Background:

PFK-015 is a potent and selective inhibitor of PFKFB3 with IC50 value of 207 nM [1].

6-phosphofructo-2-kinase (PFKFB3) is an enzyme that is encoded by the PFKFB3 gene in humans. PFKFB3 is a direct transcriptional target of HIF-α and is activated by oncogenic AKT and Ras and stabilized by the loss of the tumor suppressor PTEN via suppressive effects on APC/Cdh1-mediated ubiquitination [1].

PFK-015 is a potent and selective PFKFB3 inhibitor. In H522 lung adenocarcinoma and Jurkat cell lines, PFK15 exhibited cytotoxic effects with IC50 values of 2.42 and 0.72 μM in Jurkat and H522, respectively. Also, PFK15 reduced glucose uptake, intracellular ATP and F26BP, the substrate of PFKFB3. In Jurkat T cell leukemia cells, PFK15 (3 μM) increased the number of cells undergoing early apoptosis. PFK15 (3 and 20 μM) increased the number of cells undergoing late apoptosis in a dose dependent way [1].

In Lewis lung carcinoma (LLC)-bearing mice, PFK15 inhibited LLC cells metastasized from the subcutaneous to the lungs. PFK15 decreased tumor-associated F26BP and significantly increased the number of cells that were positive for cleaved caspase 3. Also, PFK15 reduced fluoro-D-glucose (18F-FDG) uptake by 50%. PFK15 inhibited the growth of colon and pancreatic adenocarcinomas [1].

Reference:
[1].  Clem BF, O'Neal J, Tapolsky G, et al. Targeting 6-phosphofructo-2-kinase (PFKFB3) as a therapeutic strategy against cancer. Mol Cancer Ther, 2013, 12(8): 1461-1470.