1462249-75-7

PFK158 is an inhibitor of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3; IC₅₀ = 137 nM for human recombinant PFKFB3). It inhibits PFKFB3 and glycolysis in Jurkat cells (IC₅₀s = 1.6 and 0.847 μM, respectively). PFK158 inhibits the growth of leukemia cells in vitro (IC₅₀ = 0.33 μM for Jurkat cells) and reduces tumor volume in CT-26 murine colon carcinoma syngeneic model and a BxPC-3 pancreatic cancer mouse xenograft model. PFK158 also enhances activity of the anti-CTLA-4 antibody in the B16/F10 mouse model of melanoma.

PFK-158 is a potent and selective PFKFB3 inhibitor with an IC50 value 137 nM. PFK-158 reduces glucose uptake, ATP production, lactate release, and induces apoptosis and autophagy in cancer cells. PFK-158 has broad anti-tumor activity. PFK-158 can also enhance Colistin's resistance to bacteria[1][2][3].

[1] Mondal S, et al. 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
[2] Zhang Y, et al. Synergistic Effect of Colistin Combined with PFK-158 against Colistin-Resistant Enterobacteriaceae. Antimicrob Agents Chemother. 2019 Jun 24;63(7). pii: e00271-19. DOI:10.1128/AAC.00271-19
[3] Pooran Chand, et al. Pfkfb3 inhibitor and methods of use as an anti-cancer therapeutic. WO2013148228A1.