3PO |
| Catalog No.GC15118 |
3PO is a small-molecule inhibitor of PFKFB3, a key enzyme involved in glycolysis with IC50 values ranging from 1.4 to 24µM and a Ki value of 25 ± 9μM
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 18550-98-6
Sample solution is provided at 25 µL, 10mM.
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3PO is a small-molecule inhibitor of PFKFB3, a key enzyme involved in glycolysis with IC50 values ranging from 1.4 to 24µM and a Ki value of 25 ± 9μM. By inhibiting PFKFB3, 3PO reduces the levels of Fru-2,6-BP, lactate, ATP, NAD+, and NADH within cells[1]. 3PO has gained significant attention for its potential applications in cancer research and metabolic studies[2][3][4][5][6][7].
In vitro, 3PO (10µM) treated bladder cancer cells lines (5637, HT1197, HT1376, RT4, SW780, T24, TCCSUP, and UM-UC-3) for 72h reduced cell growth and also decreased lactate production and acidification of the culture medium, indicating its inhibitory effects on glycolysis[2]. 3PO (20μM) pretreatment of HUVEC for 30 min significantly reduced IKKα/β and JNK phosphorylation, thereby inhibiting inflammatory signaling induced by subsequent TNF (1ng/mL) or IL-1β (1ng/mL) stimulation[3]. 3PO (0.1–1.0µg/mL) incubated human umbilical vein endothelial cells (HUVECs) for 24, 48, or 72h reduce the ATP flow by cutting down the energy transform, thereby inhibiting tumor angiogenesis and assisting ROS to promote the early withering of tumor cells[4].
In vivo, 3PO (38-50mg/kg) injected intraperitoneally into choroidal neovascularization (CNV) mouse model amplified the antiangiogenic activity and dose dependently reduced the CNV lesion volume[5]. 3PO (150mg/kg) administered via intraperitoneal injection in mouse model after myocardial infarction (MI) once every other day for 28 days effectively reduced fibrosis and improved adverse cardiac remodeling[6]. 3PO in the cross-linked sodium lipoic acid vesicle (3PO@cLANa) (156.3mg/kg, containing 1.5mg/kg 3PO) administrated into B16F10 melanoma tumor model via intratumoral injection at days 1, 4, and 7 exerted antitumor and antimetastasis effects[7].
References:
[1] Clem B, Telang S, Clem A, et al. Small-molecule inhibition of 6-phosphofructo-2-kinase activity suppresses glycolytic flux and tumor growth.Mol Cancer Ther. 2008 Jan;7(1):110-20.
[2] Lea M A, Altayyar M, desBordes C. Inhibition of Growth of Bladder Cancer Cells by 3-(3-Pyridinyl)-1-(4-pyridinyl)-2-propen-1-one in Combination with Other Compounds Affecting Glucose Metabolism.Anticancer Res. 2015 Nov;35(11):5889-99.
[3] Wik J A, Peter Lundbäck P, Poulsen C L,et al. 3PO inhibits inflammatory NFκB and stress-activated kinase signaling in primary human endothelial cells independently of its target PFKFB3. PLoS One. 2020 Mar 4;15(3):e0229395.
[4] Li S Y, Ding H, Chang J H, et al. Sm/Co-Doped Silica-Based Nanozymes Reprogram Tumor Microenvironment for ATP-Inhibited Tumor Therapy.Adv Healthc Mater. 2023 Sep; 12(24):e2300652.
[5] Schoors S, Bock K D, Cantelmo A R, et al. Partial and transient reduction of glycolysis by PFKFB3 blockade reduces pathological angiogenesis.Cell Metab. 2014 Jan 7;19(1):37-48.
[6] Yang Q, Zong X, Zhuang L F, et al. PFKFB3 Inhibitor 3PO Reduces Cardiac Remodeling after Myocardial Infarction by Regulating the TGF-β1/SMAD2/3 Pathway. Biomolecules. 2023 Jul 3;13(7):1072.
[7] Lai H J, Wu X, Tan J.et al. Regulation of tumor lactate metabolism by targeting glycolysis and mitochondrial OXPHOS for tumor metastasis inhibition. J.Industrial & Engineering Chemistry Research. 2023 June,62(27)
| Kinase experiment [1]: | |
Preparation Method | Control reactions for 3PO inhibition contained increasing amounts of 3PO without addition of PFKFB3. The enzyme kinetics module for SigmaPlot 9.0 was used to calculate the kinetic variables for PFKFB3 and 3PO inhibition (Vmax, Km, and Ki). |
Reaction Conditions | 60, 100, and 150μmol/L |
Applications | 3PO inhibited PFKFB3 activity in a dose-dependent manner, with a Ki value of 25 ± 9μM. The inhibition was found to be mixed, involving both competitive and uncompetitive mechanisms. |
| Cell experiment [2]: | |
Cell lines | Human bladder cancer cell |
Preparation Method | Human bladder cancer cell lines, namely 5637, HT1197, HT1376, RT4, SW780, T24, TCCSUP and UM-UC-3 were incubated at 37˚C in RPMI-1640 medium with 5% fetal calf serum. A total of 5×103 cells were plated in 0.2ml of medium in 96-well plates. After allowing the cells to attach for 24h, the medium was changed with addition of control medium or medium containing drugs 5 or 10µM 3PO with or without presence of 1mM butyrate. Cells were incubated for a further 72h before growth determination and measurements on the medium. |
Reaction Conditions | 5 or 10µM; 72h |
Applications | 3PO exerted inhibitory effects on the growth of bladder cancer cells. 3PO treatment reversed the increased acidification of the medium and increased glucose uptake. |
| Animal experiment [3]: | |
Animal models | C57BL/6 mice |
Preparation Method | Choroidal neovascularization (CNV) was induced in C57BL/6 mice by laser burn. Mice were injected intraperitoneally (i.p.) with 38–50mg/kg PFKFB3 inhibitor 3PO daily with or without treatment with anti-VEGFR2 DC101 (12.5mg/kg, i.p.). Starting from 1 day after laser burn injury. Quantify CNV lesions upon injection with fluorescein isothiocyanate (FITC)-conjugated dextran at 14 days after laser injury. |
Dosage form | 38–50mg/kg; i.p.; daily for 2 weeks |
Applications | 3PO dose dependently reduced the choroidal neovascularization (CNV) lesion volume. 3PO also caused a decrease of CNV by 67% with the combination of DC101 (12.5mg/kg, i.p.), while DC101 treatment alone caused only 38% reduction. |
References: | |
| Cas No. | 18550-98-6 | SDF | |
| Chemical Name | (E)-3-(pyridin-3-yl)-1-(pyridin-4-yl)prop-2-en-1-one | ||
| Canonical SMILES | O=C(C1=CC=NC=C1)/C=C/C2=CN=CC=C2 | ||
| Formula | C13H10N2O | M.Wt | 210.23 |
| Solubility | DMF: 5 mg/mL,DMSO: 25 mg/mL,DMSO:PBS (pH 7.2) (1:10): 0.09 mg/mL,Ethanol: 2 mg/mL | 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 | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 4.7567 mL | 23.7835 mL | 47.567 mL |
| 5 mM | 0.9513 mL | 4.7567 mL | 9.5134 mL |
| 10 mM | 0.4757 mL | 2.3783 mL | 4.7567 mL |
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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 ddH2O, 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.
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Quality Control & SDS
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- Purity: >98.00%
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Average Rating: 5 (Based on Reviews and 18 reference(s) in Google Scholar.)
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