Syrosingopine

Syrosingopine is a dual inhibitor of MCT1 and MCT4, which are monocarboxylate transporters involved in lactate/H⁺ ion transport across the cell membrane.

Originally used as an antihypertensive drug (a reserpine analog).

Not a new compound — has been repurposed for anticancer research due to its metabolic effects.

GBM cells rely heavily on aerobic glycolysis (Warburg effect), producing high amounts of lactate.

MCT1 and MCT4 help export lactate out of tumor cells, preventing intracellular acidification and maintaining tumor growth and invasion.

Inhibiting MCT1/4 with syrosingopine disrupts this lactate export, leading to:

Acidic stress inside tumor cells

Impaired energy metabolism

Cell death

In U87MG and LN229 glioma cell lines:

Syrosingopine caused dose-dependent cytotoxicity

Induced apoptosis

Reduced cell migration and invasion

🔹 Advantages Good CNS penetration (essential for GBM therapy).

Previously used in humans for hypertension — known safety profile.

Potential combination therapy: prior studies suggest synergy with metformin or other metabolic inhibitors. ¹⁾