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Purity: ≥98%
PFK-158 (formerly known as PFK158; ACT-PFK-158) is a first-in-class, potent and selective inhibitor of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFK-2/FBPase) isoform 3 (PFKFB3) with potential anticancer activity. In a phase I study, PFK-158 is presently being studied in patients with advanced solid tumors. This is the first inhibitor of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) to be tested in cancer patients through a clinical trial. PFK-158 is a novel cancer metabolism target that has never been studied in human clinical trials. It is a small molecule therapeutic candidate. In patients with advanced solid malignancies, it is presently being studied in a phase I study.
| Targets |
PFKFB3 (IC50 = 137 nM)
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| ln Vitro |
PFK-158 (10 µM ; 24 hours; OV2008 and C13 cells) plus carboplatin (CBPt; 77-453 μM) significantly increases apoptosis in C13 (45%) and OV2008 cells (24.6%)[1].
PFK-158 (0-10 µM ; 24 hours; C13 and HeyA8MDR cells) treatment causes levels of lipid droplets (LD), p-PFKFB3, and p-cPLA2 to decrease in a dose-dependent manner[1]. PFK-158 (10 μM; 24 hours) has combined with Cisplatin to produce synergistic anti-proliferative effects in vitro in C13 and HeyA8MDR cells as opposed to OV2008 and HeyA8, respectively[1]. PFK-158 (0‐10 μM; 24 h) treatment induces autophagy induction in both C13 and HeyA8MDR cells as evidenced by the dose-dependent downregulation of p62/SQSTM1 and upregulation of LC3BII. The number of LDs is also decreased by PFK-158 treatment[1]. |
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| ln Vivo |
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| Enzyme Assay |
It was investigated whether PFK158 treatment could modify lipid pathways because increased glucose utilization in cancer promotes lipogenesis at several levels13 and because it might be another factor contributing to chemoresistance. Findings revealed that the PFK158 treatment dramatically decreased the number of LDs in the C13 and HeyA8MDR cells (Figs. 4c and d), which had more LDs than the chemosensitive cells (Fig. 4a and b). Interestingly, LDs were decreased in C13 and HeyA8MDR cells when PFKFB3 was genetically downregulated (Fig. 4e and g). According to the data, PFK158 and cisplatin together have synergistic antiproliferative effects in vitro in C13 and HeyA8MDR cells as compared to OV2008 and HeyA8, respectively (Fig. S3A-C and E-G, Supporting Information). In vitro and in vivo, PFK158 treatment causes lipophagy and makes chemoresistant cells more susceptible to the cytotoxic effects of chemotherapy. Notably, the results also demonstrated that more resistant cells than sensitive ones exhibit PFK158-induced chemosensitivity to carboplatin, which can be reversed by blocking autophagy with BafA. To sum up, this is one of the first investigations demonstrating that PFK158, a particular inhibitor of PFKFB3, simultaneously targets the lipogenic and glycolytic pathways—two highly active pathways in cancer—and encourages lipophagy to impede tumor growth.
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| Cell Assay |
Cell Line: OV2008 and C13 cells
Concentration: 10 µM Incubation Time: 24 hours Result: Combined with Carboplatin (CBPt) treatment resulted in significant increase in apoptosis. |
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| Animal Protocol |
Female athymic nude mice (nu/nu) (5-6 weeks old) injected with HeyA8MDR cells[1]
15 mg/kg Intraperitoneal injection; once a week; for 4 weeks |
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| References |
| Molecular Formula |
C18H11F3N2O
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| Molecular Weight |
328.08
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| Exact Mass |
328.08
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| Elemental Analysis |
C, 65.85; H, 3.38; F, 17.36; N, 8.53; O, 4.87
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| CAS # |
1462249-75-7
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| Related CAS # |
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| Appearance |
Solid powder
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| SMILES |
C1=CC(=CC2=C1C=CC(=N2)/C=C/C(=O)C3=CC=NC=C3)C(F)(F)F
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| InChi Key |
IAJOMYABKVAZCN-AATRIKPKSA-N
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| InChi Code |
InChI=1S/C18H11F3N2O/c19-18(20,21)14-3-1-12-2-4-15(23-16(12)11-14)5-6-17(24)13-7-9-22-10-8-13/h1-11H/b6-5+
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| Chemical Name |
(E)-1-pyridin-4-yl-3-[7-(trifluoromethyl)quinolin-2-yl]prop-2-en-1-one
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2 mg/mL (6.09 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2 mg/mL (6.09 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2 mg/mL (6.09 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0480 mL | 15.2402 mL | 30.4804 mL | |
| 5 mM | 0.6096 mL | 3.0480 mL | 6.0961 mL | |
| 10 mM | 0.3048 mL | 1.5240 mL | 3.0480 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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