STX-0119
目录号 : GC67779STX-0119 是一种选择性的、具有口服活性的 STAT3 二聚抑制剂。STX-0119 抑制 STAT3 转录，IC50 为 74 μM。
Cas No.:851095-32-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
STX-0119 is a selective, orally active STAT3 dimerization inhibitor. STX-0119 inhibits STAT3 transcription with an IC50 of 74 μM[1].
STX-0119 (10-50 μM; 24 h) inhibits STAT3 dimerization through a direct interaction with the STAT3 protein and not via the modulation of upstream regulators such as JAK in HEK293 and MDA-MB-468 cells[1].
STX-0119 (10-50 μM; 24 h) reduces the expression of STAT3 target proteins[1].
Western Blot Analysis[1]
| Cell Line: | MDA-MB-468 cells |
| Concentration: | 10, 20 and 50 μM |
| Incubation Time: | 24 h |
| Result: | Reduced the expression of STAT3 target proteins, namely, c-myc, cyclin D1, and survivin, in a concentration-dependent manner. Did not suppress the expression of those STAT3-regulated oncoproteins. |
STX-0119 (160 mg/kg; oral gavage; daily for 4 days) inhibits SCC-3 tumor growth in mice[1].
The plasma concentration of STX-0119 (160 mg/kg; oral gavage) is maintained at >100 μg/mL (>260 μM), even at 8 h after administration[1].
| Animal Model: | Male BALB/cA-Ν/Ν nude mice, SCC-3 lymphoma xenograft model[1] |
| Dosage: | 160 mg/kg |
| Administration: | Oral gavage, daily for 4 days |
| Result: | Suppressed the growth of SCC-3 cells significantly on the fourth day. |
[1]. Matsuno K, et al. Identification of a New Series of STAT3 Inhibitors by Virtual Screening. ACS Med Chem Lett. 2010 Jul 13;1(8):371-5.
| Cas No. | 851095-32-4 | SDF | Download SDF |
| 分子式 | C22H14N4O3 | 分子量 | 382.37 |
| 溶解度 | 储存条件 | 4°C, protect from light | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6153 mL | 13.0763 mL | 26.1527 mL |
| 5 mM | 0.5231 mL | 2.6153 mL | 5.2305 mL |
| 10 mM | 0.2615 mL | 1.3076 mL | 2.6153 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
STX-0119, a novel STAT3 dimerization inhibitor, prevents fibrotic gene expression in a mouse model of kidney fibrosis by regulating Cxcr4 and Ccr1 expression
Physiol Rep 2020 Oct;8(20):e14627.PMID:33112058DOI:10.14814/phy2.14627.
Kidney fibrosis is a histological hallmark of chronic kidney disease (CKD) and is believed to be involved in the progression of CKD. Therefore, inhibition of kidney fibrosis is a potential strategy for slowing CKD progression. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is activated by interleukin-6 and is reported to be involved in fibrosis. Previously, S3I-201, an inhibitor of STAT3 phosphorylation, was shown to inhibit renal fibrosis in a mouse model, but its mechanism was not clarified completely. In this study, we investigated whether STX-0119, a new inhibitor of STAT3 dimerization, suppressed kidney fibrotic gene expression using a mouse model of kidney fibrosis and examined the underlying mechanisms. Kidney fibrosis was induced by unilateral ureteral obstruction (UUO), which was accompanied by upregulation of STAT3 target genes. STX-0119 administration suppressed the expression of fibrotic genes in UUO kidneys without affecting STAT3 phosphorylation. STX-0119 decreased Cxcr4 mRNA in cultured rat kidney fibroblasts and Ccr1 mRNA in blood cells from UUO mice, both of which are reported to be involved in the progression of kidney fibrosis. These results suggest that STX-0119 inhibits fibrotic gene expression in kidney by suppressing Cxcr4 and Ccr1 expression. This is the first report to indicate a part of the mechanism of the antifibrotic effects of a STAT3 inhibitor and suggests that STX-0119 may be a lead compound for the treatment of kidney fibrosis.
