KAN0438757
目录号 : GC36383
KAN0438757是一种有效的选择性代谢激酶PFKFB3抑制剂，IC50值为0.19 μM。
Cas No.:1451255-59-6
Sample solution is provided at 25 µL, 10mM.
KAN0438757 is a potent and selective inhibitor of the metabolic kinase PFKFB3 with an IC50 value of 0.19μM[1]. PFKFB3 is an enzyme that plays a key role in glycolysis and is overexpressed in a variety of cancer cells[2]. KAN0438757 can also act as a selective inhibitor of PFKFB4[3].
In vitro, treatment of HCT-116, HT-29, HUVECs and normal colon epithelial cells with KAN0438757 (10-100μM) for 48 h increased cell death in a dose-dependent manner, but had little effect on normal colon epithelial cells[4]. Treatment of non-small cell lung cancer A549 cells with KAN0438757 (1-100μM) for 24-72 h significantly reduced cell viability, inhibited cell colony formation and migration, and induced DNA damage[5]. KAN0438757 (0-5μM) was treated with rat nucleus pulposus primary cells (NPP) for 24-72 h, which reduced tumor necrosis factor-α (TNF-α)-induced extracellular matrix (ECM) degradation, regulated the abnormal glycolytic energy metabolism phenotype, and had no cytotoxicity [6].
In vivo, KAN0438757 (25mg/kg) was treated by intraperitoneal injection in two pancreatitis model mice, and decreased levels of amylase and apoptosis activity were observed in both mice, inhibiting the exacerbation of fatty acid ethyl ester-induced severe acute pancreatitis (FAEE-SAP) and caerulein-induced acute pancreatitis (CAE-AP) [7].
References:
[1]Gustafsson N M S, Färnegårdh K, Bonagas N, et al. Targeting PFKFB3 radiosensitizes cancer cells and suppresses homologous recombination[J]. Nature communications, 2018, 9(1): 3872.
[2]Jones B C, Pohlmann P R, Clarke R, et al. Treatment against glucose-dependent cancers through metabolic PFKFB3 targeting of glycolytic flux[J]. Cancer and Metastasis Reviews, 2022, 41(2): 447-458.
[3]Wang S, Bei Y, Tian Q, et al. PFKFB4 facilitates palbociclib resistance in oestrogen receptor‐positive breast cancer by enhancing stemness[J]. Cell Proliferation, 2023, 56(1): e13337.
[4]De Oliveira T, Goldhardt T, Edelmann M, et al. Effects of the novel PFKFB3 inhibitor KAN0438757 on colorectal cancer cells and its systemic toxicity evaluation in vivo[J]. Cancers, 2021, 13(5): 1011.
[5]Özdemir D, Saruhan S, Ağca C A. KAN0438757: a novel PFKFB3 inhibitor that induces programmed cell death and suppresses cell migration in non-small cell lung carcinoma cells[J]. 2023.
[6]Cao X, Wang X, Rong K, et al. Specific PFKFB3 inhibitor memorably ameliorates intervertebral disc degeneration via inhibiting NF-κB and MAPK signaling pathway and reprogramming of energy metabolism of nucleus pulposus cells[J]. Oxidative Medicine and Cellular Longevity, 2022.
[7]Ergashev A, Shi F, Liu Z, et al. KAN0438757, a novel PFKFB3 inhibitor, prevent the progression of severe acute pancreatitis via the Nrf2/HO-1 pathway in infiltrated macrophage[J]. Free Radical Biology and Medicine, 2024, 210: 130-145.
KAN0438757是一种有效的选择性代谢激酶PFKFB3抑制剂，IC50值为0.19 μM[1]。PFKFB3是一种在糖酵解中发挥关键作用的酶，并在多种癌细胞中过度表达[2]。KAN0438757也可以作为PFKFB4的选择性抑制剂[3]。
在体外，KAN0438757（10-100μM）处理HCT-116、HT-29、HUVECs和正常结肠上皮细胞48 h，剂量依赖性地增加了细胞死亡率，但对正常结肠上皮细胞的影响较小[4]。KAN0438757（1-100μM）处理非小细胞肺癌A549细胞24-72h，显著降低了细胞活力，抑制了细胞的集落形成、迁移，诱导了DNA损伤[5]。KAN0438757（0-5μM）处理大鼠髓核原代细胞（NPP）24-72h，减轻了肿瘤坏死因子-α（TNF-α）诱导的细胞外基质（ECM）降解，调节了糖酵解能量代谢表型的异常，且没有细胞毒性[6]。
在体内，KAN0438757（25 mg/kg）通过腹腔注射治疗两种胰腺炎模型小鼠，均观察到淀粉酶和细胞凋亡活性水平下降，抑制了脂肪酸乙酯诱导的重症急性胰腺炎（FAEE-SAP）和雨蛙素诱导的急性胰腺炎（CAE-AP）的恶化[7]。
Cell experiment [1]: | |
Cell lines | HCT-116、HT-29、HUVECs、normal colon epithelial cells |
Preparation method | Cells were seeded into 96-well plates. After 24 h of incubation, the medium was replaced with 100 μL of medium containing different concentrations of KAN0438757(10, 25, 50, 100μM). Cell death was assessed within 48h. |
Reaction Conditions | 10, 25, 50, 100μM; 48 h |
Applications | KAN0438757 dose-dependently increased the cell death rates of HCT-116, HT-29, HUVECs, and normal colon epithelial cells, with less effect on normal colon epithelial cells. |
Animal experiment [2]: | |
Animal models | Wild-type C57BL/6 male mice |
Preparation method | Wild-type C57BL/6 male mice (8 weeks old), weighing 20-25 g, were randomly divided into groups (n=5) and fasted for 12h. The CAE-AP group was intraperitoneally injected with KAN0438757 (25mg/kg)+caerulein, and the FAEE-SAP group was intraperitoneally injected with KAN0438757 (25 mg/kg)+fatty acid ethyl ester. |
Dosage form | 25mg/kg; i.p. |
Applications | KAN0438757 inhibited the amylase level and apoptotic activity in the FAEE-SAP and CAE-AP group mice. |
References: | |
| Cas No. | 1451255-59-6 | SDF | |
| Canonical SMILES | O=C(OCCO)C1=CC=C(NS(=O)(C2=CC(C3=CC(F)=CC=C3O)=CC=C2)=O)C=C1O | ||
| 分子式 | C21H18FNO7S | 分子量 | 447.43 |
| 溶解度 | DMSO: 130 mg/mL (290.55 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.235 mL | 11.1749 mL | 22.3499 mL |
| 5 mM | 0.447 mL | 2.235 mL | 4.47 mL |
| 10 mM | 0.2235 mL | 1.1175 mL | 2.235 mL |
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| 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 |
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| % 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。
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Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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