Home>>Signaling Pathways>> Others>> FAS>>Fatostatin

Fatostatin Sale

(Synonyms: 125B11) 目录号 : GC36031

An inhibitor of SREBP activation

Fatostatin Chemical Structure

Cas No.:125256-00-0

规格 价格 库存 购买数量
10mM (in 1mL DMSO)
¥653.00
现货
5mg
¥594.00
现货
10mg
¥900.00
现货
25mg
¥1,980.00
现货
50mg
¥3,420.00
现货
100mg
¥6,210.00
现货

电话:400-920-5774 Email: sales@glpbio.cn

Customer Reviews

Based on customer reviews.

Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

View current batch:

产品描述

Sterol regulatory element binding proteins (SREBPs) are transcription factors that have pivotal roles in lipogenesis and fat metabolism.1 The activation of SREBPs requires escort to the Golgi by SREBP cleavage-activating protein (SCAP) followed by proteolytic release of SREBP from the Golgi.2 Fatostatin is an inhibitor of SREBP activation, preventing SCAP-mediated escort of either SREBP-1 or SREBP-2 to the Golgi (IC50 = 5.6 ?M).3,4 This blocks constitutive SREBP-mediated gene expression in the human prostate cancer cell line DU145.3 Fatostatin prevents insulin-induced adipogenesis of 3T3-L1 cells as well as growth induced by insulin-like growth factor 1 in DU145 cells (IC50 = 0.1 ?M).5 Through its actions on SCAP/SREBP-1, it inhibits high glucose-induced upregulation of TGF-β in primary rat mesangial cells.6 This compound also alters lipid metabolism in vivo, reducing hepatic fat accumulation in ob/ob mice.3

[1].Horton, J.D., Goldstein, J.L., and Brown, M.S.SREBPs: Activators of the complete program of cholesterol and fatty acid synthesis in the liverJ. Clin. Invest.109(9)1125-1131(2002)

[2].Raghow, R., Yellaturu, C., Deng, X., et al.SREBPs: The crossroad of physiological and pathological lipid homeostasisTrends Endocrinol. Metab.19(2)65-73(2008)

[3].Kamisuki, S., Mao, Q., Abu-Elheiga, L., et al.A small molecule that blocks fat synthesis by inhibiting the activation of SREBPChem. Biol.16(8)882-892(2009)

[4].Kamisuki, S., Shirakawa, T., Kugimiya, A., et al.Synthesis and evaluation of diaryl thiazole derivatives that inhibit activation of sterol regulatory element-binding proteinsJ. Med. Chem.54(13)4923-4927(2011)

[5].Choi, Y., Kawazoe, Y., Murakami, K., et al.Identification of bioactive molecules by adipogenesis profiling of organic compoundsJ. Biol. Chem.278(9)7320-7324(2003)

[6].Uttarwar, L., Gao, B., Ingram, A.J., et al.SREBP-1 activation by glucose mediates TGF-? upregulation in mesangial cellsAm. J. Physiol. Renal Physiol.302(3)F329-F341(2012)

Chemical Properties

Cas No. 125256-00-0 SDF
别名 125B11
Canonical SMILES CCCC1=NC=CC(C2=NC(C3=CC=C(C)C=C3)=CS2)=C1
分子式 C18H18N2S 分子量 294.41
溶解度 DMSO: ≥ 27 mg/mL (91.71 mM); Water: < 0.1 mg/mL (insoluble) 储存条件 Store at -20°C
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。
Shipping Condition 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。

溶解性数据

制备储备液
1 mg 5 mg 10 mg
1 mM 3.3966 mL 16.9831 mL 33.9662 mL
5 mM 0.6793 mL 3.3966 mL 6.7932 mL
10 mM 0.3397 mL 1.6983 mL 3.3966 mL
  • 摩尔浓度计算器

  • 稀释计算器

  • 分子量计算器

质量
=
浓度
x
体积
x
分子量
 
 
 
*在配置溶液时,请务必参考产品标签上、MSDS / COA(可在Glpbio的产品页面获得)批次特异的分子量使用本工具。

计算

动物体内配方计算器 (澄清溶液)

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
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

Research Update

Fatostatin ameliorates inflammation without affecting cell viability

FEBS Open Bio 2022 Mar;12(3):594-604.PMID:35015380DOI:10.1002/2211-5463.13364.

