PFK-015
目录号 : GC16993
PFK-015是一种高效、选择性的PFKFB3抑制剂，其IC₅₀值为110nM。
Cas No.:4382-63-2
Sample solution is provided at 25 µL, 10mM.
PFK-015 is a potent and selective inhibitor of PFKFB3 with an IC50 value of 110nM[1]. As a key regulator of glycolytic metabolism, PFK-015 disrupts fructose-2,6-bisphosphate production and demonstrates significant anti-proliferative effects across multiple tumor cell lines[2]. The compound also induces autophagy and exhibits synergistic activity with chemotherapeutic agents in vivo[3].
In Peripheral blood mononuclear cells treatment with PFK-015(10μM; 80min) during IFN-γ-induced macrophage polarization reduced the expression of M1 surface markers CD80, iNOS, and HLA-DR[4]. In the 786-O and OS-RC-2 cell lines, the expression levels of glycolytic regulatory enzymes, key enzymes, and PD-L1 decreased after the addition of the PFKFB3 inhibitor PFK-015(10μM; 24h)[5].
In Lewis lung carcinoma (LLC)-bearing mice, PFK-015(25mg/kg; iv; every 3 days for 4 doses） inhibits the growth of Lewis lung carcinoma (LLC) xenografts by mediating the depletion of tumor-associated fructose-2,6-bisphosphate (F26BP), which consequently triggers apoptotic signaling and suppresses pulmonary metastasis of the subcutaneous tumors[6]. In the Hu-NOG mouse model, PFK-015(25mg/kg; ip; 21d）combined with PD-1 mAb therapy significantly inhibits tumor growth in human PBMC-engrafted NOG mice[7].
References:
[1].Clem B, Tapolsky G H, O'Neal J, et al. Characterization of a novel small molecule antagonist of 6-phosphofructo-2-kinase that suppresses glucose metabolism and tumor growth[J]. Cancer Research, 2011, 71(8_Supplement): 2825-2825.
[2].Ling X, Liu L, Jiang A, et al. PFKFB3 promotes endometriosis cell proliferation via enhancing the protein stability of β-catenin[J]. Molecular and Cellular Endocrinology, 2024, 579: 112083.
[3].Brooke D G, van Dam E M, Watts C K W, et al. Targeting the Warburg Effect in cancer; relationships for 2-arylpyridazinones as inhibitors of the key glycolytic enzyme 6-phosphofructo-2-kinase/2, 6-bisphosphatase 3 (PFKFB3)[J]. Bioorganic & medicinal chemistry, 2014, 22(3): 1029-1039.
[4].Chen R, Wang J, Dai X, et al. Augmented PFKFB3-mediated glycolysis by interferon-γ promotes inflammatory M1 polarization through the JAK2/STAT1 pathway in local vascular inflammation in Takayasu arteritis[J]. Arthritis research & therapy, 2022, 24(1): 266.
[5].Yu Y, Liang Y, Li D, et al. Glucose metabolism involved in PD-L1-mediated immune escape in the malignant kidney tumour microenvironment[J]. Cell Death Discovery, 2021, 7(1): 15.
[6].Clem B F, O'Neal J, Tapolsky G, et al. Targeting 6-phosphofructo-2-kinase (PFKFB3) as a therapeutic strategy against cancer[J]. Molecular cancer therapeutics, 2013, 12(8): 1461-1470.
[7].Zheng J B, Wong C W, Liu J, et al. Glucose metabolism inhibitor PFK-015 combined with immune checkpoint inhibitor is an effective treatment regimen in cancer[J]. Oncoimmunology, 2022, 11(1): 2079182.
PFK-015是一种高效、选择性的PFKFB3抑制剂，其IC₅₀值为110nM[1]。作为糖酵解代谢的关键调节因子，PFK-015通过干扰果糖-2,6-二磷酸的生成，在多种肿瘤细胞系中表现出显著的抗增殖作用[2]。该化合物还能诱导细胞自噬，并在体内与化疗药物展现出协同抗肿瘤活性[3]。
在外周血单核细胞中，使用PFK-015（10μM；80min）处理可干扰IFN-γ诱导的巨噬细胞极化，降低M1型表面标志物CD80、iNOS和HLA-DR的表达[4]。在786-O和OS-RC-2细胞系中，加入PFKFB3抑制剂PFK-015（10μM；24h）后，糖酵解调节酶、关键酶及PD-L1的表达水平均有所下降[5]。
在Lewis肺癌荷瘤小鼠模型中，PFK-015（25mg/kg；iv；每3天一次，共4次）通过介导肿瘤相关果糖-2,6-二磷酸的耗竭，进而激活凋亡信号通路，抑制皮下移植瘤的生长并减少其肺转移[6]。在Hu-NOG小鼠模型中，PFK-015（25mg/kg；ip；21d）与PD-1单克隆抗体联合治疗，可显著抑制人源PBMC重建NOG小鼠中的肿瘤生长[7]。
| Cell experiment [1]: | |
Cell lines | Peripheral blood mononuclear cells |
Preparation Method | Peripheral blood mononuclear cells supplemented with 40ng/ml macrophage colony-stimulating factor (M-CSF) was used as a differentiation medium. To examine the role of PFKFB3 in macrophage polarization, PFKFB3 inhibitor PFK-015 (10μM) was used. |
Reaction Conditions | 10μM; 80min |
Applications | Treatment with PFK-015 during IFN-γ-induced macrophage polarization reduced the expression of M1 surface markers CD80, iNOS, and HLA-DR. |
| Animal experiment [2]: | |
Animal models | Xenograft modle |
Preparation Method | LL cells were obtained from DMEM medium containing 10% FCS in the exponential growth phase. After washing twice, the cells were resuspended in PBS buffer. 0.1mL of cell suspension (1×10⁶ cells) was subcutaneously injected into C57Bl6 mice. Mice carrying xenograft tumors (150–200mg) were randomly assigned to four groups: DMSO group, PFK-015 group (25mg/kg, intraperitoneal injection, every 3 days for 4 doses), irinotecan group (70mg/kg, intravenous injection, every 3 days for 4 doses), temozolomide group (30mg/kg, oral administration, 3 consecutive days followed by a 3-day break), and gemcitabine group (100mg/kg, every 3 days for 4 doses). Tumor size was measured daily using microcalipers. |
Dosage form | 25mg/kg; iv; every 3 days for 4 doses |
Applications | PFK-015 inhibits the growth of Lewis lung carcinoma (LLC) xenografts by mediating the depletion of tumor-associated fructose-2,6-bisphosphate (F26BP), which consequently triggers apoptotic signaling and suppresses pulmonary metastasis of the subcutaneous tumors. |
References: | |
| Cas No. | 4382-63-2 | SDF | |
| Canonical SMILES | O=C(C1=CC=NC=C1)/C([H])=C([H])/C2=NC3=CC=CC=C3C=C2 | ||
| 分子式 | C17H12N2O | 分子量 | 260.29 |
| 溶解度 | ≥ 13mg/mL in DMSO | 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 | 3.8419 mL | 19.2093 mL | 38.4187 mL |
| 5 mM | 768.4 μL | 3.8419 mL | 7.6837 mL |
| 10 mM | 384.2 μL | 1.9209 mL | 3.8419 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
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- Purity: >98.00%
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