PFK-158 | ACT- PFK-158 | CAS#1462249-75-7 | PFKFB3 Inhibitor

MedKoo Cat#: 206166 | Name: PFK-158

Description:

WARNING: This product is for research use only, not for human or veterinary use.

PFK-158, also known as ACT-PFK-158, is an inhibitor of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFK-2/FBPase) isoform 3 (PFKFB3) with potential antineoplastic activity. Upon administration, PFKFB3 inhibitor PFK-158 binds to and inhibits the activity of PFKFB3, which leads to the inhibition of both the glycolytic pathway in and glucose uptake by cancer cells. This prevents the production of macromolecules and energy that causes the enhanced cellular proliferation in cancer cells as compared to that of normal, healthy cells. Depriving cancer cells of nutrients and energy leads to the inhibition of cancer cell growth.

Chemical Structure

PFK-158

CAS#1462249-75-7

Theoretical Analysis

MedKoo Cat#: 206166

Name: PFK-158

CAS#: 1462249-75-7

Chemical Formula: C18H11F3N2O

Exact Mass: 328.0824

Molecular Weight: 328.29

Elemental Analysis: C, 65.85; H, 3.38; F, 17.36; N, 8.53; O, 4.87

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 750.00	Ready to ship

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Related CAS #

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Synonym

PFK158; PFK 158; PFK158; ACTPFK158.

IUPAC/Chemical Name

(E)-1-(pyridin-4-yl)-3-(7-(trifluoromethyl)quinolin-2-yl)prop-2-en-1-one

InChi Key

IAJOMYABKVAZCN-AATRIKPKSA-N

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+

SMILES Code

O=C(C1=CC=NC=C1)/C=C/C2=NC3=CC(C(F)(F)F)=CC=C3C=C2

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

The PFKFB enzymes (PFKFB 1- 4) synthesize fructose-2,6-bisphosphate (F2,6BP) which activates 6-phosphofructo-l- kinase (PFK-1), an essential control point in the glycolytic pathway. Neoplastic cells preferentially utilize glycolysis to satisfy their increased needs for energy and biosynthetic precursors. Malignant tumor cells have glycolytic rates that are up to 200 times higher than those of their normal tissues of origin. One cancer attack strategy has been to treat cancer by starving cancerous cells in various ways. Reducing or blocking the enhanced glycolytic flux mechanism present in cancer cells has stimulated recent interest. Despite greater understanding and pharmaceutical advances in the diagnosis and treatment of cancer, it is still estimated that nearly 13% of all human deaths last year were due to cancer. Thus, there remains a need for safe and effective anti-cancer therapeutics, particularly those which target neoplastic cells via mechanisms such as glycolytic flux, which are over-expressed in cancer cells. (http://www.google.com/patents/WO2013148228A1?cl=en)

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C22R10B09

View CoA: current batch, Lot#C8R04B10

QC Data

View QC data: current batch, Lot#C22R10B09

View QC data: current batch, Lot#C8R04B10

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

PFK-158 is a potent and selective PFKFB3 inhibitor that reduces glucose uptake, ATP production, lactate release, and induces apoptosis and autophagy in cancer cells. PFK-158 has an IC50 value of 137 nM.

In vitro activity:

Since elevated glucose utilization in cancer supports lipogenesis at multiple levels13 and considering that it could be another contributing factor toward chemoresistance, it was checked whether PFK158 treatment could modulate lipid pathways. Results showed that the C13 and HeyA8MDR cells had more LDs compared to the chemosensitive cells (Fig.4 a and b) and PFK158 treatment significantly reduced the number of LDs in these cells (Fig4 c and d). Of interest, genetic downregulation of PFKFB3 in C13 and HeyA8MDR cells (Fig.4 e and g) also resulted in a reduction of LDs. The data indicates that PFK158 has synergistic antiproliferative effects in vitro when combined with cisplatin in C13 and HeyA8MDR cells compared to OV2008 and HeyA8, respectively (Fig. S3A‐C and E‐G, Supporting Information). PFK158 treatment induces lipophagy and also sensitizes chemoresistant cells to chemotherapy‐induced cytotoxicity both in vitro and in vivo. Importantly, this data also showed that inhibiting autophagy with BafA reverses the PFK158‐induced chemosensitivity to carboplatin more in the resistant than the sensitive cells. In conclusion, this is one of the first studies to show that PFK158, a specific inhibitor of PFKFB3, simultaneously targets both the glycolytic and lipogenic pathways, two pathways that are very active in cancer, and promotes lipophagy to inhibit tumor growth. Int J Cancer. 2019 Jan 1;144(1):178-189. https://pubmed.ncbi.nlm.nih.gov/30226266/

