VB124 is an orally active, potent and selective MCT4 inhibitor. VB124 blocked lactate import (IC50 value of 8.6 nM) and export (IC50 value of 19 nM) in MDA-MB-231 cells. VB124 is selective for MCT4 over MCT1 and shows minimal MCT1 inhibitory activity in MCT1-expressing BT20 cells (IC50 value of 24 μM).

VB124 blocks lactate import (IC50 of 8.6 nM) and export (IC50 of 19 nM) in MDA-MB-231 cells engineered to express MCT4 as the sole major plasma membrane lactate transporter; VB124 is selective for MCT4 over MCT1 and shows minimal MCT1 inhibitory activity in MCT1-expressing BT20 cells (IC50 of 24 μM). [1]

METHODS: Mice were treated with a supramaximal dose of VB124 (30 mg/kg twice daily for 180 days) and the effects on body, heart, liver, or lung weights were observed.
RESULTS VB124 had no effect on body, heart, liver, or lung weights.
METHODS: Osmotic minipumps were surgically implanted to continuously deliver ISO to induce hypertrophy in mice, and these mice were simultaneously treated with VB124 (30 mg/kg) by daily oral gavage for 4 weeks. We performed echocardiography on these mice at the end of 4 weeks and collected their hearts after sacrifice.
RESULTS VB124 treatment ameliorated mitochondrial structural aberrations, and MCT4 inhibition reversed many of the pathological features of ISO-induced cardiac hypertrophy, including metabolic perturbations and mitochondrial structural damage. [1]