PFK-158 |
Catalog No.GC19293
One-Click Copy Product Info
|
PFK-158 is a potent and selective inhibitor of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) (IC50=137nM).
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1462249-75-7
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
PFK-158 is a potent and selective inhibitor of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) (IC50=137nM). PFK-158 binds to and inhibits PFKFB3 activity, reduces fructose-2,6-bisphosphate levels, thereby suppressing cancer cell glycolysis and glucose uptake, decreasing ATP production and lactate release, and inducing apoptosis, autophagy and chemosensitization, exerting immunomodulatory effects on Th17 cells, γδT17 cells and myeloid-derived suppressor cells. PFK-158 can be used in research related to solid tumors including breast cancer, lung cancer, glioblastoma, ovarian cancer, pancreatic cancer, melanoma and colon cancer, as well as follicular lymphoma, in metabolism and oncology studies[1-4].
In vitro, treatment with PFK-158 (10nM-1μM) for 72h in multiple myeloma cells (RPMI8226, U266, MM.1S, MM.1R and bortezomib-resistant KMS-11/BTZ cells) inhibited myeloma cell proliferation, increased Caspase3/7 activity and decreased 20S proteasome activity[5]. Treatment with PFK-158 (1μM) in human retinal pigment epithelial cells (ARPE-19) immediately caused a decrease in electrical resistance and induced reversible barrier dysfunction[6]. Treatment with PFK-158 (0-20μM) for 24h in human small cell lung cancer cells (H1048, H1882, H1876 and DMS53 cells) dose-dependently inhibited cell proliferation, downregulated CSC markers Aldh1, CD133, CD44 and Sox2 expression, and promoted apoptosis[7].
In vivo, female ICR mice infected with Klebsiella pneumoniae H04 or Enterobacter cloacae D01 received an intravenous injection of PFK-158 at 15mg/kg combined with colistin 1 hour post-infection, PFK-158 improved survival rates of mice infected with K. pneumoniae H04 or E. cloacae D01 and significantly reduced bacterial loads in liver, spleen and kidney tissues[8]. Ldlr-/- mice on a high-fat cholesterol diet received intraperitoneal injections of PFK-158 at 2mg/kg three times per week for 5 weeks, PFK-158 reduced the incidence of aortic arch fibrous cap atheromas (advanced plaques), decreased necrotic core area and intra-plaque apoptosis, increased fibrous cap thickness and smooth muscle cell content, and improved plaque stability index[9]. Nu/nu mice subcutaneously inoculated with EMMeso cells in the right forelimb received intraperitoneal injections of PFK-158 at 30mg/kg twice per week for 2 weeks, PFK-158 reduced tumor burden, tumor volume and tumor weight[10].
References:
[1] Pan Y, Zhang Y, Laghari ZA, et al. PFK-158 enhances colistin efficacy against resistant Edwardsiella piscicida through synergistic mechanisms. Front Vet Sci. 2026 Feb 12;13:1748700.
[2] Wang W, Zhang YW, Hu SJ, et al. Design, synthesis, and antibacterial evaluation of PFK-158 derivatives as potent agents against drug-resistant bacteria. Bioorg Med Chem Lett. 2021 Jun 1;41:127980.
[3] Tan B, Zhang J, Dong K, et al. Neutrophil glycolysis mediates colitis-induced exacerbation of Alzheimer's disease. Int Immunopharmacol. 2026 Feb 15;171:116127.
[4] Jia W, Wu Q, Shen M, et al. PFKFB3 regulates breast cancer tumorigenesis and Fulvestrant sensitivity by affecting ERα stability. Cell Signal. 2024 Jul;119:111184.
[5] Okabe S, Tanaka Y, Gotoh A. Therapeutic targeting of PFKFB3 and PFKFB4 in multiple myeloma cells under hypoxic conditions. Biomarker Res. 2022 May 16;10:31.
[6] Naghdi A, Oska N, Yumnamcha T, et al. The significance of upper glycolytic components in regulating retinal pigment epithelial cellular behavior. Sci Rep. 2024 Aug 14;14:18862.
[7] Thirusangu P, Ray U, Sarkar Bhattacharya S, et al. PFKFB3 regulates cancer stemness through the hippo pathway in small cell lung carcinoma. Oncogene. 2022 Jul;41(36):4003-4017.
[8] Zhang Y, Wang X, Li X, et al. Synergistic effect of colistin combined with PFK-158 against colistin-resistant Enterobacteriaceae. Antimicrob Agents Chemother. 2019 Jul;63(7):e00271-19.
[9] Poels K, Schnitzler JG, Waissi F, et al. Inhibition of PFKFB3 Hampers the Progression of Atherosclerosis and Promotes Plaque Stability. Front Cell Dev Biol. 2020 Nov 12;8:581641.