A novel STAT3 inhibitor, STX-0119, attenuates liver fibrosis by inactivating hepatic stellate cells in mice
Biochem Biophys Res Commun 2019 May 21;513(1):49-55.PMID:30935693DOI:10.1016/j.bbrc.2019.03.156.
Liver fibrosis is characterized by formation of scar tissue in the liver. The role of STAT3 signaling has been implicated on activating hepatic stellate cells (HSC) to myofibroblast-like cells in liver fibrosis. Major factors that activate STAT3 signaling are TGF-β1 and IL-6, which are upregulated in the liver in patients afflicted with liver fibrosis. Recent reports indicate that not only IL-6, but also the non-canonical signaling pathway of TGF-β1 is associated with STAT3 signaling. In this study, we demonstrate a new function of the STAT3 inhibitor, STX-0119, in liver fibrosis. STX-0119 is an inhibitor of STAT3 dimerization, which is required for nuclear localization of STAT3. We first investigated the anti-fibrotic effect of STX-0119 in in vitro experiments. Exposure to STX-0119 inhibited the nuclear localization of STAT3 in HSCs, resulting in decreased expression of its target genes, such as col1a1 and αSMA. In addition, STX-0119 also inhibited the TGF-β1/IL-6-induced activation of HSCs. Next, we examined the in vivo effect of STX-0119 in the liver fibrosis mouse model using thioacetamide (TAA) and carbon tetrachloride (CCl4). STX-0119 attenuated the TAA-induced liver fibrosis by inhibiting activation of HSCs to myofibroblast-like cells. Consistent with the in vivo results using TAA-induced liver fibrosis model, treatment of STX-0119 similarly attenuated CCl4-induced liver fibrosis. In conclusion, we believe that STX-0119 inhibits the development of liver fibrosis by blocking the activation of hepatic stellate cells. These results indicate that STX-0119 is a potential new therapeutic strategy to prevent disease progression to cirrhosis.
Effect of the STAT3 inhibitor STX-0119 on the proliferation of a temozolomide-resistant glioblastoma cell line
Int J Oncol 2014 Jul;45(1):411-8.PMID:24820265DOI:10.3892/ijo.2014.2439.
Glioblastoma multiforme (GBM) is one of the most malignant and aggressive tumors and has a very poor prognosis, with a median survival time of less than 2 years. Once recurrence develops, there are few therapeutic approaches to control the growth of glioblastoma. In particular, temozolomide (TMZ)-resistant (TMZ-R) GBM is very difficult to treat, and a novel approach to overcome resistance is eagerly awaited. Previously, we reported a novel small molecule inhibitor of STAT3 dimerization, STX-0119, as a cancer therapeutic. In the current study, the efficacy of STX-0119 was evaluated against our established TMZ-resistant U87 cell line using quantitative PCR-based gene expression analysis, in vitro assay and animal experiments. The growth inhibitory effect of STX-0119 on U87 and TMZ-R U87 cells was moderate (IC₅₀, 34 and 45 µM, respectively). In particular, STX-0119 did not show significant inhibition of U87 tumor growth; however, it suppressed the growth of the TMZ-R U87 tumor in nude mice by more than 50%, and prolonged the median survival time compared to the control group. Quantitative PCR revealed that YKL-40, MAGEC1, MGMT, several EMT genes, mesenchymal genes and STAT3 target genes were upregulated, but most of those genes were downregulated by STX-0119 treatment. Furthermore, the invasive activity of TMZ-R U87 cells was significantly inhibited by STX-0119. YKL-40 levels in TMZ-R U87 cells and their supernatants were significantly decreased by STX-0119 administration. These results suggest that STX-0119 is an efficient therapeutic to overcome TMZ resistance in recurrent GBM tumors, and could be the next promising compound leading to survival prolongation, and YKL-40 may be a possible surrogate marker for STAT3 targeting.
Effect of the STAT3 inhibitor STX-0119 on the proliferation of cancer stem-like cells derived from recurrent glioblastoma
Int J Oncol 2013 Jul;43(1):219-27.PMID:23612755DOI:10.3892/ijo.2013.1916.