In vivo activity:

PFK158 (Fig. (Fig.1b) obtained on an MTA from Gossamer Bio (San Diego, CA) was dissolved in 40% solution of Captisol in ddH2O for in vivo studies. To further investigate the activity of PFK158 alone and/or in combination with carboplatin (CBP) in an MPM xenograft nude mouse model, EMMeso cells were implanted subcutaneously in nude mice (Fig. S9A). A noticeable reduction in tumor burden (Fig. S9B and Fig.7a, tumor growth (Fig.7b), tumor volume (Fig.7c), and tumor weight (Fig.7d) were observed in both in PFK158 alone and in combination treatment. It was also observed that the tumor burden in PFK158-treated mice was significantly (P < 0.0002) less than the one in the vehicle-treated controls. However, the data also showed that the PFK158 alone was profoundly effective as it was in combination with CBP treatment in reducing pleural mesothelioma progression compared to CBP single treatment group Together the in vivo data revealed that PFK158-mediated inhibition of tumorigenesis occurs through methuosis and ER stress to reduce the tumor burden. Finally, PFK158 alone and in combination with carboplatin-inhibited tumorigenesis of EMMeso xenografts in vivo. Since most cancer cells exhibit an increased glycolytic rate, these results provide evidence for PFK158, in combination with standard chemotherapy, may have a potential in the treatment of MPM. This is the first study to establish that inhibition of PFKFB3 with a small molecule antagonist, PFK158; can introduce glycolytic assault which simultaneously triggers ER stress and methuosis and eventually suppress MPM cell growth both in vitro and in vivo (Fig.88). Cell Death Dis. 2019 Oct; 10(10): 725.Published online 2019 Sep 27. doi: 10.1038/s41419-019-1916-3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764980/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	14.0	42.60

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 328.29 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Mondal S, Roy D, Sarkar Bhattacharya S, Jin L, Jung D, Zhang S, Kalogera E, Staub J, Wang Y, Xuyang W, Khurana A, Chien J, Telang S, Chesney J, Tapolsky G, Petras D, Shridhar V. Therapeutic targeting of PFKFB3 with a novel glycolytic inhibitor PFK158 promotes lipophagy and chemosensitivity in gynecologic cancers. Int J Cancer. 2019 Jan 1;144(1):178-189. doi: 10.1002/ijc.31868. Epub 2018 Oct 30. Erratum in: Int J Cancer. 2019 Jul 15;145(2):E13. PMID: 30226266; PMCID: PMC6261695. 2. Sarkar Bhattacharya S, Thirusangu P, Jin L, Roy D, Jung D, Xiao Y, Staub J, Roy B, Molina JR, Shridhar V. 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. doi: 10.1038/s41419-019-1916-3. PMID: 31562297; PMCID: PMC6764980. 3. . Mondal S, Roy D, Sarkar Bhattacharya S, Jin L, Jung D, Zhang S, Kalogera E, Staub J, Wang Y, Xuyang W, Khurana A, Chien J, Telang S, Chesney J, Tapolsky G, Petras D, Shridhar V. Therapeutic targeting of PFKFB3 with a novel glycolytic inhibitor PFK158 promotes lipophagy and chemosensitivity in gynecologic cancers. Int J Cancer. 2019 Jan 1;144(1):178-189. doi: 10.1002/ijc.31868. Epub 2018 Oct 30. Erratum in: Int J Cancer. 2019 Jul 15;145(2):E13. PMID: 30226266; PMCID: PMC6261695. 4. Sarkar Bhattacharya S, Thirusangu P, Jin L, Roy D, Jung D, Xiao Y, Staub J, Roy B, Molina JR, Shridhar V. 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. doi: 10.1038/s41419-019-1916-3. PMID: 31562297; PMCID: PMC6764980.