The mature form of sterol regulatory element-binding protein (SREBP)1 is a transcription factor involved in lipid synthesis, which participates in toll like receptor 4-triggered inflammatory pathways during the resolution phase of inflammation in macrophages. SREBP1 has thus attracted interest as a candidate target molecule for ameliorating inflammation. Fatostatin is a small molecule that inhibits the maturation and function of SREBP, and its role in regulating inflammation is poorly understood. To evaluate the anti-inflammatory effect of Fatostatin, we compared body weight, footpad and hock dimensions, and arthritis scores between K/BxN serum-induced arthritis mice treated with Fatostatin and those treated with dimethyl sulfoxide as the vehicle control. We performed hematoxylin and eosin staining of joints of distal paws to assess tissue inflammation. Moreover, inflammatory cytokine production levels and cell viability were measured in lipopolysaccharide-responsive human embryonic kidney 293 cells (293/hTLR4A-MD2-CD14 cells) after Fatostatin administration. In K/BxN serum-induced arthritis mice, Fatostatin treatment significantly reduced the arthritis scores and hyperplasia. In vitro analysis revealed that Fatostatin significantly inhibited the secretion of inflammatory cytokines from cells activated with lipopolysaccharide, without affecting cell viability. This is the first study to demonstrate that Fatostatin is an anti-inflammatory agent that modulates the processing of lipid transcription factors without affecting cell viability. Accordingly, the study reveals the potential of anti-inflammatory therapeutics that link lipid regulation and inflammation.

Fatostatin reverses progesterone resistance by inhibiting the SREBP1-NF-κB pathway in endometrial carcinoma

Cell Death Dis 2021 May 26;12(6):544.PMID:34039951DOI:10.1038/s41419-021-03762-0.

Progesterone resistance can significantly restrict the efficacy of conservative treatment for patients with endometrial cancer who wish to preserve their fertility or those who suffer from advanced and recurrent cancer. SREBP1 is known to be involved in the occurrence and progression of endometrial cancer, although the precise mechanism involved remains unclear. In the present study, we carried out microarray analysis in progesterone-sensitive and progesterone-resistant cell lines and demonstrated that SREBP1 is related to progesterone resistance. Furthermore, we verified that SREBP1 is over-expressed in both drug-resistant tissues and cells. Functional studies further demonstrated that the inhibition of SREBP1 restored the sensitivity of endometrial cancer to progesterone both in vitro and in vivo, and that the over-expression of SREBP1 promoted resistance to progesterone. With regards to the mechanism involved, we found that SREBP1 promoted the proliferation of endometrial cancer cells and inhibited their apoptosis by activating the NF-κB pathway. To solve the problem of clinical application, we found that Fatostatin, an inhibitor of SREBP1, could increase the sensitivity of endometrial cancer to progesterone and reverse progesterone resistance by inhibiting SREBP1 both in vitro and in vivo. Our results highlight the important role of SREBP1 in progesterone resistance and suggest that the use of Fatostatin to target SREBP1 may represent a new method to solve progesterone resistance in patients with endometrial cancer.

Fatostatin in Combination with Tamoxifen Induces Synergistic Inhibition in ER-Positive Breast Cancer

Drug Des Devel Ther 2020 Aug 26;14:3535-3545.PMID:32921987DOI:10.2147/DDDT.S253876.

