KAN0438757 |
Catalog No.GC36383
One-Click Copy Product Info
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KAN0438757 is a potent and selective inhibitor of the metabolic kinase PFKFB3 with an IC50 value of 0.19μM.
Products are for research use only. Not for human use. We do not sell to patients.
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.
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 | ||
| Formula | C21H18FNO7S | M.Wt | 447.43 |
| Solubility | DMSO: 130 mg/mL (290.55 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.235 mL | 11.1749 mL | 22.3499 mL |
| 5 mM | 447 μL | 2.235 mL | 4.47 mL |
| 10 mM | 223.5 μL | 1.1175 mL | 2.235 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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μL
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 10 reference(s) in Google Scholar.)