[10] Sarkar Bhattacharya S, Thirusangu P, Jin L, et al. PFKFB3 inhibition reprograms malignant pleural mesothelioma to nutrient stress-induced macropinocytosis and ER stress as independent binary adaptive responses. Cell Death Dis. 2019 Sep 27;10(10):725.
| Cell experiment [1]: | |
|
Cell lines |
H1048 cells, H1882 cells, H1876 cells, DMS53 cells (human small cell lung carcinoma cell lines) |
|
Preparation Method |
SCLC cells were maintained in DMEM/F12 medium supplemented with 5% FBS at 37°C, 5% CO₂. Cells were treated with PFK-158 at 0-20μM for 24h in 2D culture or as CSC-enriched 3D spheroids, after which cell viability, spheroid/colony formation, glucose uptake (2-NBDG), LDH activity, ATP level, apoptosis (Annexin V/PI), CSC markers (Aldh1, CD133, CD44, Sox2), ABCG2, YAP/TAZ signaling (p-MST1, NF2, p-LATS1, nuclear/cytoplasmic YAP/TAZ), EMT markers (Twist, Snail, Vimentin, E-cadherin, p-FAK/total FAK) and chemosensitivity to doxorubicin/etoposide/5-FU were assessed. |
|
Reaction Conditions |
0-20μM; 24h |
|
Applications |
PFK-158 inhibited proliferation of H1048, H1882, H1876 and DMS53 cells in a dose-dependent manner and showed enhanced sensitivity in CSC-enriched spheroids. PFK-158 reduced spheroid number/size and colony formation. PFK-158 decreased 2-NBDG glucose uptake, LDH activity and intracellular ATP levels. PFK-158 increased Annexin V-positive apoptotic cells and cleaved PARP. PFK-158 downregulated Aldh1, CD133, CD44 and Sox2 in CSC-enriched cells. PFK-158 reduced ABCG2 expression. PFK-158 activated p-MST1 and NF2, increased p-LATS1(T1079), promoted cytoplasmic retention of YAP/TAZ and suppressed YAP/TAZ-TEAD transcriptional activity. PFK-158 downregulated Twist, Snail, Vimentin and p-FAK/total FAK while upregulating E-cadherin, and reduced migration/invasion. PFK-158 sensitized ABCG2high CSC cells to ABCG2-substrate drugs doxorubicin, etoposide and 5-FU. |
| Animal experiment [2]: | |
|
Animal models |
Female athymic homozygous nude mice (nu/nu, 4-8 weeks old) |
|
Preparation Method |
Mice were acclimated for 1 week, then randomized into 4 groups (n=6). EMMeso cells (5×106 in 200μL PBS) were subcutaneously injected into the right flank of the forelimb. Five days after inoculation, mice received treatment for 2 weeks: control (40% Captisol), PFK-158 at 30mg/kg intraperitoneally twice weekly, carboplatin at 50mg/kg intraperitoneally once weekly, or combination of carboplatin (50mg/kg once weekly) and PFK-158 (30mg/kg twice weekly). Mice were observed for 5 days after the 2-week treatment and sacrificed on day 21. Tumor volume, body weight and tumor weight were recorded; tumor lysates were analyzed by Western blot and IHC (p-PFKFB3, BiP, Ki67, Rac1), and tumors were examined by TEM. |
|
Dosage form |
30mg/kg; i.p.; twice weekly for 2 weeks |
|
Applications |
PFK-158 administration reduced tumor burden, tumor growth, tumor volume and tumor weight in EMMeso xenografts. PFK-158 decreased p-PFKFB3(S461) expression in tumor lysates and increased Rac1, Rab7 and BiP/Grp78 expression. PFK-158 reduced Ki67 staining in tumor sections. TEM of PFK-158-treated tumors showed profound methuotic vacuoles. |
References: [1] Thirusangu P, Ray U, Sarkar Bhattacharya S, et al. PFKFB3 regulates cancer stemness through the hippo pathway in small cell lung carcinoma. Oncogene. 2022 Aug;41(36):4003-4017. [2] Sarkar Bhattacharya S, Thirusangu P, Jin L, et al. PFKFB3 inhibition reprograms malignant pleural mesothelioma to nutrient stress-induced macropinocytosis and ER stress as independent binary adaptive responses. Cell Death Dis. 2019 Sep 27;10(10):725. | |
| Cas No. | 1462249-75-7 | SDF | |
| Canonical SMILES | O=C(C1=CC=NC=C1)/C=C/C2=NC3=CC(C(F)(F)F)=CC=C3C=C2 | ||
| Formula | C18H11F3N2O | M.Wt | 328.29 |
| Solubility | DMSO : ≥ 30 mg/mL (91.38 mM) | Storage | Store at -20°C |
| 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 | 3.0461 mL | 15.2304 mL | 30.4609 mL |
| 5 mM | 609.2 μL | 3.0461 mL | 6.0922 mL |
| 10 mM | 304.6 μL | 1.523 mL | 3.0461 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
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: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 5 reference(s) in Google Scholar.)