Fasentin
目录号 : GC43654
An inhibitor of glucose transport
Cas No.:392721-37-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Fasentin is an inhibitor of glucose transport. It partially inhibits glucose uptake in U937 and DU145 cells when used at concentrations ranging from 15 to 80 µM. Fasentin sensitizes PPC-1 prostate cancer and U937 leukemia cells, but not DU145 prostate cancer cells, to cell death induced by the Fas receptor activator CH-11 activating anti-Fas antibody (FAS). It also increases the expression of AspSyn and PCK2, genes associated with glucose deprivation, in PPC-1 cells and halts the cell cycle at the G0/G1 phase in U937 cells when used at concentrations of 50 and 40 µM, respectively.
| Cas No. | 392721-37-8 | SDF | |
| Canonical SMILES | ClC1=C(C(F)(F)F)C=C(NC(CC(C)=O)=O)C=C1 | ||
| 分子式 | C11H9ClF3NO2 | 分子量 | 279.6 |
| 溶解度 | DMSO : 100 mg/mL (357.60 mM; Need ultrasonic) | 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。 |
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| 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。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.5765 mL | 17.8827 mL | 35.7654 mL |
| 5 mM | 0.7153 mL | 3.5765 mL | 7.1531 mL |
| 10 mM | 0.3577 mL | 1.7883 mL | 3.5765 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。
Fasentin diminishes endothelial cell proliferation, differentiation and invasion in a glucose metabolism-independent manner
Sci Rep 2020 Apr 9;10(1):6132.PMID:32273578DOI:10.1038/s41598-020-63232-z.
The synthetic compound Fasentin has been described as a modulator of GLUT-1 and GLUT-4 transporters, thus inhibiting glucose uptake in some cancer cells. Endothelial glucose metabolism has been recently connected to angiogenesis and it is now an emerging topic in scientific research. Indeed, certain compounds with a known effect on glucose metabolism have also been shown to inhibit angiogenesis. In this work we tested the capability of Fasentin to modulate angiogenesis in vitro and in vivo. We show that Fasentin inhibited tube formation in endothelial cells by a mechanism that involves a negative effect on endothelial cell proliferation and invasion, without affecting other steps related to the angiogenic process. However, Fasentin barely decreased glucose uptake in human dermal microvascular endothelial cells and the GLUT-1 inhibitor STF-31 failed to inhibit tube formation in these cells. Therefore, this modulatory capacity on endothelial cells function exerted by Fasentin is most likely independent of a modulation of glucose metabolism. Taken together, our results show a novel biological activity of Fasentin, which could be evaluated for its utility in cancer and other angiogenesis-dependent diseases.
A novel inhibitor of glucose uptake sensitizes cells to FAS-induced cell death
Mol Cancer Ther 2008 Nov;7(11):3546-55.PMID:19001437DOI:10.1158/1535-7163.MCT-08-0569.
Evasion of death receptor ligand-induced apoptosis is an important contributor to cancer development and progression. Therefore, molecules that restore sensitivity to death receptor stimuli would be important tools to better understand this biological pathway and potential leads for therapeutic adjuncts. Previously, the small-molecule N-[4-chloro-3-(trifluoromethyl)phenyl]-3-oxobutanamide (Fasentin) was identified as a chemical sensitizer to the death receptor stimuli FAS and tumor necrosis factor apoptosis-inducing ligand, but its mechanism of action was unknown. Here, we determined that Fasentin alters expression of genes associated with nutrient and glucose deprivation. Consistent with this finding, culturing cells in low-glucose medium recapitulated the effects of Fasentin and sensitized cells to FAS. Moreover, we showed that Fasentin inhibited glucose uptake. Using virtual docking studies with a homology model of the glucose transport protein GLUT1, Fasentin interacted with a unique site in the intracellular channel of this protein. Additional chemical studies with other GLUT inhibitors and analogues of Fasentin supported a role for partial inhibition of glucose transport as a mechanism to sensitize cells to death receptor stimuli. Thus, Fasentin is a novel inhibitor of glucose transport that blocks glucose uptake and highlights a new mechanism to sensitize cells to death ligands.
GLUT1 and TUBB4 in Glioblastoma Could be Efficacious Targets
Cancers (Basel) 2019 Sep 5;11(9):1308.PMID:31491891DOI:10.3390/cancers11091308.