Background: Tamoxifen is the cornerstone of adjuvant therapy for hormone receptor-positive breast cancer. Despite its efficacy, limited drug sensitivity and endocrine resistance remain the important clinical challenges. The main objective of this study was to investigate Fatostatin, which was found to sensitize breast cancer to the antitumour effect of tamoxifen both in vitro and in vivo. Methods: Fatostatin-induced ER degradation was detected by immunoprecipitation assay. The antitumour effect of Fatostatin and tamoxifen on MCF-7 and T47D cells was assessed by MTT and colony forming assays. Cell cycle arrest was detected by flow cytometric analysis. Apoptosis was detected by annexin V/propidium iodide double staining and TUNEL assay. Autophagy was detected by MDC assay and acridine orange staining. Migration and invasion assays were performed using a Transwell system, and the efficacy of the synergistic use of Fatostatin and tamoxifen in vivo was evaluated using an MCF-7 xenograft model in BALB/c nu/nu female mice. Results: The synergistic use of Fatostatin and tamoxifen significantly suppressed cell viability and invasion, induced cell cycle arrest, and regulated apoptosis and autophagy in MCF-7 and T47D cell lines via PI3K-AKT-mTOR signalling. Additionally, the expression levels of Atg7/12/13, beclin and LC3B increased while p-mTOR and P62 expression levels decreased after treatment with Fatostatin and tamoxifen. Tumor growth in the xenograft model was suppressed significantly with the synergistic treatment of Fatostatin and tamoxifen. Conclusion: Fatostatin could induce ER degradation by K48-linked polyubiquitination, which was the key mechanism contributing to tamoxifen inhibition of PI3K-AKT-mTOR signalling in breast cancer. Fatostatin may have a promising clinical use for ER-positive breast cancer patients.

Targeting SREBP-2-Regulated Mevalonate Metabolism for Cancer Therapy

Front Oncol 2020 Aug 21;10:1510.PMID:32974183DOI:10.3389/fonc.2020.01510.

Recently, targeting metabolic reprogramming has emerged as a potential therapeutic approach for fighting cancer. Sterol regulatory element binding protein-2 (SREBP-2), a basic helix-loop-helix leucine zipper transcription factor, mainly regulates genes involved in cholesterol biosynthesis and homeostasis. SREBP-2 binds to the sterol regulatory elements (SREs) in the promoters of its target genes and activates the transcription of mevalonate pathway genes, such as HMG-CoA reductase (HMGCR), mevalonate kinase and other key enzymes. In this review, we first summarized the structure of SREBP-2 and its activation and regulation by multiple signaling pathways. We then found that SREBP-2 and its regulated enzymes, including HMGCR, FPPS, SQS, and DHCR4 from the mevalonate pathway, participate in the progression of various cancers, including prostate, breast, lung, and hepatocellular cancer, as potential targets. Importantly, preclinical and clinical research demonstrated that Fatostatin, statins, and N-BPs targeting SREBP-2, HMGCR, and FPPS, respectively, alone or in combination with other drugs, have been used for the treatment of different cancers. This review summarizes new insights into the critical role of the SREBP-2-regulated mevalonate pathway for cancer and its potential for targeted cancer therapy.

Fatostatin induces pro- and anti-apoptotic lipid accumulation in breast cancer

Oncogenesis 2018 Aug 24;7(8):66.PMID:30140005DOI:10.1038/s41389-018-0076-0.

Given the dependence of cancers on de novo lipogenesis, we tested the effect of Fatostatin, a small molecule thought to target this pathway by blocking activation of SREBP transcription factors, in breast cancer cell lines and xenograft tumors. We found that estrogen receptor (ER) positive cells were more sensitive to Fatostatin than ER negative cells and responded with cell cycle arrest and apoptosis. Surprisingly, we found that rather than inhibiting lipogenesis, Fatostatin caused an accumulation of lipids as a response to endoplasmic reticulum stress rather than inhibition of SREBP activity. In particular, ceramide and dihydroceramide levels increased and contributed to the apoptotic effects of Fatostatin. In addition, an accumulation of triacylglycerides (TAGs), particularly those containing polyunsaturated fatty acids (PUFAs), was also observed as a result of elevated diacylglycerol transferase activity. Blocking PUFA-TAG production enhanced the apoptotic effect of Fatostatin, suggesting that these lipids play a protective role and limit Fatostatin response. Together, these findings indicate that the ability of breast cancer cells to respond to Fatostatin depends on induction of endoplasmic reticulum stress and subsequent ceramide accumulation, and that limiting production of PUFA-TAGs may be therapeutically beneficial in specific tumor subtypes.