Syrosingopine

Syrosingopine has selective depleting effect on brain amines is potentiated by combined treatment with disulfiram or fusaric acid, a dopamine beta-hydroxylase inhibitor.The anticancer activity of the widely used diabetic drug metformin is strongly potentiated by Syrosingopine. Synthetic lethality elicited by combining the two drugs is synergistic and specific to transformed cells. This effect is unrelated to Syrosingopine s known role as an inhibitor of the vesicular monoamine transporters. Syrosingopine binds to the glycolytic enzyme α±-enolase in vitro, and the expression of the γ-enolase isoform correlates with nonresponsiveness to the drug combination. Syrosingopine sensitized cancer cells to metformin and its more potent derivative phenformin far below the individual toxic threshold of each compound.