Syrosingopine is a dual inhibitor of MCT1 and MCT4, 60 times more potent against MCT4, preventing lactate and H+ efflux. Syrosingopine is an orally available antihypertensive drug with potential for cancer research in combination with metformin.

METHODS: Metformin, phenformin, and selected mitochondrial inhibitors were titrated in HL60 cells in the presence of a fixed concentration of syrosingopine (5 μM).
RESULTS Metformin sensitivity was altered approximately 15-fold in the presence of syrosingopine and 13-fold in the presence of phenformin.[1]
METHODS: MDA-MB-231 cells were treated with syrosingopine (1, 5, 10, 25, 50, 75, 10 μM) to evaluate the effects of syrosingopine treatment on the extracellular acidification rate (ECAR) and intracellular acidification in MDA-MB-231 cells.
RESULTS The extracellular acidification rate (ECAR) was significantly reduced in cells. The reduction in ECAR was stable over time and did not differ between 24 or 72 h of exposure. For the more oxidative FaDu model, a significant reduction in ECAR was observed after treatment with 25 μM syrosingopine; the pHi values ​​of MDA-MB-231 cells were 50 μM and the pHi values ​​of FaDu were 25 μM. [2]

METHODS: Tsc1−/Pten− liver knockout mice were treated with syrosingopine (7.5 mg/kg, intraperitoneally), metformin (200 mg/kg), or the combination on alternate days for a total of 6 treatments. The in vivo efficacy of the drug combination was tested in a mouse liver cancer model.
RESULTS After this short treatment, liver size and the number of visible tumor nodules were reduced; histological examination of liver sections showed a reduction in tumor burden. [1]