In vitro protocol:

In vivo protocol:

1: Naghdi A, Oska N, Yumnamcha T, Eltanani S, Shawky M, Me R, Ibrahim AS. The significance of upper glycolytic components in regulating retinal pigment epithelial cellular behavior. Sci Rep. 2024 Aug 14;14(1):18862. doi: 10.1038/s41598-024-68343-5. PMID: 39143171; PMCID: PMC11324787. 2: Wang X, Liu X, Wu W, Liao L, Zhou M, Wang X, Tan Z, Zhang G, Bai Y, Li X, Zhao M. Hypoxia activates macrophage-NLRP3 inflammasome promoting atherosclerosis via PFKFB3-driven glycolysis. FASEB J. 2024 Aug 15;38(15):e23854. doi: 10.1096/fj.202400283R. PMID: 39096131. 3: Jia W, Wu Q, Shen M, Yu X, An S, Zhao L, Huang G, Liu J. PFKFB3 regulates breast cancer tumorigenesis and Fulvestrant sensitivity by affecting ERα stability. Cell Signal. 2024 Jul;119:111184. doi: 10.1016/j.cellsig.2024.111184. Epub 2024 Apr 17. PMID: 38640982. 4: Oska N, Eltanani S, Shawky M, Naghdi A, Gregory A, Yumnamcha T, Ibrahim AS. Upper glycolytic components contribute differently in controlling retinal vascular endothelial cellular behavior: Implications for endothelial-related retinal diseases. PLoS One. 2023 Nov 30;18(11):e0294909. doi: 10.1371/journal.pone.0294909. PMID: 38033124; PMCID: PMC10688887. 5: Yu H, Dai C, Zhu W, Jin Y, Wang C. PFKFB3 Increases IL-1β and TNF-α in Intestinal Epithelial Cells to Promote Tumorigenesis in Colitis- Associated Colorectal Cancer. J Oncol. 2022 Aug 16;2022:6367437. doi: 10.1155/2022/6367437. PMID: 36016583; PMCID: PMC9398832. 6: Guo S, Li A, Fu X, Li Z, Cao K, Song M, Huang S, Li Z, Yan J, Wang L, Dai X, Feng D, Wang Y, He J, Huo Y, Xu Y. Gene-dosage effect of Pfkfb3 on monocyte/macrophage biology in atherosclerosis. Br J Pharmacol. 2022 Nov;179(21):4974-4991. doi: 10.1111/bph.15926. Epub 2022 Aug 3. PMID: 35834356; PMCID: PMC10420406. 7: Thirusangu P, Ray U, Sarkar Bhattacharya S, Oien DB, Jin L, Staub J, Kannan N, Molina JR, Shridhar V. PFKFB3 regulates cancer stemness through the hippo pathway in small cell lung carcinoma. Oncogene. 2022 Aug;41(33):4003-4017. doi: 10.1038/s41388-022-02391-x. Epub 2022 Jul 8. Erratum in: Oncogene. 2023 Jan;42(1):79-82. doi: 10.1038/s41388-022-02470-z. PMID: 35804016; PMCID: PMC9374593. 8: Sarkar Bhattacharya S, Thirusangu P, Jin L, Staub J, Shridhar V, Molina JR. PFKFB3 works on the FAK-STAT3-SOX2 axis to regulate the stemness in MPM. Br J Cancer. 2022 Oct;127(7):1352-1364. doi: 10.1038/s41416-022-01867-7. Epub 2022 Jul 6. PMID: 35794237; PMCID: PMC9519537. 9: Okabe S, Tanaka Y, Gotoh A. Therapeutic targeting of PFKFB3 and PFKFB4 in multiple myeloma cells under hypoxic conditions. Biomark Res. 2022 May 16;10(1):31. doi: 10.1186/s40364-022-00376-2. PMID: 35578370; PMCID: PMC9109357. 10: Jiang YX, Siu MKY, Wang JJ, Leung THY, Chan DW, Cheung ANY, Ngan HYS, Chan KKL. PFKFB3 Regulates Chemoresistance, Metastasis and Stemness via IAP Proteins and the NF-κB Signaling Pathway in Ovarian Cancer. Front Oncol. 2022 Jan 28;12:748403. doi: 10.3389/fonc.2022.748403. PMID: 35155224; PMCID: PMC8837381. 