Aldometanib (Iodide)

Aldometanib is an inhibitor of aldolase (IC₅₀ = ~15 nM for lysosome-bound aldolase) and an activator of AMP-activated protein kinase (AMPK).¹ It selectively activates lysosomal AMPK over cytosolic or mitochondrial AMPK at 5 nM. Aldometanib (50 µM) inhibits ferroptosis in H9c2 cardiomyocytes in an in vitro model of myocardial ischemia-reperfusion injury.² It decreases blood glucose levels in lean mice, decreases blood glucose levels, fat mass, and hepatic lipid accumulation in high-fat diet-induced obese mice, and increases lifespan and healthspan in aged mice.¹ Aldometanib (5 mg/kg) inhibits glycolysis, increases survival, and decreases disease progression in a mouse model of amyotrophic lateral sclerosis (ALS).³ It increases intratumoral CD8⁺ T cell infiltration in models of hepatocellular carcinoma (HCC) using immunocompetent but not immunodeficient mice.⁴

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1. Zhang, C.S., Li, M., Y., W., et al. The aldolase inhibitor aldometanib mimics glucose starvation to activate lysosomal AMPK. Nat. Metab. 4(10), 1369-1401 (2022).

2. Xie, M., Hao, J., Chao, C., et al. Aldometanib attenuates OGD/R-induced cardiomyocyte injury via mitigation of mitochondrial dysfunction. Tissue Cell 99, 103294 (2026).

3. Yan, K., Jiang, Y., Yong, Y., et al. ALDOA promotes glycolysis and NLRP3/GSDMD pyroptosis to accelerate ALS progression. Ann. Clin. Transl. Neurol. (2026).

4. Hu, H.H., Wang, X., Lan, B., et al. Glucose starvation mimetic aldometanib removes immune barriers permitting mice with hepatocellular carcinoma to live to normal ages. Cell Res. 934-953 (2025).