PFK-158
目录号 : GC19293
PFK-158 是一种有效的选择性 PFKFB3 抑制剂，通过减少癌细胞中葡萄糖的摄取、ATP 的产生、乳酸的释放以及诱导细胞凋亡和自噬，显示出广泛的抗肿瘤活性.PFK-158 在 EC 细胞中以剂量和时间依赖性方式抑制细胞活力。
Cas No.:1462249-75-7
Sample solution is provided at 25 µL, 10mM.
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PFK-158 is a potent and selective PFKFB3 inhibitor, which shows extensive anti-tumor activity by reducing the uptake of glucose in cancer cells, the production of ATP, the release of lactic acid and inducing apoptosis and autophagy[1].
PFK-158 suppressed cell viability in a dose- and time-dependent manner in EC cells. Co-treatment with PFK158 (5 μM) and CBPt led to a significant increase in the percentage of apoptotic cells in HEC-1B and ARK-2. Furthermore, Western blot analysis revealed that the active form of PARP was significantly increased upon co-treatment, compared to single treatment alone, further demonstrating that the combination treatment enhances cell apoptosis[2]
The efficacy of PFK158 alone and in combination with carboplatin (CBPt) was evaluated on primary tumor growth and metastasis in HeyA8MDR‐bearing nude mice i.p. A marked reduction of tumor growth was observed in the combination treatment.PFK-158 with CBPt significantly reduced ascites and reduced LDs in tumor tissue as seen by immunofluorescence and transmission electron microscopy compared to untreated mice[3]
References:
[1]. Gustafsson NMS, F?rneg?rdh K, et al. Targeting PFKFB3 radiosensitizes cancer cells and suppresses homologous recombination. Nat Commun. 2018 Sep 24;9(1):3872.
[2]. Xiao Y, Jin L, et al. Inhibition of PFKFB3 induces cell death and synergistically enhances chemosensitivity in endometrial cancer. Oncogene. 2021 Feb;40(8):1409-1424.
[3]. Mondal S, Roy D, et al. Therapeutic targeting of PFKFB3 with a novel glycolytic inhibitor PFK158 promotes lipophagy and chemosensitivity in gynecologic cancers. Int J Cancer. 2019 Jan 1;144(1):178-189.
PFK-158 是一种有效的选择性 PFKFB3 抑制剂，通过减少癌细胞中葡萄糖的摄取、ATP 的产生、乳酸的释放以及诱导细胞凋亡和自噬，显示出广泛的抗肿瘤活性[ 1].
PFK-158 在 EC 细胞中以剂量和时间依赖性方式抑制细胞活力。与 PFK158 (5 μM) 和 CBPt 共同处理导致 HEC-1B 和 ARK-2 中凋亡细胞的百分比显着增加。此外，蛋白质印迹分析显示，与单独的单一治疗相比，联合治疗后 PARP 的活性形式显着增加，进一步证明联合治疗可增强细胞凋亡[2]
PFK158 单独使用和与卡铂 (CBPt) 联合使用对 HeyA8MDR 荷瘤裸鼠 i.p. 原发性肿瘤生长和转移的疗效进行了评估。在联合治疗中观察到肿瘤生长显着减少。与未治疗的小鼠相比，PFK-158 与 CBPt 显着减少腹水并减少肿瘤组织中的 LDs[3] /p>
| Cell experiment [1]: | |
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Cell lines |
human Ovarian Cancer cell lines (HeyA8 and HeyA8MDR), Cervical cancer cell line (OV2008, C13) |
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Preparation Method |
Cells were treated with PFK158, carboplatin (CBPt), Paclitaxel (PTX) alone and in combination, and Phosphatidyl‐serine externalization was analyzed by double staining the cells with FITC‐Annexin V and PI. |
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Reaction Conditions |
10 µM PFK-158 for 24h. |
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Applications |
PFK-158 treatment sensitizes chemoresistant cells (C13) and induces cell death. The combined treatment of PFK158 and CBPt resulted in significant increase in apoptosis in C13 (45%) compared to OV2008 cells (24.6%). Similar analysis using a combination of PFK158 and PTX showed a marked increase in apoptosis in the HeyA8MDR (70%) cells compared to HeyA8 (48%), respectively. |
| Animal experiment [2]: | |
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Animal models |
Endometrial cancer (EC) mouse xenograft models |
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Preparation Method |
HEC-1B and ARK-2 cells were subcutaneously injected. Following the detection of palpable tumors, the mice were treated with vehicle, PFK158 alone 2×/week, carboplatin (CBPt) alone 1×/week, or both for 14 days. |
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Dosage form |
35mg/kg PFK-158, intraperitoneal(i.p.) injection |
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Applications |
A significant reduction of tumor growth, tumor volume and tumor weight was observed at day 28 in both PFK158 alone and combination groups. H&E staining results demonstrated that PFK158- and combination treatment significantly increased tumor necrosis compared to control |
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References: [1]. Mondal S, Roy D, et al. Therapeutic targeting of PFKFB3 with a novel glycolytic inhibitor PFK158 promotes lipophagy and chemosensitivity in gynecologic cancers. Int J Cancer. 2019 Jan 1;144(1):178-189. [2]. Xiao Y, Jin L, et al. Inhibition of PFKFB3 induces cell death and synergistically enhances chemosensitivity in endometrial cancer. Oncogene. 2021 Feb;40(8):1409-1424. |
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| Cas No. | 1462249-75-7 | SDF | |
| Canonical SMILES | O=C(C1=CC=NC=C1)/C=C/C2=NC3=CC(C(F)(F)F)=CC=C3C=C2 | ||
| 分子式 | C18H11F3N2O | 分子量 | 328.29 |
| 溶解度 | DMSO : ≥ 30 mg/mL (91.38 mM) | 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.0461 mL | 15.2304 mL | 30.4609 mL |
| 5 mM | 0.6092 mL | 3.0461 mL | 6.0922 mL |
| 10 mM | 0.3046 mL | 1.523 mL | 3.0461 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。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet