Syrosingopine (Su 3118) is an orally active lactate transporters (MCT1/MCT4) dual inhibitor, which can reduce glycolysis and induce synthetic lethality in cancer cells when combine with metformin. Syrosingopine shows anti-hypertensive activity by depleting peripheral stores of norepinephrine[2].IC50 & Target: MCT1 and MCT4In Vitro: Syrosingopine (10 μM; 1, 3, 4 hours) causes accumulation of intracellular lactate after 1 hour and peaks at 4 hours, which lead to intracellular acidification in HeLa cells.
Syrosingopine (10 μM; 1, 2 hours) slows lactate efflux by inhibiting MCT4 and MCT1 in MCT1-KO and MCT4-KO HAP1 cells, respectively.
Syrosingopine (10-100 μM)-metformin combination induces synthetic lethality by inhibiting transport of lactate in HAP1 MCT1-KO cells.In Vivo: Syrosingopine (5 mg/kg; s.c.; once) shows anti-hypertensive activity which as low as the result after ganglionic blockade by depleting peripheral stores of norepinephrine[2].