11: Cargill KR, Stewart CA, Park EM, Ramkumar K, Gay CM, Cardnell RJ, Wang Q, Diao L, Shen L, Fan YH, Chan WK, Lorenzi PL, Oliver TG, Wang J, Byers LA. Targeting MYC-enhanced glycolysis for the treatment of small cell lung cancer. Cancer Metab. 2021 Sep 23;9(1):33. doi: 10.1186/s40170-021-00270-9. PMID: 34556188; PMCID: PMC8461854. 12: Chen L, Yu K, Chen L, Zheng X, Huang N, Lin Y, Jia H, Liao W, Cao J, Zhou T. Synergistic Activity and Biofilm Formation Effect of Colistin Combined with PFK-158 Against Colistin-Resistant Gram-Negative Bacteria. Infect Drug Resist. 2021 Jun 9;14:2143-2154. doi: 10.2147/IDR.S309912. PMID: 34135604; PMCID: PMC8200155. 13: Ray U, Roy D, Jin L, Thirusangu P, Staub J, Xiao Y, Kalogera E, Wahner Hendrickson AE, Cullen GD, Goergen K, Oberg AL, Shridhar V. Group III phospholipase A2 downregulation attenuated survival and metastasis in ovarian cancer and promotes chemo-sensitization. J Exp Clin Cancer Res. 2021 Jun 3;40(1):182. doi: 10.1186/s13046-021-01985-9. PMID: 34082797; PMCID: PMC8173968. 14: Wang W, Zhang YW, Hu SJ, Niu WP, Zhang GN, Zhu M, Wang MH, Zhang F, Li XM, Wang JX. 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. doi: 10.1016/j.bmcl.2021.127980. Epub 2021 Mar 22. PMID: 33766773. 15: Kotowski K, Rosik J, Machaj F, Supplitt S, Wiczew D, Jabłońska K, Wiechec E, Ghavami S, Dzięgiel P. Role of PFKFB3 and PFKFB4 in Cancer: Genetic Basis, Impact on Disease Development/Progression, and Potential as Therapeutic Targets. Cancers (Basel). 2021 Feb 22;13(4):909. doi: 10.3390/cancers13040909. PMID: 33671514; PMCID: PMC7926708. 16: Xiao Y, Jin L, Deng C, Guan Y, Kalogera E, Ray U, Thirusangu P, Staub J, Sarkar Bhattacharya S, Xu H, Fang X, Shridhar V. Inhibition of PFKFB3 induces cell death and synergistically enhances chemosensitivity in endometrial cancer. Oncogene. 2021 Feb;40(8):1409-1424. doi: 10.1038/s41388-020-01621-4. Epub 2021 Jan 8. PMID: 33420377; PMCID: PMC7906909. 17: Poels K, Schnitzler JG, Waissi F, Levels JHM, Stroes ESG, Daemen MJAP, Lutgens E, Pennekamp AM, De Kleijn DPV, Seijkens TTP, Kroon J. Inhibition of PFKFB3 Hampers the Progression of Atherosclerosis and Promotes Plaque Stability. Front Cell Dev Biol. 2020 Nov 12;8:581641. doi: 10.3389/fcell.2020.581641. PMID: 33282864; PMCID: PMC7688893. 18: Guan Y, Chen X, Wu M, Zhu W, Arslan A, Takeda S, Nguyen MH, Majeti R, Thomas D, Zheng M, Peltz G. The phosphatidylethanolamine biosynthesis pathway provides a new target for cancer chemotherapy. J Hepatol. 2020 Apr;72(4):746-760. doi: 10.1016/j.jhep.2019.11.007. Epub 2019 Nov 22. PMID: 31760071; PMCID: PMC7085447. 19: Sarkar Bhattacharya S, Thirusangu P, Jin L, Roy D, Jung D, Xiao Y, Staub J, Roy B, Molina JR, Shridhar V. 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. doi: 10.1038/s41419-019-1916-3. PMID: 31562297; PMCID: PMC6764980. 20: Zhang Y, Wang X, Li X, Dong L, Hu X, Nie T, Lu Y, Lu X, Pang J, Li G, Yang X, Li C, You X. Synergistic Effect of Colistin Combined with PFK-158 against Colistin-Resistant Enterobacteriaceae. Antimicrob Agents Chemother. 2019 Jun 24;63(7):e00271-19. doi: 10.1128/AAC.00271-19. PMID: 30988150; PMCID: PMC6591609.