1 with IC50 values of 160 and > 300 μM, respectively.
| Targets |
Stat3 (IC50 = 86 μM)
|
||
|---|---|---|---|
| ln Vitro |
Stat3 DNA-binding activity is preferentially inhibited by NSC 74859 (S3I-201) over Stat1 (IC50 values: Stat3•Stat3, 86±33 μM; Stat1•Stat3, 160±43 μM; and Stat1•Stat1, >300 μM), while Stat5 DNA-binding activity is inhibited with an IC50 of 166±17 μM). The proliferation of transformed mouse fibroblasts NIH 3T3/v-Src and breast carcinoma cell lines (MDA-MB-231, MDA-MB-435, and MDA-MB-468) is inhibited and the number of viable cells is dramatically reduced by NSC 74859. NSC 74859 significantly promotes apoptosis in the constitutively active Stat3-containing human breast cancer cell lines MDA-MB-435 and NIH 3T3/v-Src at concentrations between 30 and 100 μM. The MDA-MB-435 cell line exhibits increased sensitivity to 30 μM NSC 74859. On the other hand, the normal mouse fibroblasts (NIH 3T3) and the human breast cancer MDA-MB-453 cells are less sensitive to NSC 74859 at 100 μM or less because they do not exhibit aberrant Stat3 activation. NSC 74859 produced non-specific, overall cytotoxicity at 300 μM or above, regardless of Stat3 activation status[1]. Huh-7 cells, independent of CD133+ status, are susceptible to STAT3 inhibition and do not express β2SP or TBGFR2. The IC50 for NSC 74859 is 100 μM. In Huh-7 and SNU-398 cells, the IC50 of NSC 74859 is 150 μM; in SNU-475 and SNU-182 cells, it is 15 μM. With an IC50 near 100 μM, NSC 74859 inhibits the MDA-MB-435, MDA-MB-453, and MDA-MB-231 cell lines that are used to treat breast cancer[2].
|
||
| ln Vivo |
For two weeks, NSC 74859 (S3I-201) or a vehicle is injected intravenously (i.v.) into human breast (MDA-MB-231) tumor-bearing mice every two or three days. Tumor measurements are obtained every two to three days. Mice treated with S3I-201 for human breast cancers show significant growth suppression as compared to control (vehicle-treated) tumors, which did not stop growing. Following treatment termination, an ongoing assessment of the treated mice reveals no return of tumor growth, indicating that S3I-201 may have a long-lasting effect on tumor growth[1]. For the duration of the trial, S3I-201 treatment of somatotroph tumor xenografts (n=15) dramatically reduced tumor development in comparison with vehicle-treated control tumors (n=15), which kept growing. As early as five days following NSC 74859 injection, tumors derived from rats treated with NSC 74859 are significantly less than those from the untreated group (220±16 mm3 vs. 287±16 mm3, P<0.01). Rats treated with NSC 74859 had an average tumor volume that is 64% smaller than that of controls fifteen days after treatment (449±40 mm3 vs. 708±83 mm3, P<0.01). Fifteen days after the start of treatment, the rats are killed and the tumors are extracted. Rats treated with NSC 74859 had an average tumor weight of 78±8 mg, whereas tumors from control rats weighed 114±13 mg (32% reduction; P<0.05)[3].
Furthermore, NSC 74859 treatment of Huh-7 xenografts in nude mice significantly retarded tumor growth, with an effective dose of only 5 mg/kg. Moreover, NSC 74859 inhibited tyrosine phosphorylation of STAT3 in HCC cells in vivo. [2] In addition, S3I-201 attenuated somatotroph tumor growth and GH secretion in a rat xenograft model. [3] |
||
| Cell Assay |
Transient Transfection of Cells and Treatment with Compound. [1]
Twelve to 24 h after seeding, cells were transfected with the appropriate plasmids. For detailed procedure information, see SI Materials and Methods. Twenty-four hours after transfection, cells were untreated (0.05% DMSO) or treated with S3I-201 (100 μM) for an additional 24 h and harvested, and cytosolic extracts were prepared for luciferase assay, as described, or cells were analyzed by annexin V binding and flow cytometry. Soft-Agar Colony-Formation Assay.[1] Colony formation assays were carried out in six-well dishes, as described previously. Treatment with S3I-201 was initiated 1 day after seeding cells by adding 100 μl of medium with or without S3I-201 and repeating every 3 days, until large colonies were evident. Measurement of Apoptosis by Flow Cytometry. [1] Proliferating cells were treated with or without S3I-201 for up to 48 h. In some cases, cells were first transfected with Stat3C, ST3-NT, or ST3-SH2 domain or mock-transfected for 24 h before treatment with compound for an additional 24–48 h. Cells were then detached and analyzed by annexin V binding according to the manufacturer's protocol and flow cytometry to quantify the percent apoptosis. |
||
| Animal Protocol |
|
||
| References |
|
||
| Additional Infomation |
S3I-201 is an amidobenzoic acid obtained by formal condensation of the carboxy group of [(4-methylbenzene-1-sulfonyl)oxy]acetic acid with the amino group of 4-amino-2-hydroxybenzoic acid. It has a role as a STAT3 inhibitor. It is a monohydroxybenzoic acid, a tosylate ester and an amidobenzoic acid.
|
| Molecular Formula |
C16H15NO7S
|
|
|---|---|---|
| Molecular Weight |
365.36
|
|
| Exact Mass |
365.056
|
|
| Elemental Analysis |
C, 52.60; H, 4.14; N, 3.83; O, 30.65; S, 8.78
|
|
| CAS # |
501919-59-1
|
|
| Related CAS # |
|
|
| PubChem CID |
252682
|
|
| Appearance |
White to gray solid powder
|
|
| Density |
1.5±0.1 g/cm3
|
|
| Boiling Point |
654.7±55.0 °C at 760 mmHg
|
|
| Flash Point |
349.8±31.5 °C
|
|
| Vapour Pressure |
0.0±2.1 mmHg at 25°C
|
|
| Index of Refraction |
1.642
|
|
| LogP |
3.08
|
|
| Hydrogen Bond Donor Count |
3
|
|
| Hydrogen Bond Acceptor Count |
7
|
|
| Rotatable Bond Count |
6
|
|
| Heavy Atom Count |
25
|
|
| Complexity |
578
|
|
| Defined Atom Stereocenter Count |
0
|
|
| InChi Key |
HWNUSGNZBAISFM-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C16H15NO7S/c1-10-2-5-12(6-3-10)25(22,23)24-9-15(19)17-11-4-7-13(16(20)21)14(18)8-11/h2-8,18H,9H2,1H3,(H,17,19)(H,20,21)
|
|
| Chemical Name |
2-hydroxy-4-[[2-(4-methylphenyl)sulfonyloxyacetyl]amino]benzoic acid
|
|
| Synonyms |
|
|
| 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 Note: This product is not stable in solution, please use freshly prepared working solution for optimal results. |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 7.5 mg/mL (20.53 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 75.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 7.5 mg/mL (20.53 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 75.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 7.5 mg/mL (20.53 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 2.5 mg/mL (6.84 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 5: ≥ 2.5 mg/mL (6.84 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. 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. Solubility in Formulation 6: 5% DMSO, 95% PEG 300 :15 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7370 mL | 13.6851 mL | 27.3703 mL | |
| 5 mM | 0.5474 mL | 2.7370 mL | 5.4741 mL | |
| 10 mM | 0.2737 mL | 1.3685 mL | 2.7370 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
|
|---|
|
|
|
|---|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
