The comet assay revealed severe DNA damage (Tail DNA, fold change, untreated cell; 1, CUR-20 µM; 1.2, KAN-20 µM; 3, and COMB; 4.6) in the A549 cells, while MMP analysis (color change from red to green) and apoptotic staining confirmed cell death morphologically (color change from green to orange). Moreover, Western blot analysis demonstrated that the combination markedly enhanced apoptosis in the A549 cells.

The LC/MS metabolic profile of A-498 cells treated under identical conditions with the known PFKFB3 inhibitor, PFK158, was distinct from that induced by B2. These results thus demonstrate the identification and validation of a new PFKFB kinase inhibitor.

Our findings demonstrate that PFKFB3 is crucial for PARPi resistance in OC. Inhibiting PFKFB3 sensitizes HR-proficient OC cells to PARPis by impairing HR repair, leading to increased DNA damage and apoptosis. PFKFB3 represents a promising therapeutic target for overcoming PARPi resistance and improving outcomes in OC patients.

Additionally, in vivo neoadjuvant treatment with 3PO induced TVN, alleviated tumor hypoxia and increased tumor necrosis. Our results support PFKFB3 inhibition as a possible future neoadjuvant addition for rectal cancer patients.

PFKFB3 can enhance ATC cell proliferation and migration via the WNT/β-catenin signaling pathway and plays a crucial role in the regulation of aerobic glycolysis in ATC cells.

The combined administration of Lomitapide and Gemcitabine at a certain molar ratio indicated an enhanced anti-tumor effect in Orthotopic Pancreatic Cancer (OPC) models. This investigation provides a new treatment strategy for PC therapy.

In summary, our present in vitro study demonstrated that 3PO derived PFK15 mechanism of action is totally different from AZ67 in TNBC cells. However, we advocate that the PFK15-mediated inhibition (along with PFKL) on the TNBCs migration, colony formation, and PFK-1 activity can be further explored for the therapeutic advantage of TNBC patients.

Previously, we demonstrated that BAPTA enhanced apoptosis induced by venetoclax, a BCL-2 antagonist, in diffuse large B-cell lymphoma (DLBCL)...In this study, we discovered that BAPTA alone induced apoptosis in hematological cancer cell lines that were highly sensitive to S63845, an MCL-1 antagonist...Secondly, cellular effects caused by BAPTA are not necessarily related to Ca signaling. Our data support the need for a reassessment of the role of Ca in cellular processes when findings were based on the use of BAPTA.

KAN0438757 showed a clear antiproliferative effect in rectal cancer cells and PDX without being overly toxic in vivo. It showed promis- ing synergistic efficacy when used in combination with chemotherapy and therefore should be further tested in vivo.

This study confers a comprehensive and mechanistic function of PFKFB3 in CSC maintenance that may foster exceptional opportunities for targeted small molecule blockade of the TICs in MPM.