Signal transducer and activator of transcription (STAT) 3, a member of a family of DNA-binding molecules, is a potential target in the treatment of cancer. The highly phosphorylated STAT3 in cancer cells contributes to numerous physiological and oncogenic signaling pathways. Furthermore, a significant association between STAT3 signaling and glioblastoma multiforme stem-like cell (GBM-SC) development and maintenance has been demonstrated in recent studies. Previously, we reported a novel small molecule inhibitor of STAT3 dimerization, STX-0119, as a cancer therapeutic. In the present study, we focused on cancer stem-like cells derived from recurrent GBM patients and investigated the efficacy of STX-0119. Three GBM stem cell lines showed many stem cell markers such as CD133, EGFR, Nanog, Olig2, nestin and Yamanaka factors (c-myc, KLF4, Oct3/4 and SOX2) compared with parental cell lines. These cell lines also formed tumors in vivo and had similar histological to surgically resected tumors. STAT3 phosphorylation was activated more in the GBM-SC lines than serum-derived GB cell lines. The growth inhibitory effect of STX-0119 on GBM-SCs was moderate (IC50 15-44 µM) and stronger compared to that of WP1066 in two cell lines. On the other hand, the effect of temozolomide was weak in all the cell lines (IC50 53-226 µM). Notably, STX-0119 demonstrated strong inhibition of the expression of STAT3 target genes (c-myc, survivin, cyclin D1, HIF-1α and VEGF) and stem cell-associated genes (CD44, Nanog, nestin and CD133) as well as the induction of apoptosis in one stem-like cell line. Interestingly, VEGFR2 mRNA was also remarkably inhibited by STX-0119. In a model using transplantable stem-like cell lines in vivo GB-SCC010 and 026, STX-0119 inhibited the growth of GBM-SCs at 80 mg/kg. STX-0119, an inhibitor of STAT3, may serve as a novel therapeutic compound against GBM-SCs even in temozolomide-resistant GBM patients and has the potential for GBM-SC-specific therapeutics in combination with temozolomide plus radiation therapy.
The anti-tumor activity of the STAT3 inhibitor STX-0119 occurs via promotion of tumor-infiltrating lymphocyte accumulation in temozolomide-resistant glioblastoma cell line
Immunol Lett 2017 Oct;190:20-25.PMID:28716484DOI:10.1016/j.imlet.2017.07.005.
STAT3 is considered to be a key molecule to mediating tumor-induced immunosuppression in various manners at tumor sites, by acting through immune-regulatory cytokines derived from the tumor cells. Specific anti-STAT3 inhibitors have been developed using nude mouse models transplanted with human tumor cells. However, mouse systems cannot accurately represent the human immune response induced by STAT3 inhibitors, and more humanized therapeutic model based on human immune cells and tumors are needed. In the present study, an immune-deficient NOG mouse with the deletion of both MHC-class I and class II genes, an MHC-double knockout mouse (dKO-NOG), was developed and used to establish humanized immunotherapeutic model. We investigated the immunological effect of the STAT3 inhibitor STX-0119 against TMZ-resistant (TMZ-R) U87 glioma tumors by using humanized dKO-NOG mice. We compared the anti-tumor effects of STX-0119 between the nude and humanized dKO-NOG mouse models. An in vivo study using the nude mouse model showed that STX-0119 inhibited the growth of TMZR U87 tumors, but accumulation of tumor-infiltrating lymphocytes (TILs) were not promoted compared with the control levels. In contrast, STX-0119 inhibited tumor growth more rapidly and strongly in humanized dKO-NOG mice than in nude mice, and a large amount of TILs, mainly consisting of CD8+ T cells and macrophages, were found in the tumors. These results suggest that STX-0119 has anti-tumor activity occurring through the promotion of TIL accumulation at the tumor site and that humanized dKO-NOG mouse system may be a powerful tool to evaluate the effects of STAT3 inhibitors on human systems.