SJ-MX3400
|
AP-III-a4
|
|
AP-III-a4 (also known as ENOblock) is a novel and potent small molecule inhibitor of enolase which is isolated by small molecule screening in a cancer cell assay to detect cytotoxic agents that function in hypoxic conditions, which has previously been shown to induce drug resistance. AP-III-a4 is the first, nonsubstrate analogue that directly binds to enolase and inhibits its activity (IC50=0.576 uM); inhibit cancer cell metastasis in vivo. In HCT116 cells, AP-III-a4 induces cell death under hypoxia, and inhibits cancer cell migration and invasion by down-regulation of AKT and Bcl-xL expression. In Huh7 hepatocytes and HEK kidney cells, AP-III-a4 induces glucose uptake and inhibits phosphoenolpyruvate carboxykinase (PEPCK) expression. Thus, ENOblock is the first reported enolase inhibitor that is suitable for biological assays. This new chemical tool may also be suitable for further study as a cancer and diabetes drug candidate.
|