S3I-201, also known as NSC 74859, is a cell-permeable Stat3 inhibitor that binds to the Stat3-SH2 domain, prevents Stat3 phosphorylation/activation, dimerization, and DNA-binding.
CAS Number: 501919-59-1
Molecular Weight: 365.36
Chemical Name: 2-hydroxy-4-(2-(tosyloxy)acetamido)benzoic acid
Appearance: Solid Power.
Purity: ≥98% (or refer to the Certificate of Analysis)
Solubility: DMSO: 25 mg/mL
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis
Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.
Shelf Life: ≥12 months if stored properly.
Stock Solution Storage: 0 - 4 oC for 1 month or refer to the Certificate of Analysis.
Drug Formulation: To be determined.
HS Tariff Code: 382200
How to use
S3I-201 (NSC-74859) preferentially inhibits Stat3 DNA-binding activity over that of Stat1 (IC50 values, Stat3•Stat3, 86±33 μM; Stat1•Stat3, 160±43 μM; and Stat1•Stat1, >300 μM) and inhibits that of Stat5 with IC50 of 166±17 μM). S3I-201 significantly reduces viable cell numbers and inhibits growth of transformed mouse fibroblasts NIH 3T3/v-Src and breast carcinoma cell lines (MDA-MB-231, MDA-MB-435, and MDA-MB-468). At 30-100 μM, S3I-201 induces significant apoptosis in the representative human breast carcinoma cell line MDA-MB-435 and NIH 3T3/v-Src, both of which harbor constitutively active Stat3. The breast carcinoma MDA-MB-435 cell line is more sensitive to 30 μM S3I-201. By contrast, the human breast cancer MDA-MB-453 cells and the normal mouse fibroblasts (NIH 3T3), which do not contain abnormal Stat3 activity, are less sensitive to S3I-201 at 100 μM or less. At 300 μM or higher, S3I-201 induced general, nonspecific cytotoxicity independent of Stat3 activation status. Huh-7 cells do not express β2SP or TBGFR2 and are sensitive to STAT3 inhibition, with an IC50 of 100 μM for S3I-201, regardless of CD133+ status. The IC50 of S3I-201 is 150 μM for Huh-7 and SNU-398 cells, 15 μM for SNU-475 cells and 200 μM for SNU-182 cells. S3I-201 inhibits breast carcinoma MDA-MB-435, MDA-MB-453 and MDA-MB-231 cell lines with an IC50 close to 100 μM.
Human breast (MDA-MB-231) tumor-bearing mice are given an i.v. injection of S3I-201 (NSC-74859) or vehicle every 2 or every 3 days for 2 weeks, and tumor measurements are taken every 2-3 days. Compared with control (vehicle-treated) tumors, which continued to grow, human breast tumors in mice that received S3I-201 display strong growth inhibition. Continued evaluation of treated mice on termination of treatment shows no resumption of tumor growth, suggesting potentially a long-lasting effect of S3I-201 on tumor growth. Compared with vehicle-treated control tumors (n=15), which continued to grow, S3I-201 treatment of somatotroph tumor xenografts (n=15) significantly attenuated tumor growth for the duration of the experiment. Tumors derived from S3I-201-treated rats are significantly smaller than those from the untreated group (220±16 mm3 vs. 287±16 mm3, P<0.01) as early as 5 days after S3I-201 injection. Fifteen days after treatments, the average tumor volume of S3I-201-treated rats is 64% of that of controls (449±40 mm3 vs. 708±83 mm3, P<0.01). Rats are sacrificed and tumors are harvested 15 days after treatment initiation. The average tumor weight of S3I-201-treated rats is 78±8 mg, while tumors derived from control rats weighed 114±13 mg (32% reduction; P<0.05).
- Siddiquee K, et al. Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity. Proc Natl Acad Sci U S A. 2007 May 1;104(18):7391-6.
- Lin L, et al. The STAT3 inhibitor NSC 74859 is effective in hepatocellular cancers with disrupted TGF-β signaling. Oncogene. 2009 Feb 19;28(7):961-72.
- Zhou C, et al. STAT3 upregulation in pituitary somatotroph adenomas induces growth hormone hypersecretion. J Clin Invest. 2015 Apr;125(4):1692-702.
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