PFK-158

• CAS: 1462249-75-7
• Catalog Number: ACM1462249757
• Category: Inhibitors
• Molecular Weight: 328.29
• Molecular Formula: C18H11F3N2O
• Description: 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.
• Synonyms: PFK158; PFK 158; PFK158; ACTPFK158
• IUPAC Name: (E)-1-(pyridin-4-yl)-3-(7-(trifluoromethyl)quinolin-2-yl)prop-2-en-1-one
• Canonical SMILES: O=C(C1=CC=NC=C1)/C=C/C2=NC3=CC(C(F)(F)F)=CC=C3C=C2
• InChI: 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+
• InChI Key: IAJOMYABKVAZCN-AATRIKPKSA-N
• Solubility: Soluble in DMSO, not in water
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• 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.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 65.85; H, 3.38; F, 17.36; N, 8.53; O, 4.87
• Exact Mass: 328.08235
• HS Tariff Code: 2934.99.9001
• 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/
• Shipping: 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.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).