Glioblastoma multiforme (GBM) is the most aggressive and deadly brain tumor, portending a median 13-month survival even following gross total resection with adjuvant chemotherapy and radiotherapy. This prognosis necessitates improved therapies for the disease. A target of interest for novel chemotherapies is the Warburg Effect, which describes the tumor's shift away from oxidative phosphorylation towards glycolysis. Here, we elucidate GLUT1 (Glucose transporter 1) and one of its associated binding partners, TUBB4 (Tubulin 4), as potentially druggable targets in GBM. Using data mining approach, we demonstrate that GLUT1 is overexpressed as a function of tumor grade in astrocytoma's and that its overexpression is associated with poorer prognosis. Using both mass spectrometry performed on hGBM (human glioblastoma patient specimen) and in silico modeling, we show that GLUT1 interacts with TUBB4, and more accurately demonstrates GLUT1's binding with Fasentin. Proximity ligation assay (PLA) and immunoprecipitation studies confirm GLUT1 interaction with TUBB4. Treatment of GSC33 and GSC28 cells with TUBB4 inhibitor, CR-42-24, reduces the expression of GLUT1 however, TUBB4 expression is unaltered upon Fasentin treatment. Using human pluripotent stem cell antibody array, we demonstrate reduced levels of Oct3/4, Nanog, Sox2, Sox17, Snail and VEGFR2 (Vascular endothelial growth factor receptor 2) upon CR-42-24 treatment. Overall, our data confirm that silencing TUBB4 or GLUT1 reduce GSC tumorsphere formation, self-renewal and proliferation in vitro. These findings suggest GLUT1 and its binding partner TUBB4 as druggable targets that warrant further investigation in GBM.
Extracellular vesicle glucose transporter-1 and glycan features in monocyte-endothelial inflammatory interactions
Nanomedicine 2022 Jun;42:102515.PMID:35074500DOI:10.1016/j.nano.2022.102515.
Monocyte-induced endothelial cell inflammation is associated with multiple pathological conditions, and extracellular vesicles (EVs) are essential nanosized components of intercellular communication. EVs derived from endotoxin-stimulated monocytes were previously shown to carry pro-inflammatory proteins and RNAs. The role of glucose transporter-1 (GLUT-1) and glycan features in monocyte-derived EV-induced endothelial cell inflammation remains largely unexplored. This study demonstrates that EVs derived from endotoxin-stimulated monocytes activate inflammatory pathways in endothelial cells, which are partially attributed to GLUT-1. Alterations in glycan features and increased levels of GLUT-1 were observed in EVs derived from endotoxin-stimulated monocytes. Notably, inhibition of EV-associated GLUT-1, through the use of Fasentin, suppressed EV-induced inflammatory cytokines in recipient endothelial cells.
Elevation of Chemosensitivity of Lung Adenocarcinoma A549 Spheroid Cells by Claudin-2 Knockdown through Activation of Glucose Transport and Inhibition of Nrf2 Signal
Int J Mol Sci 2021 Jun 19;22(12):6582.PMID:34205320DOI:10.3390/ijms22126582.
Claudin-2 (CLDN2), a tight junctional protein, is involved in the chemoresistance in a three-dimensional spheroid culture model of human lung adenocarcinoma A549 cells. However, the mechanism has not been fully clarified. We found that the knockdown of CLDN2 expression by siRNA in the spheroid reduces the expression of glucose transporters and metabolic enzymes. In a two-dimensional culture model, the expression of these proteins was increased by glucose deprivation or Fasentin, an inhibitor of glucose transporter. In addition, the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant enzymes including heme oxygenase-1, NAD(P)H:quinone oxidoreductase-1, and a glutamate-cysteine ligase modifier subunit were increased by Fasentin. The fluorescence intensities of JC-1, a probe of mitochondrial membrane potential, and MitoROS 580, a probe of mitochondrial superoxide production, were increased by Fasentin. These results suggest that mitochondrial production of reactive oxygen species is increased by glucose deficiency. The knockdown of CLDN2 enhanced the flux of 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG), a fluorescent deoxyglucose derivative, in a transwell assay, and the accumulation of glucose and 2-NBDG in spheroid cells. The expression of Nrf2 was decreased by CLDN2 knockdown, which was inhibited by Fasentin and sulforaphane, a typical Nrf2 activator, in spheroid cells. The sensitivity of spheroid cells to doxorubicin, an anthracycline antitumor antibiotic, was enhanced by CLDN2 knockdown, which was inhibited by Fasentin and sulforaphane. We suggest that CLDN2 induces chemoresistance in spheroid cells mediated through the inhibition of glucose transport and activation of the Nrf2 signal.